Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation.  Typically, immune cells detect the antigen presented on major histocompatibility complex (MHC) on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction.  They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

NK cells can be identified by the presence of CD56 and the absence of CD3 (CD56+, CD3−). NK cells differentiate from CD127+ common innate lymphoid progenitor, which is downstream of the common lymphoid progenitor from which B and T lymphocytes are also derived. NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation. NK cells differ from natural killer T cells (NKTs) phenotypically, by origin and by respective effector functions; often, NKT cell activity promotes NK cell activity by secreting interferon gamma. In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD57 in humans, NK1.1 or NK1.2 in C57BL/6 mice. The NKp46 cell surface marker constitutes, at the moment, another NK cell marker of preference being expressed in both humans, several strains of mice (including BALB/c mice) and in three common monkey species.

In addition to natural killer cells being effectors of innate immunity, both activating and inhibitory NK cell receptors play important functional roles, including self tolerance and the sustaining of NK cell activity.  NK cells also play a role in the adaptive immune response: numerous experiments have demonstrated their ability to readily adjust to the immediate environment and formulate antigen-specific immunological memory, fundamental for responding to secondary infections with the same antigen.  The role of NK cells in both the innate and adaptive immune responses is becoming increasingly important in research using NK cell activity as a potential cancer therapy and HIV therapy .

Early history
In early experiments on cell-mediated cytotoxicity against tumor target cells, both in cancer patients and animal models, investigators consistently observed what was termed a "natural" reactivity; that is, a certain population of cells seemed to be able to lyse tumor cells without having been previously sensitized to them. The first published study to assert that untreated lymphoid cells were able to confer a natural immunity to tumors was performed by Dr. Henry Smith at the University of Leeds School of Medicine in 1966, leading to the conclusion that the "phenomenon appear[ed] to be an expression of defense mechanisms to tumor growth present in normal mice." Other researchers had also made similar observations, but as these discoveries were inconsistent with the established model at the time, many initially considered these observations to be artifacts.

By 1973, 'natural killing' activity was established across a wide variety of species, and the existence of a separate lineage of cells possessing this ability was postulated. The discovery that a unique type of lymphocyte was responsible for "natural" or spontaneous cytotoxicity was made in the early 1970s by doctoral student Rolf Kiessling and postdoctoral fellow Hugh Pross, in the mouse,  and by Hugh Pross and doctoral student Mikael Jondal in the human.  The mouse and human work was carried out under the supervision of professors Eva Klein and Hans Wigzell, respectively, of the Karolinska Institute, Stockholm. Kiessling's research involved the well-characterized ability of T lymphocytes to lyse tumor cells against which they had been previously immunized. Pross and Jondal were studying cell-mediated cytotoxicity in normal human blood and the effect of the removal of various receptor-bearing cells on this cytotoxicity. Later that same year, Ronald Herberman published similar data with respect to the unique nature of the mouse effector cell.
The human data were confirmed, for the most part, by West et al.  using similar techniques and the same erythroleukemic target cell line, K562. K562 is highly sensitive to lysis by human NK cells and, over the decades, the K562  51chromium-release assay has become the most commonly used assay to detect human NK functional activity.  Its almost universal use has meant that experimental data can be compared easily by different laboratories around the world.

Using discontinuous density centrifugation, and later monoclonal antibodies, natural killing ability was mapped to the subset of large, granular lymphocytes known today as NK cells. The demonstration that density gradient-isolated large granular lymphocytes were responsible for human NK activity, made by Timonen and Saksela in 1980, was the first time that NK cells had been visualized microscopically, and was a major breakthrough in the field.

NK cell subsets
NK cells can be classified as CD56bright or CD56dim. CD56bright NK cells are similar to T helper cells in exerting their influence by releasing cytokines. CD56bright NK cells constitute the majority of NK cells, being found in bone marrow, secondary lymphoid tissue, liver, and skin. CD56bright NK cells are characterized by their preferential killing of highly proliferative cells, and thus might have an immunoregulatory role. CD56dim NK cells are primarily found in the peripheral blood, and are characterized by their cell killing ability. CD56dim NK cells are always CD16 positive (CD16 is the key mediator of antibody-dependent cellular cytotoxicity (ADCC). CD56bright can transition into CD56dim by acquiring CD16.

NK cells can eliminate virus-infected cells via CD16-mediated ADCC. All coronavirus disease 2019 (COVID-19) patients show depleted CD56bright NK cells, but CD56dim is only depleted in patients with severe COVID-19.

NK cell receptors

NK cell receptors can also be differentiated based on function. Natural cytotoxicity receptors directly induce apoptosis (cell death) after binding to Fas ligand that directly indicate infection of a cell. The MHC-independent receptors (described above) use an alternate pathway to induce apoptosis in infected cells. Natural killer cell activation is determined by the balance of inhibitory and activating receptor stimulation. For example, if the inhibitory receptor signaling is more prominent, then NK cell activity will be inhibited; similarly, if the activating signal is dominant, then NK cell activation will result.

NK cell receptor types (with inhibitory, as well as some activating members) are differentiated by structure, with a few examples to follow:

Activating receptors
Ly49 (homodimers),  relatively ancient, C-type lectin family receptors, are of multigenic presence in mice, while humans have only one pseudogenic Ly49, the receptor for classical (polymorphic) MHC I molecules.
NCR (natural cytotoxicity receptors), type 1 transmembrane proteins of the immunoglobulin superfamily, upon stimulation mediate NK killing and release of IFNγ. They bind viral ligands such as hemagglutinins and hemagglutinin neuraminidases, some bacterial ligands and cellular ligands related to tumour growth such as PCNA.
CD16 (FcγIIIA) plays a role in antibody-dependent cell-mediated cytotoxicity; in particular, they bind Immunoglobulin G.
TLR – Toll-like receptors are receptors that belong in the group of Pattern recognition receptors (PRR) which are typical for the cells of innate immunity but are expressed also on NK cells. They recognize PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) as their ligands. These receptors are crucial for the induction of the immune respose. TLR induction amplifies the immune response by promoting the production of inflammatory cytokines and chemokines and ultimately leads to the activation of NK cell effector functions. So NK cells directly reacts to the presence of pathogens in its surroundings. Apart from TLR-10 NK cells express all of the human TLR although in various levels. NK cells express high levels of TLR-1, moderate levels of TLR-2, TLR-3, TLR-5 and TLR-9, low levels of TLR-4, TLR-8 and TLR-9 and very low levels of TLR-7. TLR receptors are constitutialy expressed independently of their state of activation and they cooperate with cytokines and chemokines on the activation of the Natural Killer cells. These receptors are expressed extracellulary on the cell surface or endosomaly inside the endosomes. Apart from TLR-3 and TLR-4, all TLR signal through adaptor protein MyD88 which ultimately leads mainly to the activation of NF-κB. TLR-3 signals through the adaptor protein TRIF and TLR-4 can switch between signaling through MyD88 and TRIF respectively. Induction of different TLR leads to distinct activation of NK cell functions.

Inhibitory receptors
Killer-cell immunoglobulin-like receptors (KIRs) belong to a multigene family of more recently evolved Ig-like extracellular domain receptors; they are present in nonhuman primates, and are the main receptors for both classical MHC I (HLA-A, HLA-B, HLA-C) and nonclassical Mamu-G (HLA-G) in primates. Some KIRs are specific for certain HLA subtypes. Most KIRs are inhibitory and dominant. Regular cells express MHC class 1, so are recognised by KIR receptors and NK cell killing is inhibited.
 CD94/NKG2 (heterodimers), a C-type lectin family receptor, is conserved in both rodents and primates and identifies nonclassical (also nonpolymorphic) MHC I molecules such as HLA-E. Expression of HLA-E at the cell surface is dependent on the presence of nonamer peptide epitope derived from the signal sequence of classical MHC class I molecules, which is generated by the sequential action of signal peptide peptidase and the proteasome. Though indirect, this is a way to survey the levels of classical (polymorphic) HLA molecules.
ILT or LIR (immunoglobulin-like receptor) — are recently discovered members of the Ig receptor family.
 Ly49 (homodimers) have both activating and inhibitory isoforms. They are highly polymorphic on the population level; though they are structurally unrelated to KIRs, they are the functional homologues of KIRs in mice, including the expression pattern. Ly49s are receptor for classical (polymorphic) MHC I molecules.

Function

Cytolytic granule mediated cell apoptosis
NK cells are cytotoxic; small granules in their cytoplasm contain proteins such as perforin and proteases known as granzymes. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell, creating an aqueous channel through which the granzymes and associated molecules can enter, inducing either apoptosis or osmotic cell lysis. The distinction between apoptosis and cell lysis is important in immunology: lysing a virus-infected cell could potentially release the virions, whereas apoptosis leads to destruction of the virus inside. α-defensins, antimicrobial molecules, are also secreted by NK cells, and directly kill bacteria by disrupting their cell walls in a manner analogous to that of neutrophils.

Antibody-dependent cell-mediated cytotoxicity (ADCC)
Infected cells are routinely opsonized with antibodies for detection by immune cells.  Antibodies that bind to antigens can be recognised by FcγRIII (CD16) receptors expressed on NK cells, resulting in NK activation, release of cytolytic granules and consequent cell apoptosis. This is a major killing mechanism of some monoclonal antibodies like rituximab (Rituxan),  ofatumumab (Azzera), and others. The contribution of antibody-dependent cell-mediated cytotoxicity to tumor cell killing can be measured with a specific test that uses NK-92, an immortal line of NK-like cells licensed to NantKwest, Inc.: the response of NK-92 cells that have been transfected with a high-affinity Fc receptor are compared to that of the "wild type" NK-92 which does not express the Fc receptor.

Cytokine-induced NK and Cytotoxic T lymphocyte (CTL) activation
Cytokines play a crucial role in NK cell activation. As these are stress molecules released by cells upon viral infection, they serve to signal to the NK cell the presence of viral pathogens in the affected area. Cytokines involved in NK activation include IL-12, IL-15, IL-18, IL-2, and CCL5. NK cells are activated in response to interferons or macrophage-derived cytokines. They serve to contain viral infections while the adaptive immune response generates antigen-specific cytotoxic T cells that can clear the infection. NK cells work to control viral infections by secreting IFNγ and TNFα. IFNγ activates macrophages for phagocytosis and lysis, and TNFα acts to promote direct NK tumor cell killing.  Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection. [Citation needed]

Missing 'self' hypothesis

For NK cells to defend the body against viruses and other pathogens, they require mechanisms that enable the determination of whether a cell is infected or not. The exact mechanisms remain the subject of current investigation, but recognition of an "altered self" state is thought to be involved. To control their cytotoxic activity, NK cells possess two types of surface receptors:  activating receptors and inhibitory receptors, including killer-cell immunoglobulin-like receptors. Most of these receptors are not unique to NK cells and can be present in some T cell subsets, as well.

The inhibitory receptors recognize MHC class I alleles, which could explain why NK cells preferentially kill cells that possess low levels of MHC class I molecules. This mode of NK cell target interaction is known as "missing-self recognition", a term coined by Klas Kärre and co-workers in the late 90s. MHC class I molecules are the main mechanism by which cells display viral or tumor antigens to cytotoxic T cells. A common evolutionary adaptation to this is seen in both intracellular microbes and tumors: the chronic down-regulation of MHC I molecules, which makes affected cells invisible to T cells, allowing them to evade T cell-mediated immunity. NK cells apparently evolved as an evolutionary response to this adaptation (the loss of the MHC eliminates CD4/CD8 action, so another immune cell evolved to fulfill the function).

Tumor cell surveillance
Natural killer cells often lack antigen-specific cell surface receptors, so are part of innate immunity, i.e. able to react immediately with no prior exposure to the pathogen.  In both mice and humans, NKs can be seen to play a role in tumor immunosurveillance by directly inducing the death of tumor cells (NKs act as cytolytic effector lymphocytes), even in the absence of surface adhesion molecules and antigenic peptides. This role of NK cells is critical to immune success particularly because T cells are unable to recognize pathogens in the absence of surface antigens.  Tumor cell detection results in activation of NK cells and consequent cytokine production and release.

If tumor cells do not cause inflammation, they will also be regarded as self and will not induce a T cell response. A number of cytokines are produced by NKs, including tumor necrosis factor α (TNFα), IFNγ, and interleukin (IL-10). TNFα and IL-10 act as proinflammatory and immunosuppressors, respectively. The activation of NK cells and subsequent production of cytolytic effector cells impacts macrophages, dendritic cells, and neutrophils, which subsequently enables antigen-specific T and B cell responses. Instead of acting via antigen-specific receptors, lysis of tumor cells by NK cells is mediated by alternative receptors, including NKG2D, NKp44, NKp46, NKp30, and DNAM. NKG2D is a disulfide-linked homodimer which recognizes a number of ligands, including ULBP and MICA, which are typically expressed on tumor cells. The role of dendritic cell—NK cell interface in immunobiology have been studied and defined as critical for the comprehension of the complex immune system.

NK cells, along with macrophages and several other cell types, express the Fc receptor (FcR) molecule (FC-gamma-RIII = CD16), an activating biochemical receptor that binds the Fc portion of IgG class antibodies. This allows NK cells to target cells against which a humoral response has been gone through and to lyse cells through antibody-dependant cytotoxicity (ADCC). This response depends on the affinity of the Fc receptor expressed on NK cells, which can have high, intermediate, and low affinity for the Fc portion of the antibody. This affinity is determined by the amino acid in position 158 of the protein, which can be phenylalanine (F allele) or valine (V allele). Individuals with high-affinity FcRgammRIII (158 V/V allele) respond better to antibody therapy. This has been shown for lymphoma patients who received the antibody Rituxan. Patients who express the 158 V/V allele had a better antitumor response. Only 15–25% of the population expresses the 158 V/V allele. To determine the ADCC contribution of monoclonal antibodies, NK-92 cells (a "pure" NK cell line) has been transfected with the gene for the high-affinity FcR.

Clearance of senescent cells
Natural killer cells (NK cells) and macrophages play a major role in clearance of senescent cells. Natural killer cells directly kill senescent cells, and produce cytokines which activate macrophages which remove senescent cells.

Natural killer cells can use NKG2D receptors to detect senescent cells, and kill those cells using perforin pore-forming cytolytic protein. CD8+ cytotoxic T-lymphocytes also use NKG2D receptors to detect senescent cells, and promote killing similar to NK cells. For example, in patients with Parkinson's disease, levels of Natural killer cells are elevated as they degrade alpha-synuclein aggregates, destroy senescent neurons, and attenuate the neuroinflammation by leukocytes in the central nervous system.

Adaptive features of NK cells—"memory-like", "adaptive" and memory NK cells

The ability to generate memory cells following a primary infection and the consequent rapid immune activation and response to succeeding infections by the same antigen is fundamental to the role that T and B cells play in the adaptive immune response.  For many years, NK cells have been considered to be a part of the innate immune system. However, recently increasing evidence suggests that NK cells can display several features that are usually attributed to adaptive immune cells (e.g. T cell responses) such as dynamic expansion and contraction of subsets, increased longevity and a form of immunological memory, characterized by a more potent response upon secondary challenge with the same antigen.
In mice, the majority of research was carried out with murine cytomegalovirus (MCMV) and in models of hapten-hypersensitivity reactions. Especially, in the MCMV model, protective memory functions of MCMV-induced NK cells were discovered
and direct recognition of the MCMV-ligand m157 by the receptor Ly49 was demonstrated to be crucial for the generation of adaptive NK cell responses.
In humans, most studies have focused on the expansion of an NK cell subset carrying the activating receptor NKG2C (KLRC2). Such expansions were observed primarily in response to human cytomegalovirus (HCMV), but also in other infections including Hantavirus, Chikungunya virus, HIV, or viral hepatitis. However, whether these virus infections trigger the expansion of adaptive NKG2C+ NK cells or whether other infections result in re-activation of latent HCMV (as suggested for hepatitis
), remains a field of study. Notably, recent research suggests that adaptive NK cells can use the activating receptor NKG2C (KLRC2) to directly bind to human cytomegalovirus-derived peptide antigens and respond to peptide recognition with activation, expansion, and differentiation, a mechanism of responding to virus infections that was previously only known for T cells of the adaptive immune system.

NK cell function in pregnancy
As the majority of pregnancies involve two parents who are not tissue-matched, successful pregnancy requires the mother's immune system to be suppressed. NK cells are thought to be an important cell type in this process. These cells are known as "uterine NK cells" (uNK cells) and they differ from peripheral NK cells. They are in the CD56bright NK cell subset, potent at cytokine secretion, but with low cytotoxic ability and relatively similar to peripheral CD56bright NK cells, with a slightly different receptor profile. These uNK cells are the most abundant leukocytes present in utero in early pregnancy, representing about 70% of leukocytes here, but from where they originate remains controversial.

These NK cells have the ability to elicit cell cytotoxicity in vitro, but at a lower level than peripheral NK cells, despite containing perforin. Lack of cytotoxicity in vivo may be due to the presence of ligands for their inhibitory receptors. Trophoblast cells downregulate HLA-A and HLA-B to defend against cytotoxic T cell-mediated death. This would normally trigger NK cells by missing self recognition; however, these cells survive. The selective retention of HLA-E (which is a ligand for NK cell inhibitory receptor NKG2A) and HLA-G (which is a ligand for NK cell inhibitory receptor KIR2DL4) by the trophoblast is thought to defend it against NK cell-mediated death.

Uterine NK cells have shown no significant difference in women with recurrent miscarriage compared with controls. However, higher peripheral NK cell percentages occur in women with recurrent miscarriages than in control groups.

NK cells secrete a high level of cytokines which help mediate their function. NK cells interact with HLA-C to produce cytokines necessary for trophoblastic proliferation. Some important cytokines they secrete include TNF-α, IL-10, IFN-γ, GM-CSF and TGF-β, among others. For example, IFN-γ dilates and thins the walls of maternal spiral arteries to enhance blood flow to the implantation site.

NK cell evasion by tumor cells
By shedding decoy NKG2D soluble ligands, tumor cells may avoid immune responses.  These soluble NKG2D ligands bind to NK cell NKG2D receptors, activating a false NK response and consequently creating competition for the receptor site.  This method of evasion occurs in prostate cancer.  In addition, prostate cancer tumors can evade CD8 cell recognition due to their ability to downregulate expression of MHC class 1 molecules. This example of immune evasion actually highlights NK cells' importance in tumor surveillance and response, as CD8 cells can consequently only act on tumor cells in response to NK-initiated cytokine production (adaptive immune response).

Excessive NK cells
Experimental treatments with NK cells have resulted in excessive cytokine production, and even septic shock. Depletion of the inflammatory cytokine interferon gamma reversed the effect.

Applications

Anticancer therapy

Tumor-infiltrating NK cells have been reported to play a critical role in promoting drug-induced cell death in human triple-negative breast cancer. Since NK cells recognize target cells when they express nonself HLA antigens (but not self), autologous (patients' own) NK cell infusions have not shown any antitumor effects. Instead, investigators are working on using allogeneic cells from peripheral blood, which requires that all T cells be removed before infusion into the patients to remove the risk of graft versus host disease, which can be fatal. This can be achieved using an immunomagnetic column (CliniMACS). In addition, because of the limited number of NK cells in blood (only 10% of lymphocytes are NK cells), their number needs to be expanded in culture. This can take a few weeks and the yield is donor-dependent.

CAR-NK cells
Chimeric antigen receptors (CARs) are genetically modified receptors targeting cell surface antigens that provide a valuable approach to enhance effector cell efficacy. CARs induce high-affinity binding of effector cells carrying this receptor to cells expressing the target antigen, thereby lowering the threshold for cellular activation and inducing effector functions.

CAR T cells are now a fairly well-known cell therapy. However, wider use is limited by several fundamental problems: The high cost of CAR T cell therapy, which is due to the need to generate specific CAR T cells for each patient; the necessity to use only autologous T cells, due to the high risk of GvHD if allogeneic T cells are used; the inability to reinfuse CAR T cells if the patient relapses or low CAR T cell survival is observed; CAR T therapy also has a high toxicity, mainly due to IFN-γ production and subsequent induction of CRS (cytokine release syndrome) and/or neurotoxicity.

The use of CAR NK cells is not eliminated by the need to generate patient-specific cells, and at the same time, GvHD is not caused by NK cells, thus obviating the need for autologous cells. Toxic effects of CAR T therapy, such as CSR, have not been observed with the use of CAR NK cells. Thus, NK cells are considered an interesting "off-the-shelf" product option. Compared to CAR T cells, CAR NK cells retain unchanged expression of NK cell activating receptors. Thus, NK cells recognize and kill tumor cells even if, due to a tumor-escape strategy on tumor cells, ligand expression for the CAR receptor is downregulated.

NK cells derived from umbilical cord blood have been used to generate CAR.CD19 NK cells. These cells are capable of self-producing the cytokine IL-15, thereby enhancing autocrine/paracrine expression and persistence in vivo. Administration of these modified NK cells is not associated with the development of CSR, neurotoxicity, or GvHD.

The FT596 product is the first "Off-the-Shelf", universal, and allogenic CAR NK cellular product derived from iPSCs to be authorized for use in clinical studies in the USA. It consists of an anti-CD19 CAR optimized for NK cells with a transmembrane domain for the NKG2D activation receptor, a 2B4 costimulatory domain and a CD3ζ signaling domain. Two additional key components were added. A high-affinity, non-cleavable Fc receptor CD16 (hnCD16) that enables tumor targeting and enhanced antibody-dependent cell cytotoxicity without negative regulation, combined with a therapeutic monoclonal antibody targeting tumor cells and an IL-15/IL-15 receptor fusion protein (IL-15RF) promoting cytokine-independent persistence.

NK-92 cells
A more efficient way to obtain high numbers of NK cells is to expand NK-92 cells, an NK cell line with all the characteristics of highly active blood Natural Killer (NK) cells but with much broader and higher cytotoxicity. NK-92 cells grow continuously in culture and can be expanded to clinical-grade numbers in bags or bioreactors. Clinical studies have shown NK-92 cells to be safe and to exhibit anti-tumor activity in patients with lung or pancreatic cancer, melanoma, and lymphoma.  Because NK-92 cells originated from a patient with lymphoma, they must be irradiated prior to infusion. although efforts are being made to engineer the cells to eliminate the need for irradiation. The irradiated cells maintain full cytotoxicity. NK-92 are allogeneic (from a donor different from the recipient), but in clinical studies have not been shown to elicit significant host reaction.

Unmodified NK-92 cells lack CD-16, making them unable to perform antibody-dependent cellular cytotoxicity (ADCC); however, the cells have been engineered to express a high affinity Fc-receptor (CD16A, 158V) genetically linked to IL-2 that is bound to the endoplasmic reticulum (ER). These high affinity NK-92 cells can perform ADCC and have greatly expanded therapeutic utility.

NK-92 cells have also been engineered to expressed chimeric antigen receptors (CARs), in an approach similar to that used for T cells. An example of this is an NK-92 derived cell engineered with both a CD16 and an anti-PD-L1 CAR; currently in clinical development for oncology indications  A clinical grade NK-92 variant that expresses a CAR for HER2 (ErbB2) has been generated  and is in a clinical study in patients with HER2 positive glioblastoma. Several other clinical grade clones have been generated expressing the CARs for PD-L1, CD19, HER-2, and EGFR. PD-L1 targeted high affinity NK cells have been given to a number of patients with solid tumors in a phase I/II study, which is underway.

NKG2D-Fc Fusion Protein
In a study at Boston Children's Hospital, in coordination with Dana–Farber Cancer Institute, in which immunocompromised mice had contracted lymphomas from EBV infection, an NK-activating receptor called NKG2D was fused with a stimulatory Fc portion of the EBV antibody.  The NKG2D-Fc fusion proved capable of reducing tumor growth and prolonging survival of the recipients.  In a transplantation model of LMP1-fueled lymphomas, the NKG2D-Fc fusion proved capable of reducing tumor growth and prolonging survival of the recipients.

In Hodgkin lymphoma, in which the malignant Hodgkin Reed-Sternberg cells are typically HLA class I deficient, immune evasion is in part mediated by skewing towards an exhausted PD-1hi NK cell phenotype, and re-activation of these NK cells appears to be one mechanism of action induced by checkpoint-blockade.

TLR ligands
Signaling through TLR can effectively activate NK cell effector functions in vitro and in vivo. TLR ligands are than potentialy able to enhance NK cell effector functions during NK cell anti-tumor immunotherapy.

Trastuzumab is a monoclonal anti-HER2 antibody that is used as a treatment of the HER2+ breast cancer. NK cells are important part of the therapeutical effect of trastzumab as NK cells recognize the antibody coated cancer cells which induces ADCC (antibody-dependent cellular cytotoxicity) reaction. TLR ligand is used as a in addition to trastuzumab as a means to enhance its effect. The polysaccharide krestin, which is extracted from Trametes versicolor, is a potent ligand of TLR-2 and so activates NK cells, induses the production of IFNg and enhances the ADCC caused by regognition of trastuzumab coated cells.

Stimulation of TLR-7 induces the expression of IFN type I and other pro-inflammatory cytokines like IL-1b, IL-6 and IL-12. Mice suffering with NK cell-sensitive lymphoma RMA-S were treated with SC1 molecule. SC1 is novel small-molecule TLR-7 agonist and it´s repeated administration reportedly activated NK cells in TLR-7- and IFN type I- dependent manner thus reversing the NK cell anergy which ultimately lead to lysis of the tumor.

VTX-2337 is a selective TLR-8 agonist and together with monoclonal antibody cetuximab it was used as a potential therapy for the treatment of recurrent or metastatic SCCHN. The results show that NK cells has become more reactive to the treatment with cetuximab antibody upon pretreatment with VTX-2337. This indicates that the stimulation of TLR-8 and subsequent activation of inflammasome enhances the CD-16 mediated ADCC reaction in patients treated with cetuximab antibody.

NK cells play a role in controlling HIV-1 infection. TLR are potent enhancers of innate antiviral immunity and potentially can reverse HIV-1 latency. Incubation of peripheral blood mononuclear cells with novel potent TLR-9 ligand MGN1703 have resulted in enhancement of NK cell effector functions thus significalntly inhibiting the spread of HIV-1 in culture of autologous CD4+ T-cells. The stimulation of TLR-9 in NK cells induced strong antiviral innate immune response, the increase in HIV-1 transcription (indicating the reverse in latency of the virus) and it also boosted the NK cell-mediated suppression of HIV-1 infections in autologous CD4+ T cells.

New findings

Innate resistance to HIV
Recent research suggests specific KIR-MHC class I gene interactions might control innate genetic resistance to certain viral infections, including HIV and its consequent development of AIDS. Certain HLA allotypes have been found to determine the progression of HIV to AIDS; an example is the HLA-B57 and HLA-B27 alleles, which have been found to delay progression from HIV to AIDS. This is evident because patients expressing these HLA alleles are observed to have lower viral loads and a more gradual decline in CD4+ T cells numbers.  Despite considerable research and data collected measuring the genetic correlation of HLA alleles and KIR allotypes, a firm conclusion has not yet been drawn as to what combination provides decreased HIV and AIDS susceptibility.

NK cells can impose immune pressure on HIV, which had previously been described only for T cells and antibodies. HIV mutates to avoid NK cell detection.

Tissue-resident NK cells
Most of our current knowledge is derived from investigations of mouse splenic and human peripheral blood NK cells. However, in recent years tissue-resident NK cell populations have been described. These tissue-resident NK cells share transcriptional similarity to tissue-resident memory T cells described previously. However, tissue-resident NK cells are not necessarily of the memory phenotype, and in fact, majority of the tissue-resident NK cells functionally immature. These specialized NK-cell subsets can play a role in organ homeostasis. For example, NK cells are enriched in the human liver with a specific phenotype and take part in the control of liver fibrosis. Tissue-resident NK cells have also been identified in sites like bone marrow, spleen and more recently, in lung, intestines and lymph nodes. In these sites, tissue-resident NK cells may act as reservoir for maintaining immature NK cells in humans throughout life.

Adaptive NK cells against leukemia targets
Natural killer cells are being investigated as an emerging treatment for patients with acute myeloid leukemia (AML), and cytokine-induced memory-like NK cells have shown promise with their enhanced antileukemia functionality. It has been shown that this kind of NK cell has enhanced interferon-γ production and cytotoxicity against leukemia cell lines and primary AML blasts in patients. During a phase 1 clinical trial, five out of nine patients exhibited clinical responses to the treatment, and four patients experienced a complete remission, which suggests that these NK cells have major potential as a successful translational immunotherapy approach for patients with AML in the future.

See also
 Active hexose correlated compound
 Granzymes
 Hematopoiesis
 Immune system
 Interleukin
 Lymphatic system
 List of distinct cell types in the adult human body

References

Further reading

External links

Human cells
Immune system
Lymphocytes

Natural killer cell


"Bed" is a song by American singer J. Holiday serving as the second single for his debut studio album, Back of My Lac'. It was released by Capitol Records as the album's second single on June 19, 2007. It was written by Carlos "Los Da Mystro" McKinney and fellow singer Terius "The-Dream" Nash.

Chart performance
"Bed" debuted on the U.S. Billboard Hot 100 in the issue week of August 4, 2007 at number 89 and has peaked at number 5. It was number 1 on the Hot R&B/Hip-Hop Songs for five weeks in a row. The single has also debuted on BET's 106 & Park countdown at number 9 on Tuesday July 31, 2007. On Wednesday, August 15, 2007, "Bed" hit number one on its 11th day on the countdown. This song was No. 70 on Rolling Stones list of the 100 Best Songs of 2007. The video for "Bed" was ranked the No. 11 video of 2007 on BET: Notarized.

Live performances
On August 17, 2007, Holiday gave his first televised performance of the song on TRL's MTV Jams. "Bed" was also performed on Showtime at the Apollo along with the single "Suffocate".

Music video
The music video for "Bed" was directed by Jonathan Mannion. The video starts with J. Holiday in his tour bus. Not long after he goes to a motel where he is singing the first verse. There are scenes of the woman that he is singing about though she is not present with him. The first verse also consists of a scene of Holiday singing on a brown wall. Eventually he packs his things and is walking down a deserted road and soon gets to an automobile store and buys a car. He drives to his girlfriend's (video model Jennifer also seen in Omarion's "O" Video) house and she jumps up and hugs him. Night falls and as the song states he puts her to "Bed". The camera then shows him waking up in the morning with his girlfriend still asleep.He picks up his plane tickets and leaves in a taxi, leaving the car he bought at his girlfriend's house.

Remixes
The official remix features American rappers Ja Rule and Trina, and uses the instrumental from R. Kelly's song "Number One", which itself samples Kirko Bangz's "Drank In My Cup" and RUN-DMC's "Walk This Way". The second official remix features American rapper Fabolous. The Third Remix of this song came early 2018 when "Kanye West" had a "Yeezy Season 5" Fashion show in the New York City it was later released on Soundcloud for the masses to hear 17:19 minute remix rework and completely re-done song vocals are done by "The-Dream"

Usage in media
The song appears on the episode of "Stay fierce, Malik" January 23, 2009 on The Game. The song was also used in a dance sequence by Luke James in the 2019 film Little.

Charts

Weekly charts

Year-end charts

Certifications

See also
List of number-one R&B singles of 2007 (U.S.)

References

External links
 J. Holiday Live Rooftop Show
J. Holiday Live @ HOB
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Bed (J. Holiday song)


'Tchoukball'  is an indoor team sport. It was created in the 1970's by Swiss biologist Hermann Brandt. Brandt believed that "The objective of all physical activities is not to make champions, but make a contribution to building a harmonious society". He wanted to create a team sport which did not involve the injuries which he saw as being a problem in other sports.

The sport is usually played on an indoor court that is  by }. At each end, there is a 'frame' (a device similar to a trampoline off which the ball bounces). This frame measures . There is also a semicircular D-shaped area measuring  in radius around the frame which players can not enter. The game is played with two teams of 12 players on each team. Of the twelve players on a team, seven may be on the court at any one time. Each team can score on both ends on the field. In order to score a point, the ball must be thrown by an attacking player, hit the frame and bounce outside the 'D' without being caught by the defending team. Physical contact is not allowed, and defenders may not try to stop the attacking team's passes. Players may take three steps with the ball and can hold the ball for at most three seconds. Teams may not pass the ball more than three times before shooting at the frame.

Tchoukball has become an international sport. It is played in Brazil, Canada, China, the Czech Republic, Great Britain, Hong Kong, India, Italy, Japan, Macau, Singapore, Switzerland, Taiwan, and the United States. It is governed by the Féderation Internationale de Tchoukball (FITB, founded in 1971). Taiwan hosted the 2004 World Championships and won both the women's and junior championships. The Swiss won the men's championship. The 2006, European Championships were held in Switzerland. Great Britain won both the Men's and Under-18's titles. Switzerland won the Ladies event.

Team sports

Tchoukball


Joen Pauli Højgaard Ellefsen (20 April 1936 – 24 August 2012) was a Faroese politician and member of the Union Party. He was Prime Minister of the Faroe Islands from 1981 to 1985.

Pauli Ellefsen was the eldest of eight children born to Sofia (née Højgaard) from Rituvík and Joen Elias Ellefsen from Miðvágur. He was the brother of former Parliament member Svend Aage Ellefsen, and brother-in-law of former parliament member Jóannes Dalsgaard. He was married to Henni Egholm (née Rasmussen). He and his wife lived in Hoyvík, near Tórshavn.

Ellefsen worked as a fisherman from 1954 to 1956. After that, he worked as a telecommunications technician and later he attended a business school in Copenhagen. In 1969, he became a government surveyor. He lived in Denmark while he was studying and a few years after that, but in the early 1970s, he moved back to the Faroes with his family. He and Jógvan Sundstein, who later became Prime Minister of the Faroe Islands, worked together as Chartered Accountants. In 1975 he started his own auditor firm.

Ellefsen was first elected to the Løgting in 1974. From 1974 to 1990 he was the chairman of the Union Party, which advocates a stronger bond between Denmark and the Faroe Islands. From 1977 to 1987 and 1988 to 1990 he was one of the two Faroese members of the Danish Folketing. From 1975 to 1976 and in 1979 he represented the Faroese in the Nordic Council.

Honor
Ellefsen was awarded the Order of the Dannebrog, Knight 1st Class (Ridder af 1. grad) on 7 May 1984.

References

 Løgtingið 150 - Hátíðarrit. Tórshavn 2002, Volume 2, p. 276 (PDF-Download)

1936 births
2012 deaths
People from Miðvágur
Prime Ministers of the Faroe Islands
Union Party (Faroe Islands) politicians
Members of the Folketing
Faroese members of the Folketing
Members of the Løgting
Knights First Class of the Order of the Dannebrog

Pauli Ellefsen


Time-inhomogeneous hidden Bernoulli model (TI-HBM) is an alternative to hidden Markov model (HMM) for automatic speech recognition. Contrary to HMM, the state transition process in TI-HBM is not a Markov-dependent process, rather it is a generalized Bernoulli (an independent) process. This difference leads to elimination of dynamic programming at state-level in TI-HBM decoding process. Thus, the computational complexity of TI-HBM for probability evaluation and state estimation is  (instead of  in the HMM case, where  and  are number of states and observation sequence length respectively). The TI-HBM is able to model acoustic-unit duration (e.g. phone/word duration) by using a built-in parameter named survival probability. The TI-HBM is simpler and faster than HMM in a phoneme recognition task, but its performance is comparable to HMM.

For details, see  or .

References

 Jahanshah Kabudian, M. Mehdi Homayounpour, S. Mohammad Ahadi, "Bernoulli versus Markov: Investigation of state transition regime in switching-state acoustic models," Signal Processing, vol. 89, no. 4, pp. 662–668, April 2009.
  Jahanshah Kabudian, M. Mehdi Homayounpour, S. Mohammad Ahadi, "Time-inhomogeneous hidden Bernoulli model: An alternative to hidden Markov model for automatic speech recognition," Proceedings of the IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP), pp. 4101–4104, Las Vegas, Nevada, USA, March 2008.

Speech recognition
Hidden stochastic models


Eugene Abeshaus (also spelled Evgeny Abezgauz, Евгений Абезгауз in Russian; 1939–2008) was a Jewish artist who worked in Russia (then USSR) and Israel.

Biography
Born in Leningrad to a typical intelligentsia family, Abeshaus was educated as an electrical engineer but soon abandoned this career and enrolled in the Mukhina School for Applied Art. By the time of his graduation from the famous "Mukha" (Fly in Russian), he had already developed a critical stance towards the official Soviet art dominated by the Communist ideology and began exhibiting at semi-underground exhibitions. This was culminated by his taking part in a famous 1975 exhibition at the Nevsky Palace of Culture. Abeshaus was fired from his job and censured by the official press – which however admitted his "artistic taste, a good sense of color and form".

Career
Soon afterwards, Abeshaus set up, together with several Jewish artists, the Alef Group and became its leader. The group's first exhibition in November 1975 was held at Abeshauses' small apartment. According to the Alef Manifesto written by Alec Rappoport, "We are trying to conquer the influence of small-town Jewish art and find sources for our work in deeper, wiser, and more spiritual European culture, and from it build a bridge to today and tomorrow".

In May 1976, some of Abeshaus's works, clandestinely sneaked out of the country, were exhibited at the Berkeley Art Museum to much critical acclaim. Later in the same year, following some political bargain between Leonid Brezhnev and President Jimmy Carter, Abeshaus and his family were finally permitted to leave the USSR for Israel.

Since then Abeshaus lived and worked in Ein Hod, a picturesque artists' village near Haifa founded by Marcel Janco. His works were exhibited at numerous exhibitions, including dozens one-artist shows, in Israel, USA, Europe and, after the collapse of the USSR, in Russia. His ultimate acceptance and recognition there was culminated in a sensational memorial one-artist exhibition staged in 2009 at the famous Russian Museum in St.Petersburg - an exceptional honor for a modern artist.

External links
Artist's homepage
Abeshaus exhibition at the Russian Museum

Jewish artists
Russian Jews
2008 deaths
1939 births

Eugene Abeshaus


Preference falsification is the act of misrepresenting a preference under perceived public pressures. It involves the selection of a publicly expressed preference that differs from the underlying privately held preference (or simply, a public preference at odds with one's private preference). People frequently convey to each other preferences that differ from what they would communicate privately under credible cover of anonymity (such as in opinion surveys to researchers or pollsters). Pollsters can use techniques such as list experiments to uncover preference falsification.

The term preference falsification was coined by Timur Kuran in a 1987 article, "Chameleon voters and public choice." On controversial matters that induce preference falsification, he showed there, widely disliked policies may appear popular. The distribution of public preferences, which Kuran defines as public opinion, may differ greatly from private opinion, which is the distribution of private preferences known only to individuals themselves.

Kuran developed the implications of this observation in a 1995 book, Private Truths, Public Lies: The Social Consequences of Preference Falsification. This book argues that preference falsification is not only ubiquitous but has huge social and political consequences. It provides a theory of how preference falsification shapes collective decisions, sustains social stability, distorts human knowledge, and conceals political possibilities.

Specific form of lying
Preference falsification aims specifically at molding the perceptions others hold about one's motivations. As such, not all forms of lying entail preference falsification. To withhold bad medical news from a terminally ill person is a charitable lie. But it is not preference falsification, because the motivation is not to conceal a wish.

Preference falsification is not synonymous with self-censorship, which is simply the withholding of information. Whereas self-censorship is a passive act, preference falsification is performative. It entails actions meant to project a contrived preference.

Strategic voting occurs when, in the privacy of an election booth, one votes for candidate B because A, one's favorite, cannot win. This entails preference manipulation but not preference falsification, which is a response to social pressures. In a private polling booth, there are no social pressures to accommodate and no social reactions to control.

Private opinion vs. public opinion
The term public opinion is commonly used in two senses. The first is the distribution of people's genuine preferences, often measured through surveys that provide anonymity. The second meaning is the distribution of preferences that people convey in public settings, which is measured through survey techniques that allow the pairing of responses with specific respondents. Kuran distinguishes between the two meanings for analytic clarity, reserving public opinion only for the latter. He uses the term private opinion to describe the distribution of a society's private preferences, known only to individuals themselves.

On socially controversial issues, preference falsification is often pervasive, and ordinarily public opinion differs from private opinion.

Private knowledge vs. public knowledge
Private preferences over a set of options rest on private knowledge, which consists of the understandings that individuals carry in their own minds. A person who privately favors reforming the educational system does so in the belief that, say, schools are failing students, and a new curriculum would serve them better. But this person need not convey to others his sympathy towards a new curriculum. To avoid alienating powerful political groups, she could pretend to consider the prevailing curriculum optimal. In other words, her public knowledge could be a distorted, if not completely fabricated, version of what she really perceives and understands.

Knowledge falsification causes public knowledge to differ from private knowledge.

Three main claims of Kuran's theory
Private Truths, Public Lies identifies three basic social consequences of preference falsification. distortion of social decisions, distortion of private knowledge, and unanticipated social discontinuities.

Distortion of social decisions
Among the social consequences of preference falsification is the distortion of social decisions. In misrepresenting public opinion, it corrupts a society's collective policy choices. One manifestation is collective conservatism, which Kuran defines as the retention of policies that would be rejected in a vote taken by secret ballot and the implicit rejection of alternative policies that, if voted on, would command stable support.

For an illustration, suppose that a vocal minority within this society takes to shaming the supporters of a certain reform. Simply to protect their personal reputations, people privately favoring the reform might start pretending to be satisfied with the status quo. In falsifying their preferences, they would make the perceived share of the reform opponents discourage other reform sympathizers from publicizing their own desires for change. With enough reform sympathizers opting for comfort through preference falsification, a clear majority privately favoring reform could co-exist with an equally clear majority publicly opposing the same reform. In other words, private opinion could support reform even as public opinion opposes it.

A democracy has a built-in mechanism for correcting distortions in public opinion: periodic elections by secret ballot. On issues where preference falsification is rampant, elections allow hidden majorities to make themselves heard and exert influence through the ballot box. The privacy afforded by secret balloting allows voters to cast ballots aligned with their private preferences. As private opinion gets revealed through the ballot box, preference falsifiers may discover, to their delight, that they form a majority. They may infer that they have little to fear from vocalizing honestly what they want. That is the expectation underlying secret balloting.

In practice, however, secret-ballot elections serve their intended corrective function imperfectly. For one thing, on issues that induce rampant preference falsification, elections may offer little choice. All serious contestants will often take the same position, partly to avoid being shamed and partly to position themselves optimally in policy spaces to maximise their appeal to the electorate. For another, in periodic elections citizens of a democracy vote for representatives or political parties that stand for policy packages. They do not vote on individual policies directly. Therefore, the messages that a democratic citizenry conveys through secret balloting are necessarily subject to interpretation. A party opposed to a particular reform may win because of its stands on other issues. Yet, its vote may be interpreted as a rejection of reform.

Nevertheless, periodic secret balloting limits the harms of preference falsification. It keeps public opinion from straying too far from private opinion on matters critical to citizens. By contrast, in nondemocratic political regimes no legal mechanism exists for uncovering hidden sentiments. Therefore, serious distortions of public opinion are correctable only through extra-legal means, such as rioting, a coup, or a revolution.

Distortion of private knowledge
Private preferences may change through learning. We learn from our personal experiences, and we can think for ourselves. Yet, because our cognitive powers are bounded, we can reflect comprehensively on only a small fraction of the issues on which we decide, or are forced to, express a preference. However much we might want to think independently on every issue, our private knowledge unavoidably rests partly on the public knowledge that enters public discourse—the corpus of suppositions, observations, assertions, arguments, theories, and opinions in the public domain. For example, most people's private preferences concerning international trade are based, to one degree or another, on the public communications of others, whether through publications, TV, social media, gatherings of friends, or some other medium.

Preference falsification shapes or reshapes private knowledge by distorting the substance of public discourse. The reason is that, to conceal our private preferences successfully, we must control the impressions we convey. Effective control requires careful management of our body language but also of the knowledge that we convey publicly. In other words, credible preference falsification requires engaging in appropriately tailored knowledge falsification as well. To convince an audience that we favor trade quotas, facts and arguments supportive of quotas must accompany our pro-quota public preference.

Knowledge falsification corrupts and impoverishes the knowledge in the public domain, Kuran argues. It exposes others to facts that knowledge falsifiers know to be false. It reinforces the credibility of falsehoods. And it conceals information that the knowledge falsifier considers true.

Preference falsification is thus a source of avoidable misperceptions, even ignorance, about the range of policy options and about their relative merits. This generally harmful effect of preference falsification works largely through the knowledge falsification that accompanies it. The disadvantages of a particular policy, custom, or regime might have been appreciated widely in the past. However, insofar as public discourse excludes criticism of the publicly fashionable options, the objections will tend to be forgotten. Among the mechanisms producing such collective amnesia is changes is population replacement through births and deaths. New generations are exposed not to the unfiltered knowledge in their elders' heads but, rather, to the reconstructed knowledge that their elders feel safe to communicate. Suppose that an aging generation had disliked a particular institution but refrained from challenging it. Absent experiences that make the young dislike that institution, they will preserve it to avoid social sanctions but also, perhaps mainly, because the impoverishment of public discourse has blinded them to the flaws of the status quo and blunted their capacity to imagine better alternatives. The preference and knowledge falsification of their parents will have left them intellectually handicapped.

Over the long run, then, preference falsification brings intellectual narrowness and ossification. Insofar as it leaves people unequipped to criticize inherited social structures, current preference falsification ceases to be a source of political stability. People support the status quo genuinely, because past preference falsification has removed their inclinations to want something different.

The possibility of such socially induced intellectual incapacitation is highest in contexts where private knowledge is drawn largely from others. It is low, though not nil, on matters where the primary source of private knowledge is personal experience. Two other factors influence the level of ignorance generated by preference falsification. Individuals are more likely to lose touch with alternatives to the status quo if public opinion reaches an equilibrium devoid of dissent than if some dissenters keep publicizing the advantages of change. Likewise, widespread ignorance is more likely in a closed society than in one open to outside influences.

Generating surprise
If public discourse were the only determinant of private knowledge, a public consensus, once in place, would be immutable. In fact, private knowledge has other determinants as well, and changes in them can make a public consensus unravel. But this unraveling need not occur in tandem with growing private opposition to the status quo. For a while, its effect may simply be to accentuate preference falsification (for the underlying logic, see also works by Mark Granovetter, Thomas Schelling, Chien-Chun Yin, and Jared Rubin).  Just as underground stresses can build up for decades without shaking the ground above, so discontents endured silently may make private opinion keep moving against the status quo without altering public opinion. And just as an earthquake can hit suddenly in response to an intrinsically minor tectonic shift, so public opinion may change explosively in response to an event of minor intrinsic significance to personal political incentives. Summarizing Kuran's logic requires consideration of the incentives and disincentives to express a preference likely to draw adverse reactions from others.

In Kuran's basic theory, preference falsification imposes a cost on the falsifier in the form of resentment, anger, and humiliation for compromising his individuality. And this psychological cost grows with the extent of preference falsification. Accordingly, a citizen will find it harder to feign approval of the established policy than if he favors massive reform than if he favors mild reform. In choosing a public preference with respect to the status quo, the individual must also consider the reputational consequences of the preference he conveys to others. If reformists are stigmatized and ostracized, and establishmentarians are rewarded, solely from a reputational standpoint he would find it more advantageous to appear as an establishmentarian. The reputational payoff from any given choice of a public preference depends on the relative shares of society publicly supporting each political option. That is because each camp's rewarding and punishing is done by their members themselves. The camps thus form pressure groups. All else equal, the larger a pressure group, the greater the pressure it exerts on members of society.

Unless the established policy happens to coincide with an individual's private ideal, he thus faces a tradeoff between the internal benefits of expressing himself truthfully and the external advantages of being known as an establishmentarian. To any issue, observes Kuran, individuals can bring different wants, different needs for social approval, and different needs to express themselves truthfully. These possibilities imply that people can differ in their responses to prevailing social pressures. Of two reform-minded individuals, one may resist social pressures and express her preference truthfully while the other opts to accommodate the pressures through preference falsification. A further implication is that individuals can differ in terms of the social incentives necessary to make them abandon one public preference for another. The switchover points define individuals' political thresholds. Political thresholds can vary across individuals for the reasons given above.

We are ready now to explain how, when private opinion and public opinion are far apart, a shock of the right kind can make a critical number of disgruntled individuals reach their thresholds for expressing themselves truthfully to put in motion a public-preference cascade (also known as a public-preference bandwagon, or, when the form of preference is clear from the context, a preference cascade). Until the critical mass is reached, changes in individual dispositions are invisible to outsiders, even to one another. Once it is reached, switches in public preferences impel people with thresholds a bit higher than those of the people within the critical mass add their own voices to the chorus for reform. And support for reform then keeps feeding on itself through growing pro-reform pressure and diminishing pressure favoring the status quo. Each addition to the reformist camp induces further additions until a much larger share of society stands for change. This preference cascade ends when no one is left whose threshold is sufficiently low to be tipped into the reformist camp by one more other individual's prior switch.

This explosive growth in public support for reform amounts to a political revolution. The revolution will not have been anticipated, because preference falsification had concealed political currents flowing under the visible political landscape. Despite the lack of foresight, the revolution will easily be explained with the benefit of hindsight. Its occurrence lowers the personal risk of publicizing preference falsification in the past. Tales of expressive repression expose the vulnerability of the prerevolutionary social order. Though many of these tales will be completely true, others will be exaggerated, and still others will be outright lies. Indeed, the revolution creates incentives for people who were long satisfied genuinely with the status quo to pretend that, at heart, they were always reformists waiting for a prudent time to speak out.

Good hindsight does not imply good foresight, Kuran insists. To understand why we were fooled in the past does not provide immunity to being surprised by future social discontinuities. Wherever preference falsification exists, an unanticipated social break is possible.

Kuran developed his theory of "unanticipated revolution" in an April 1989 article that gave the French Revolution of 1789, the Russian Revolution of February 1917, and the Iranian Revolution of 1978-79 as examples of earth-shattering events that caught the world by surprise. When the Berlin Wall fell in November 1989, and several East European communist regimes fell in quick succession, he interpreted the surprise through an illustrative form of his theory. Both articles predict that revolutionary political surprises are a fact of political life; no amount of modeling and empirical research will provide full predictability as long as public preferences are interdependent and preference falsification exists. In a 1995 article, he emphasized that his unpredictability prediction is falsifiable. He stated as a proposition: "The ubiquity of preference falsification makes more revolutionary surprises inevitable." This proposition "can be debunked," he wrote, "by constructing a theory that predicts future revolutions accurately," illustrating through examples that the predictions would need to specify the timing.

Case studies

Kuran's Private Truths, Public Lies contains three case studies. They involve the trajectory of East European communism, India's caste system, and racial inequality and related policies in the United States. Many other scholars have applied the concept of preference falsification in myriad contexts. Some prominent cases are summarized here, and additional cases are referenced.

Communism's persistence and sudden fall

Persistence of communism
For many decades, the communist regimes of the Eastern Europe, all established during or after World War II as "people's democracies," drew public support from millions of dissatisfied citizens. The reason is only partly that authorities punished dissenters. Citizens seeking to prove their loyalty to communism participated in the vilification of nonconformists, even of dissidents whose political positions they privately admired. This insincerity made it highly imprudent to oppose communism publicly. As such, it contributed to the survival of generally despised communist regimes. Vocal dissenters existed. They included Alexander Solzhenitsyn, Andrei Sakharov, and Václav Havel.  But East European dissidents were far outnumbered by unhappy citizens who opted to appear supportive of the incumbent regime. By and large, dissidents were people with an enormous capacity for enduring social stigma, harassment, and even imprisonment. In terms of the Kuran model, they had uncommonly low thresholds for speaking their minds. Most East Europeans had much higher thresholds. Accordingly, for all the hardships of life under communism, they remained politically submissive for years on end.

Ideological influence
One can privately despise a regime without loss of belief in the principles it stands for. By and large, people who came to disdain communist regimes continued, for decades, to believe in its viability. Most attributed its shortcomings to corrupt leaders, remaining sympathetic to communism itself.

Kuran attributes communism's ideological influence partly to preference falsification on the part of people who felt victimized by it. In concealing their grievances to avoid being punished as an "enemy of the people," victims had to refrain from communicating their observations about communism's failures; they also had to pay lip service to Marxist principles. Their knowledge falsification distorted public discourse enormously, sowing confusion about the shortcomings of communism. Not even outspoken dissidents came out unscathed. Until Mikhail Gorbachev's reforms of the 1980s broke longstanding taboos, most East European dissidents remained committed to some form of socialism.

Well before the fall of communism, during the heyday of Soviet power and apparent invincibility, the dissident Alexander Solzhenitsyn pointed to this phenomenon of intellectual enfeeblement. He said that the Soviet people had become "mental cripples."

The large dissident literature of the communist world provides evidence. Not even courageous social thinkers escaped the damage of intellectual impoverishment. Certain unusually gifted scholars and statesmen recognized that something essential was wrong. From the Khrushchev era (1953–64) onwards, they spearheaded reforms such as Hungarian market socialism and the Yugoslav labor-managed enterprise. But the architects of these reforms failed to recognize the fatal flaws of the system they tried to salvage. Well into the 1980s, most reformers continued to regard central planning as indispensable. They criticized black markets but rarely understood that communism made black markets inevitable. Likewise, the instigators of Hungary's crushed revolution of 1956 and the Prague Spring of 1968 were all wedded to "scientific socialism" as a doctrine of emancipation and shared prosperity.

The Hungarian economist János Kornai struggled in the 1960s to the 1980s to reform the Hungarian economy. His history of reform communism characterizes the reformers of the 1950s and 1960s (including himself) as naive. It was ridiculous, he wrote in 1986, to think that the Soviet command system could be reformed in such a way to ensure efficiency, growth, and equality all at once.

Diverse reformers helped expose communism's unviability. But the biases of socialist public discourse handicapped even them. Their own thinking was warped by the distortions of communist public discourse.

The sudden fall of East European communism
Among the most stunning surprises of the twentieth century is the collapse of several communist regimes in 1989. Practically everyone was stunned by the communist collapse, including scholars, statesmen, futurologists, the CIA, the KGB, and other intelligence organizations, dissidents with great insight into their societies (such as Havel and Solzhenitsyn), and even Gorbachev, whose actions unintentionally triggered this momentous transformation.

A major trigger was the Soviet Union's twin policies of perestroika (restructuring) and glasnost (openness). Perestroika amounted to an acknowledgment, by the Soviet Communist Party that something was seriously wrong, that the Communist system was not about to overtake the West. Glasnost allowed Soviet citizens to participate in debates about the system, to propose changes, to speak the previously unspeakable, to admit that they had been thinking what had been considered unthinkable. Public discourse broadened, heightening disillusionment with communism and intensifying popular discontent. In the process, millions of East European citizens became increasingly willing to support an opposition movement publicly.

Few would step forward, though, so long as the opposition movement remained minuscule. Hence, no one, not even the East Europeans themselves, knew how ready Eastern Europe had become for regime changes.

In retrospect, a turning point was Gorbachev's trip to Berlin on October 7, 1989 for celebrations marking the 40th anniversary of East Germany's communist regime. Crowds fill the streets, chanting "Gorby! Gorby!" The East German police responded with restraint. TV scenes of the demonstrations and the police response signaled, on the one hand, that discontent was very broad and, on the other hand, that the regime was vulnerable. The result was an explosive growth in public opposition, with each demonstration sparking larger demonstrations. The fall of the Berlin Wall came on November 9. Regimes considered unshakeable crumbled, in quick succession, under the weight of open opposition from the streets.

Preference falsification, for decades a source of communism's durability, now made the anti-regime movement in public opinion feed on itself. As public opposition grew, East Europeans relatively satisfied with the status quo jumped on the public-preference cascade to secure a place in the emerging new order. Though the world was caught by surprise, the East European revolutions are now easily understood. In line with Kuran's theory of unanticipated revolutions, abundant information now points to the existence, all along, of massive hidden opposition to the region's parties.

The data that have surfaced include classified opinion surveys found in Communist Party archives. Like rulers of dictatorial regimes throughout history, Party leaders understood that their support partly feigned. For self-preservation, they conducted anonymous opinion surveys whose results were treated as state secrets. The once-classified data show little variation until 1985. They indicate substantial belief in the efficiency of socialist institutions, but also far more doubt than public discourse suggested. After 1985, faith in communism plummeted and the perception that communism is unworkable spread.

A puzzle is why the East European leaders who had access to this information, and who thus knew that disillusionment with communism was growing, did not block the rise in explosive opposition. They probably could have prevented the cascades that were to unfold through massive force early on. Certain communist leaders thought that reforms would ultimately reverse the process. Others did not realize how quickly private discontent could produce self-reinforcing public opposition.

At the very end, fear simply changed sides: party functionaries who had helped foster repression came to fear ending up on the wrong side of history. In retrospect, it appears that their reticence to respond forcefully at the outset enabled public oppositions to grow explosively in country after country, through a domino effect. Each successful revolution lowered the perceived risks of joining the opposition in other countries.

Religious preference falsification
Preference falsification has played a role in the growth and survival of religions. It has contributed also to the shaping of religious institutions and beliefs. Some case studies are summarized here.

India's caste system
For several millennia, Indian society has been divided into ranked occupational units, or castes, whose membership is determined primarily by descent. In practice, the caste system became an integral part of Hinduism in most parts of the Indian subcontinent. Over the ages, this system survived anti-Hindu movements, foreign invasions, colonization, even the challenges of two doctrinally more egalitarian religions, Islam and Christianity. Although discrimination against the lower castes became illegal in post-colonial India, caste remains a powerful force in Indian life. Most marriages take place between members of the same caste.

Persistence of caste system
The extraordinary durability of the caste system has puzzled social scientists, especially because, in most times and places, the system has perpetuated itself with little use of force. A related enigma has been the support given to the system by groups at the foot of the Hindu social hierarchy, namely the Untouchables (Dalits). Because of their deprivations, the Untouchables might be expected to have resisted the caste system en masse.

George Akerlof offers an explanation that hinges on two observations: (1) castes are economically interdependent, and (2) traditional Indian society penalizes people who neglect or refuse to abide by caste codes. For example, if a firm hires an Untouchable to fill a post traditionally reserved for an upper caste, the firm loses customers, and the hired Untouchable endures social punishments. Because of these conditions, no individual can break away from the caste system unilaterally. To succeed, he must break away as part of a coalition. But free riding blocks the formation of viable coalitions. Because the rule breaker would suffer negative consequences immediately and without any guarantee of success, no firm and no Untouchable initiates a break.

In Private Truths, Public Lies, Kuran observes that Indians were penalised not just for actions against the caste system but also for expressions of opposition. The caste system discouraged inquiries into its rationale. It also discouraged open criticism of caste rules. By and large, the reservations of Indians remained suppressed. Preference falsification with respect to the system was common, as was knowledge falsification. Based on these findings and focusing on processes that shape public opinion and public knowledge, Kuran extends Akerlof's theory.

Reticence to publicize preferences and knowledge honestly kept Indians in the dark, Kuran argues, about opportunities for forming anti-caste coalitions. It made them perceive the caste system as inescapable, even in contexts where, collectively, they had the power to change, even overthrow, the system. Hence, before the 1800s, negotiations for a more egalitarian social contract did not get off the ground. Reform-minded Indians could not find each other, let alone initiate discussions leading to reforms.

Caste ideology
The caste system was legitimized through a tenet of Hinduism, the doctrine of karma. According to this doctrine, an individual's behavior in one life affects his social status in his later lives. If a person accepts his caste of birth and fulfils the tasks accepted of him without making a fuss, he gets reincarnated into a higher caste. If instead he neglects the duties of the caste into which he was born or challenges the caste system, he gets demoted in his next life. Accordingly, the karma doctrine treats prevailing status differences as the fair and merited consequences of past conduct.

Many ethnographies find that, to close friends, low-ranked Indians will confess doubts about karma, if not outright lack of belief in it. But preference and knowledge falsification by Indians, even by substantial numbers, does not imply that the doctrine is merely a façade. Over countless generations, many Indians internalized the doctrine of karma. Belief in social mobility through reincarnation has been common; so has belief in ritual impurity, which Hinduism treats as both a source and a manifestation of social inferiority.

These concepts emerged so long ago that their origins are poorly understood. It is clear, though, that, once the caste system got established, the highest-status castes, the brahmins, had incentives to perpetuate the caste system by punishing Indians who misbehaved or expressed disapproval. As Kuran explains, preference and knowledge falsification made some Indians obey the system for fear of reprisals and others out of conviction. In either case, public discourse facilitated the acceptance of karma-based status differences. Most Indians remained ignorant of concepts critical to treating their conditions as unacceptable. Insofar as Indians genuinely believed in caste ideology, the caste system strengthened.

In the 19th century, the caste system came to be questioned widely in public. The key trigger was that growing numbers of Indians became acquainted with egalitarian European movements, such as democratisation, liberalism, and socialism. The ensuing Indian reform movement led, in the second half of the 20th century, to a system of caste-based education and job quotas meant to assist the most disadvantaged groups within Indian society, including the Untouchables.

Shii Islam's taqiyya doctrine
After Islam's Sunni-Shii schism in 661 CE, Sunni leaders took to persecuting Shiis living in their domains. Their campaign to extinguish Shiism included requiring suspected Shiis to insult the founders of Shiism. Refusal to comply could result in imprisonment, torture, even death. In response, Shii leaders adopted a doctrine that allowed individual Shiis to conceal their Shii beliefs in the face of danger, provided they met two criteria. First, the preference falsifiers would stay devoted, in their hearts, to Shii tenets; and second, they would intend, as soon as the danger passed, to return to practicing Shiism openly. This form of religious preference falsification was known as taqiyya.

Shii leaders gave taqiyya religious legitimacy through Quran verses that speak of God's omniscience; God saw, on the one hand, people's private and public preferences, and, on the other hand, the conditions making religious preference falsification a matter of survival. He would sympathize with taqiyya exercised for legitimate reasons by people who, at least privately, retained the correct faith.

Gradually, the taqiyya doctrine turned into a justification for Shii political passivity. Stretching the meaning of this doctrine, many Shiis living under an oppressive regime used it to rationalize inaction, even apathy. In the 20th century, growing numbers of Shii leaders took to telling their followers that taqiyya had been a key source of Shii political and economic weakness. The mastermind of Iran's Revolution of 1979, Ayatollah Ruhollah Khomeini, opened his campaign to topple the Pahlavi Monarchy by proclaiming: "The time for taqiyya is over. Now is the time for us to stand up and proclaim the things we believe in." The success of Khomeini's campaign involved millions of Iranians joining street protests against the Pahlavi regime, at the risk of being caught, if not killed on the spot, by the regime's widely feared security forces.

Once it consolidated power, Iran's Islamic Republic founded by Khomeini's team did not institute religious freedoms. In forcing Iranians to live according to its specific interpretation of Shiism, it effectively induced a new form of taqiyya. Having the regime's morality police enforce a conservative dress code for women (hijab) resulted in rampant religious preference falsification of a new kind. Against their will, millions of Iranian women started covering their hair and abiding by the regime's modesty standards in myriad ways, simply to avoid punishment. Evidence lies in the commonness of mini headscarves that cover just enough hair to pass as veiled. These headscarves are known pejoratively as "bad hijab" or "slutty hijab." They represent attempts by Iranian women to minimize the extent of their religious preference falsification.

Crypto-Protestantism in France, 1685-1787
Between the Edict of Nantes (1598) and the Edict of Fontainebleau (1685), Protestantism enjoyed toleration in France. The latter edict inaugurated a period when Protestantism was officially proscribed, except in Alsace and Lorraine. Many French Protestants emigrated to Switzerland, Great Britain, British North America, Prussia, and other predominantly Protestant territories. At least officially, the Protestants who stayed behind converted to Roman Catholicism. Of these converts, some practiced Catholicism in public even as they performed Protestant rites privately. Such crypto-Protestantism is a form of religious preference falsification.

During the Revocation period, appearing as a Catholic was a matter of survival. But the required public performances varied across groups and by location, as did crypto-Protestant practices. For example, the Jaucourt family, a noble crypto-Protestant house, discreetly fulfilled its religious commitments at the Protestant chapels of Scandinavian embassies. Catholic authorities, both state officials and Catholic clergy, looked the other way.

For most of the crypto-Protestant population, however, the medium for performing Protestant rites was Désert Church. This was a clandestine network of congregations that operated throughout France with the help of lay crypto-Protestants and Reformed Protestant clerics. Initially, these clerics were domestically trained. Eventually, they were all foreign-trained.

Public performance of Catholic rites gave crypto-Protestants access to civil status deeds as well as official registrations of births, baptisms, and marriages. These incentives for religious preference falsification were not trivial. For example, legal marriage gave offspring legitimacy and inheritance rights. Désert marriages had no legal standing.

French Protestants regained the right to legal marriage as Protestants 102 years after the Edict of Fontainebleau, with the Edict of Tolerance (1787).

Covert Judaism and Islam during the Portuguese Inquisition
In 1496, King Manuel I of Portugal decreed the expulsion of Jews and free Moors from his kingdom and dominions, unless they converted to Christianity. Four decades later, during the reign of John III, Portugal's Holy Office of the Inquisition was established. It began to persecute people accused of crypto-Judaism, crypto-Islam, or some other form of religious preference falsification.

The Portuguese Inquisition functioned as a persecutory organization against covert practices of other religions, but also against heresies and deviations from sexual mores considered un-Christian, such as bigamy and sodomy. The Inquisition pursued these missions until at least the 1770s, when the government of the Marquis of Pombal repurposed this institution.  The Portuguese Inquisition was terminated in 1821.

Iberian-Jewish (Sephardic) converts to Catholicism and their descendants were all known as "New Christians." The Islamic converts and their descendants were known collectively as Mouriscos.  On pain of social rejection and inquisitorial persecution, they were required to display, convincingly enough, their adherence to Roman Catholicism.

Blood purity statutes regulated access to Portugal's public posts and honorific distinctions (also called limpeza de sangue), denying a broad range of privileges to New Christians on account of their heredity. But they could move upward by a combination of marrying "Old Christians" and having records of their roots altered. Diverse entities, including the Inquisition, were used to help New Christians whitewash their heritage through "blood purity" certificates, invariably in return for fees. This whitewashing process involved knowledge falsification by both sides.

The credibility of blood purity certificates depended on the issuing entity's place in Portugal's hierarchy. Accordingly, New Christians could keep rising in social status through blood purity certificates of increasing rigor. More rigorous certificates could be obtained from higher-level investigations also to confront rumors of impure ancestry. Many Portuguese families with New Christian roots progressed upwards in social status by creating availability cascades of positive blood purity certifications. Such families bolstered the availability of information pointing to blood purity also by placing relatives in the Roman Catholic clergy. These placements served themselves as certifications, for the clergy was closed to Christians of "impure" ancestry (namely Jewish, Moorish, and Sub-Saharan African).

Gender norms
According to a 2020 study, by Leonardo Bursztyn, Alessandra González, and David Yanagizawa-Drott, the vast majority of young married men in Saudi Arabia express private beliefs in support of women working outside the home. At the same time, they substantially underestimate the degree to which other similar men support it. Once they become informed about the widespread nature of the support, they increasingly help their wives obtain jobs.

Ethnic conflict
In "Ethnic norms and their transformation through reputational cascades," Kuran applies the concept of preference falsification to ethnic conflict. The article focuses on ethnification, the process whereby ethnic origins, ethnic symbols, and ethnic ties gain salience and practical significance.

Ethnicity often serves as a source of identity without preventing cooperation, exchanges, socializing and intermarriage across ethnic boundaries. In such contexts, social forces may preserve that condition indefinitely. People who harbor ill-will toward other ethnic groups will keep their hatreds in check to avoid being punished for divisiveness. But if political and economic shocks weaken those forces, a process of ethnification may get under way. Specifically, people may start highlighting their ethnic particularities and discriminating against ethnic others. The emerging social pressures will then generate further ethnification through a self-reinforcing process, possibly leading to spiraling ethnic conflict.

An implication of Kuran's analysis is that culturally, politically, economically, and demographically similar countries may exhibit very different levels of ethnic activity. Another is that ethnically based hatreds may constitute by-products of ethnification rather than their mainspring.

Yugoslav Civil War
Kuran uses the above argument to illuminate how the former Yugoslavia, once touted as the model of a civilized multiethnic nation, became ethnically segregated over a short period and dissolved into ethnically based enclaves at war with one another. Preference falsification increased the intensity of the Yugoslav Civil War, he suggests; also, it accelerated Yugoslavia's break-up into ethnically based independent republics.

Further reading

 Chapkovski, Philipp; Max Schaub (2022). "Solid support or secret dissent? A list experiment on preference falsification during the Russian war against Ukraine." Research & Politics 9(2): 1-6.
 Cook, Philip; Heilmann, Conrad (2013). "Two types of self-censorship: Public and private." Political Studies. 61(1): 178–196.
 Crabtree, Charles; Kern, Holger L.; Siegel, David A. (2020). "Cults of personality, preference falsification, and the dictator's dilemma." Journal of Theoretical Politics, 32(3): 409-434.
 Duffy, John; Lafky, Jonathan (2021). "Social conformity under evolving private preferences." Games and Economic Behavior. 128: 104–124.
 Frank, Robert (1996). "The political economy of preference falsification." Journal of Economic Literature. 34(1):115–123.
 Jiang, Junyan; Yang, Dali L. (2016). "Lying or believing? Measuring preference falsification from a political purge in China." Comparative Political Studies. 49 (5): 600–634.
 Kalinin, K. (2018). "Linking preference falsification and election fraud in electoral autocracies: The case of Russia." Political Studies, 66(1), 81-99.
 Loury, Glenn C. (1994). "Self-censorship in public discourse: A theory of 'political correctness' and related phenomena." Rationality and Society. 6 (4): 428–461.

See also
Abilene paradox
Cognitive bias
Crypto-fascism
Collapse of communism
False consensus
Honne and tatemae
Iranian Revolution
Knowledge falsification
Lying
Manufacturing Consent
Overton window
Pluralistic ignorance
Revolutions
Russian Revolution
Secret ballot
Shy Tory factor
Signalling theory
Social desirability bias
Social proof
Spiral of silence

References

Bibliography

External links
 ; Eric Weinstein interviews Timur Kuran

Motivational theories
Political theories
Deception

Preference falsification


The prime minister of Yugoslavia () was the head of government of the Yugoslav state, from the creation of the Kingdom of Serbs, Croats and Slovenes in 1918 until the breakup of the Socialist Federal Republic of Yugoslavia in 1992.

History

Kingdom of Yugoslavia

The Kingdom of Serbs, Croats and Slovenes was created by the unification of the Kingdom of Serbia (Montenegro had united with Serbia five days previously, while the regions of Kosovo and Metohija, Baranya, Syrmia, Banat, Bačka and Vardar Macedonia were parts of Serbia prior to the unification) and the provisional State of Slovenes, Croats and Serbs (itself formed from territories of the former Austria-Hungary) on 1 December 1918.

Until 6 January 1929, the Kingdom of Serbs, Croats and Slovenes was a parliamentary monarchy. On that day, King Alexander I abolished the Vidovdan Constitution (adopted in 1921), prorogued the National Assembly and introduced a personal dictatorship (so-called 6 January Dictatorship). He renamed the country Kingdom of Yugoslavia on 3 October 1929, and although introduced the 1931 Constitution, he continued to rule as a de facto absolute monarch until his assassination on 9 October 1934, during a state visit to France. After his assassination, parliamentary monarchy was put back in place.

The Kingdom of Yugoslavia was defeated and occupied on 17 April 1941 after the German invasion. The monarchy was formally abolished and the republic proclaimed on 29 November 1945.

SFR Yugoslavia

After the German invasion and fragmentation of the Kingdom of Yugoslavia, the Partisan resistance in occupied Yugoslavia formed a deliberative council, the Anti-Fascist Council of National Liberation of Yugoslavia (AVNOJ) in 1942. On 29 November 1943 the AVNOJ proclaimed the Democratic Federal Yugoslavia, and appointed the National Committee for the Liberation of Yugoslavia (NKOJ), led by Prime Minister Josip Broz Tito, as its government. Josip Broz Tito was quickly recognized by the Allies at the Tehran Conference, and the royalist government-in-exile in London was pressured into agreeing on a merge with the NKOJ. In order to facilitate this, Ivan Šubašić was appointed by the King to head the London government.

For a period, Yugoslavia had two recognized prime ministers and governments (which both agreed to formally merge as soon as possible): Josip Broz Tito leading the NKOJ in occupied Yugoslavia, and Ivan Šubašić leading the King's government-in-exile in London. With the Tito-Šubašić Agreement in 1944, the two prime ministers agreed that the new joint government would be led by Tito. After the liberation of Yugoslavia's capital Belgrade in October 1944, the joint government was officially formed on 2 November 1944, with Josip Broz Tito as the prime minister.

After the war, elections were held ending in an overwhelming victory for Tito's People's Front. The new parliament deposed King Peter II on 29 November 1945, and declared a Federal People's Republic of Yugoslavia (in 1963, the state was renamed Socialist Federal Republic of Yugoslavia). The government was first headed by a prime minister up to 14 January 1953, when major decentralization reforms reorganized the government into the Federal Executive Council chaired by a President, who was still usually called "Prime Minister" in non-Yugoslav sources. Josip Broz Tito held the post from 1944 to 1963; from 1953 onward, he was also President of the Republic.

Five out of nine heads of government of Yugoslavia in this period were of Croatian ethnicity. Three were from Croatia itself (Josip Broz Tito, Mika Špiljak, and Milka Planinc), while two were Bosnian Croats (Branko Mikulić and Ante Marković). Ante Marković however, though a Croat from Bosnia and Herzegovina by birth, was a politician of Croatia like Špiljak and Planinc, serving (at different times) as both prime minister and president of the presidency of that federal unit.

List

Timeline

See also
 Deputy Prime Minister of Yugoslavia
 List of heads of state of Yugoslavia
 Chairman of the Council of Ministers of Bosnia and Herzegovina
 Prime Minister of Croatia
 Prime Minister of Serbia and Montenegro
 Prime Minister of Montenegro
 Prime Minister of North Macedonia
 Prime Minister of Serbia
 Prime Minister of Slovenia

References

Government of Yugoslavia
Yugoslavia

Prime ministers
1918 establishments in Yugoslavia
1992 disestablishments in Yugoslavia

Prime Minister of Yugoslavia