In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP) sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis.
FOXP3, also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues.
CTLA-4 or CTLA4, also known as CD152, is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells.
In immunology, central tolerance is the process of eliminating any developing T or B lymphocytes that are autoreactive, i.e. reactive to the body itself. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides. Lymphocyte maturation occurs in primary lymphoid organs such as the bone marrow and the thymus. In mammals, B cells mature in the bone marrow and T cells mature in the thymus.
Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is a rare autoimmune disease. It is one of the autoimmune polyendocrine syndromes. Most often, IPEX presents with autoimmune enteropathy, dermatitis (eczema), and autoimmune endocrinopathy, but other presentations exist.
Molecular mimicry is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, a single antibody or TCR can be activated by just a few crucial residues which stresses the importance of structural homology in the theory of molecular mimicry. Upon the activation of B or T cells, it is believed that these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is a phenomenon that has been just recently discovered as one of several ways in which autoimmunity can be evoked. A molecular mimicking event is, however, more than an epiphenomenon despite its low statistical probability of occurring and these events have serious implications in the onset of many human autoimmune disorders.
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. The protein is also known as IL-23p19. It is one of the two subunits of the cytokine Interleukin-23.
Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.
Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family, composed of STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6. STAT proteins are key activators of gene transcription which bind to DNA in response to cytokine gradient. STAT proteins are a common part of Janus kinase (JAK)- signalling pathways, activated by cytokines.STAT4 is required for the development of Th1 cells from naive CD4+ T cells and IFN-γ production in response to IL-12. There are two known STAT4 transcripts, STAT4α and STAT4β, differing in the levels of interferon-gamma production downstream.
T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been termed as Treg17 cells.
T-box transcription factor TBX21, also called T-bet is a protein that in humans is encoded by the TBX21 gene. Though being for long thought of only as a master regulator of type 1 immune response, T-bet has recently been shown to be implicated in development of various immune cell subsets and maintenance of mucosal homeostasis.
Interleukin 35 (IL-35) is a recently discovered anti-inflammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.
Hepatitis A virus cellular receptor 2 (HAVCR2), also known as T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), is a protein that in humans is encoded by the HAVCR2 (TIM-3)gene. HAVCR2 was first described in 2002 as a cell surface molecule expressed on IFNγ producing CD4+ Th1 and CD8+ Tc1 cells. Later, the expression was detected in Th17 cells, regulatory T-cells, and innate immune cells. HAVCR2 receptor is a regulator of the immune response.
An autoimmune disease is a condition that results from an anomalous response of the immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.
Regulatory B cells (Bregs or Breg cells) represent a small population of B cells that participates in immunomodulation and in the suppression of immune responses. The population of Bregs can be further separated into different human or murine subsets such as B10 cells, marginal zone B cells, Br1 cells, GrB+B cells, CD9+ B cells, and even some plasmablasts or plasma cells. Bregs regulate the immune system by different mechanisms. One of the main mechanisms is the production of anti-inflammatory cytokines such as interleukin 10 (IL-10), IL-35, or transforming growth factor beta (TGF-β). Another known mechanism is the production of cytotoxic Granzyme B. Bregs also express various inhibitory surface markers such as programmed death-ligand 1 (PD-L1), CD39, CD73, and aryl hydrocarbon receptor. The regulatory effects of Bregs were described in various models of inflammation, autoimmune diseases, transplantation reactions, and in anti-tumor immunity.
Tolerogenic therapy aims to induce immune tolerance where there is pathological or undesirable activation of the normal immune response. This can occur, for example, when an allogeneic transplantation patient develops an immune reaction to donor antigens, or when the body responds inappropriately to self antigens implicated in autoimmune diseases. It must provide absence of specific antibodies for exactly that antigenes.
Howard L. Weiner is an American neurologist, neuroscientist and immunologist who is also a writer and filmmaker. He performs clinical and basic research focused on multiple sclerosis (MS) and other neurologic diseases such as Alzheimer's disease and Lou Gehrig's disease (ALS). His work also focuses on autoimmune diseases such as diabetes. Weiner is the Robert L. Kroc Professor of Neurology at Harvard Medical School, director of the Brigham MS Center at the Brigham and Women's Hospital and co-director of the Ann Romney Center for Neurologic Diseases established in 2014, at the Brigham and Women's Hospital in Boston, Massachusetts.
Type 1 regulatory cells or Tr1 (TR1) cells are a class of regulatory T cells participating in peripheral immunity as a subsets of CD4+ T cells. Tr1 cells regulate tolerance towards antigens of any origin. Tr1 cells are self or non-self antigen specific and their key role is to induce and maintain peripheral tolerance and suppress tissue inflammation in autoimmunity and graft vs. host disease.
Th17 pathogenic refers to a distinct phenotype of Th17 cells which is associated with immunopathology. The development of the pathogenic phenotype can be shaped by various environmental stimuli and genetic factors. In humans, Th17 pathogenic cells are associated with diseases like multiple sclerosis (MS) or rheumatoid arthritis (RA) and in mice with experimental autoimmune encephalomyelitis (EAE). Th17 pathogenic cells are known to display pro-inflammatory features like expressing transcription factor T-bet and secreting cytokine IFNγ, resembling Th1-like phenotype. Th17 cells are a very heterogenous subset and can switch to display all T helper-like phenotype markers including those typical for Th2, Treg and Tfh.
