The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
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, diabetes mellitus type 1, Henoch–Schönlein purpura, systemic lupus erythematosus, Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, and multiple sclerosis. Autoimmune diseases are very often treated with steroids.
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
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.
Cytotoxic T-lymphocyte associated protein 4, (CTLA-4) 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. It is encoded by the gene CTLA4 in humans.
Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.
Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear.
B-lymphocyte antigen CD20 or CD20 is B lymphocyte cell-surface molecule.
The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kbp gene on chromosome 21q22.3 that encodes 545 amino acids. AIRE is a transcription factor expressed in the medulla of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.
CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases.
In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word adiuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."
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 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.
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a cytoplasmatic protein encoded by gene PTPN22 and a member of PEST family of protein tyrosine phosphatases. This protein is also called "PEST-domain Enriched Phosphatase" ("PEP") or "Lymphoid phosphatase" ("LYP"). The name LYP is used strictly for the human protein encoded by PTPN22, but the name PEP is used only for its mouse homolog. However, both proteins have similar biological functions and show 70% identity in amino acid sequence. PTPN22 functions as a negative regulator of T cell receptor (TCR) signaling, which maintains homeostasis of T cell compartment.
Tyrosine-protein kinase BLK, also known as B lymphocyte kinase, is a non-receptor tyrosine kinase that in humans is encoded by the BLK gene. It is of the Src family of tyrosine kinases.
Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.
CD79b molecule, immunoglobulin-associated beta, also known as CD79B, is a human gene.
Protective autoimmunity is a condition in which cells of the adaptive immune system contribute to maintenance of the functional integrity of a tissue, or facilitate its repair following an insult. The term ‘protective autoimmunity’ was coined by Prof. Michal Schwartz of the Weizmann Institute of Science (Israel), whose pioneering studies were the first to demonstrate that autoimmune T lymphocytes can have a beneficial role in repair, following an injury to the central nervous system (CNS). Most of the studies on the phenomenon of protective autoimmunity were conducted in experimental settings of various CNS pathologies and thus reside within the scientific discipline of neuroimmunology.
An autoimmune disease is a condition that results from an anomalous response of the adaptive 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.
