Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Immune system wikipedia , lookup
Psychoneuroimmunology wikipedia , lookup
Lymphopoiesis wikipedia , lookup
Immunosuppressive drug wikipedia , lookup
Molecular mimicry wikipedia , lookup
Polyclonal B cell response wikipedia , lookup
Adaptive immune system wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Natural killer cell Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. They kill cells by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis (programmed cell death). NK cells are defined as large granular lymphocytes (LGL) and constitute the third kind of cells differentiated from the common lymphoid progenitor generating B and T lymphocytes. They were named "natural killers" because of the initial notion that they do not require activation in order to kill cells that are missing "self" markers of major histocompatibility complex (MHC) class I. They are distinct from Natural Killer T cells. [Note: Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK) cells] Mechanism 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 would only release the virions, whereas apoptosis leads to destruction of the virus inside. NK cells are activated in response to interferons or macrophage-derived cytokines. They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection. Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection. In order 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. Most of these receptors are not unique to NK cells and can be present in some T cell subsets as well. These inhibitory receptors recognize MHC class I alleles, which could explain why NK cells kill cells possessing low levels of MHC class I molecules. This inhibition is crucial to the role played by NK cells. MHC class I molecules consist of the main mechanism by which cells display viral or 1 tumor antigens to cytotoxic T-cells. A common evolutionary adaption to this seen in both intracellular microbes and tumours is a chronic down-regulation of these MHC I molecules, rendering the cell impervious to T-cell mediated immunity. It is believed that NK cells, in turn, evolved as an evolutionary response to this adaption, as the loss of the MHC would deprive these cells of the inhibitory effect of MHC and render these cells vulnerable to NK cell mediated apoptosis. T cell T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells (NK cells) by the presence of a special receptor on their cell surface called T cell receptors (TCR). The abbreviation T, in T cell, stands for thymus, since this is the principal organ responsible for the T cell's maturation. Several different subsets of T cells have been discovered, each with a distinct function. Types Helper T helper cell (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages, among other functions. These cells are also known as CD4 + T cells because they express the CD4 protein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules that are expressed on the surface of Antigen Presenting Cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. 2 Cytotoxic Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body. Memory Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. Memory T cells comprise two subtypes: central memory T cells (T CM cells) and effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+. Regulatory Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Natural killer (see before) γδ A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains. However, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain. B cell B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by T cells). The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells (APCs) and eventually develop into memory B cells after activation by antigen interaction. B cells are an essential component of the adaptive immune system. The abbreviation "B", in B cell, comes from the bursa of Fabricius in birds, where they mature. In mammals, immature B cells are formed in the bone marrow, which is used as a backronym for the cells' name. Immune Tolerance Like their fellow lymphocytes, the T cells, immature B cells are tested for auto-reactivity by the immune system before leaving the bone marrow. In the bone marrow (the central lymphoid organ), central tolerance is produced. The immature B cells whose B cell Receptors (BCRs) bind 3 too strongly to self antigens will not be allowed to mature. If B cells are found to be highly reactive to self, three mechanisms can occur. Clonal deletion: the removal, usually by apoptosis, of B cells of a particular self antigen specificity. Receptor editing: the BCRs of self reactive B cells are given an opportunity to rearrange their conformation. This process occurs via the continued expression of the Recombination activating gene (RAG). Through the help of RAG, receptor editing involves light chain gene rearrangement of the B cell receptor. If receptor editing fails to produce a BCR that is less autoreactive, apoptosis will occur. Note that defects in the RAG-1 and RAG-2 genes are implicated in Severe Combined Immunodeficiency (SCID). The inability to recombine and generate new receptors lead to failure of maturity for both B cells and T cells. Anergy: B cells enter a state of permanent unresponsiveness when they bind with weakly cross-linking self antigens that are small and soluble. T-cell activation: 4 Mechanism of action of B cell 5