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T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
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. They 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 cells,stressed cells,tumor cells,and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces,but NK cells can 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.
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.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer,improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
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.
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.
In immunology,an immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T cell,B cell,or natural killer cell. The interface was originally named after the neuronal synapse,with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation,which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research.
In immunology,a naive T cell (Th0 cell) is a T cell that has differentiated in the thymus,and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naive forms of helper T cells (CD4+) and cytotoxic T cells (CD8+). Any naive T cell is considered immature and,unlike activated or memory T cells,has not encountered its cognate antigen within the periphery. After this encounter,the naive T cell is considered a mature T cell.
Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer;the most well known application is cancer immunotherapy,which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.
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.
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.
Programmed cell death protein 1(PD-1),. PD-1 is a protein encoded in humans by the PDCD1 gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases,but it can also prevent the immune system from killing cancer cells.
Lymphocyte-activation gene 3,also known as LAG-3,is a protein which in humans is encoded by the LAG3 gene. LAG3,which was discovered in 1990 and was designated CD223 after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000,is a cell surface molecule with diverse biological effects on T cell function but overall has an immune inhibitory effect. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.
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 IFNγproducing 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.
Tumor necrosis factor receptor superfamily member 18 (TNFRSF18),also known as glucocorticoid-induced TNFR-related protein (GITR) or CD357. GITR is encoded and tnfrsf18 gene at chromosome 4 in mice. GITR is type I transmembrane protein and is described in 4 different isoforms. GITR human orthologue,also called activation-inducible TNFR family receptor (AITR),is encoded by the TNFRSF18 gene at chromosome 1.
T helper 3 cells (Th3) are a subset of T lymphocytes with immunoregulary and immunosuppressive functions,that can be induced by administration of foreign oral antigen. Th3 cells act mainly through the secretion of anti-inflammatory cytokine transforming growth factor beta (TGF-β). Th3 have been described both in mice and human as CD4+FOXP3− regulatory T cells. Th3 cells were first described in research focusing on oral tolerance in the experimental autoimmune encephalitis (EAE) mouse model and later described as CD4+CD25−FOXP3−LAP+ cells,that can be induced in the gut by oral antigen through T cell receptor (TCR) signalling.
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy,T cells are extracted from the patient,genetically modified and cultured in vitro and returned to the same patient. Comparatively,allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
Short Course Immune Induction Therapy or SCIIT,is a therapeutic strategy employing rapid,specific,short term-modulation of the immune system using a therapeutic agent to induce T-cell non-responsiveness,also known as operational tolerance. As an alternative strategy to immunosuppression and antigen-specific tolerance inducing therapies,the primary goal of SCIIT is to re-establish or induce peripheral immune tolerance in the context of autoimmune disease and transplant rejection through the use of biological agents. In recent years,SCIIT has received increasing attention in clinical and research settings as an alternative to immunosuppressive drugs currently used in the clinic,drugs which put the patients at risk of developing infection,cancer,and cardiovascular disease.
Cytokine-induced killer cells (CIK) cells are a group of immune effector cells featuring a mixed T- and natural killer (NK) cell-like phenotype. They are generated by ex vivo incubation of human peripheral blood mononuclear cells (PBMC) or cord blood mononuclear cells with interferon-gamma (IFN-γ),anti-CD3 antibody,recombinant human interleukin (IL)-1 and recombinant human interleukin (IL)-2.
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance,which prevents the immune system from attacking cells indiscriminately. However,some cancers can protect themselves from attack by stimulating immune checkpoint targets.
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