Key Compontents of Adaptive System Response

KEY COMPONTENT S OF ADAP T IVE SYSTEM RESPONSE Major histocompatibility complex (MHC) • • • • • • • Encode genes for glycoprotein molecules capture foreign antigen within the cell and display fragments of these foreign antigens on the cell surface for interaction with T lymphocytes MHC molecule contains a cleft where the fragment of foreign antigen is held and taken to the cell surface T cells then recognise that specific MHC molecule-antigen combination MHC Class I MHC Class I molecules combine with viral particles that are produced in the cell cytoplasm and display the viral antigens on the cell surface Class I molecules are recognised by CD8 T cells • • MHC Class II MHC Class II molecules combine with antigen fragments that are contained within vesicles within cells including the antigen bound by antibody after macrophages have engulfed it Class II molecules are recognised by CD4 T cells T cells must express both the antigen receptor + co-receptor that recognises MHC I (CD8) or MHC II (CD4) Once stimulated by combination with the target antigen, T cells release a large array of cytokines to allow them to fulfil their effector function Lymphocyte receptor repertoire • • • Each naïve lymphocyte bears receptors with just one single specificity During development in the bone marrow (B cells) and in the thymus (T cells), millions of different genetic recombinations occur in the genes that encode for lymphocyte receptors → lymphocyte clone is present to recognise almost every conceivable antigen Self-tolerance: lymphocytes that are potentially self-reacting undergo clonal deletion during development Natural killer cells • • • • Lymphocytes that are a part of innate system → do not display antigen-specific receptors Large granular lymphocytes Role is to destroy infected and malignant cells Recognize their targets: o Killer activating receptors and killer-inhibitory receptors ▪ Killer-activating receptors recognize a number of different molecules present on the surface of all nucleated cells ▪ Killer inhibitory receptors recognize MHC class I molecules o Fc receptors that bind IgG ▪ Antibody-dependent cellular cytotoxicity Antibodies • • • • • • • Consist of a constant region of which there are a limited number of forms → function is to dispose of the antigen once bound Variable region which combines with antigen and is antigen-specific Block pathogen entry into cell by combining with them → neutralisation Constant region of the antibody molecule is recognised by phagocytes, so will destroy the antigen when it is attached to the antibody → opsonisation Antibodies bound to antigen form a receptor for the first component of complement Once C1 is activated, a cascade of enzymic reactions occurs, known as the complement cascade, with the complement proteins attacking the pathogen’s cell wall and destroying it Adaptive immunity involving B cells and antibodies is known as humoral immunity Clonal expansion in adaptive immunity • • • • • When a naïve circulating lymphocyte is presented with its specific antigen by an APC, it stops circulating, becomes larger, and within a short space of time turns into a lymphoblast Lymphoblast will begin a phase of rapid division and may divide into 1000 identical daughter cells Differentiated B cells are plasma cells and secrete a large amount of antibody Differentiated T cells are effector cells, which either direct other cells, or destroy infected cells Activated lymphocytes also express cell surface adhesion molecules which allow them to migrate into or remain in the site of infection Second signals • • Combination of the lymphocyte receptor with its antigen is not enough on its own to stimulate the lymphocyte response Second signal in the form of a co-stimulatory molecule is needed • • Ag-presenting cell provides the second signal for the T cell T cell provides the second signal for the B cell Immunological memory • Most of the effector lymphocytes undergo apoptosis after the infection has subsided, but some remain as memory cells → allow the immune system to recognise and fight a re-infection more quickly Cell-mediated immunity • • • Viruses, some bacteria, other pathogens are located within host cells → out of reach of antibodies Antigens derived from the replicating virus within a cell are displayed on the cell surface Effector T cells (CD8 cells) recognise these antigens and destroy the cell TH1 and TH2 cells • • • • • • • Some pathogens when engulfed by macrophages are incorporated into lysosomes inside macrophage → contains enzymes that destroy the pathogen Other organisms are contained within (and replicate in) vesicles that do not fuse with the lysosome membrane, and therefore survive e.g. Mycobacterium tuberculosis TH1 subset of the CD4 lymphocytes are able to induce fusion of the lysosome with the vesicle containing the bacteria by activating macrophages, and also activate other bactericidal mechanisms TH1 cells also release chemoattractants for recruitment of further macrophages TH2 subset of CD4 lymphocytes act to stimulate B cells to produce immunoglobulin Immunoglobulin (antibody) can destroy extracellular antigen Group of T cells is also responsible for stimulating B cells to produce the allergic type of antibodies responsible for allergic diseases