Fundamentals of Adaptive Immunity: Lymphocytes, Antibodies, and MHC

ADAPTIVE IMMUNITY B lymphocytes • B lymphocytes differentiate into plasma cells to secrete antibody when stimulated • B cell with a receptor for virtually every foreign antigen → receptor on surface is the antibody that will later be secreted in large quantities once the cell is stimulated T lymphocytes (2 main types) • T helper cell (CD4): directs other cells to perform effector functions • T suppressor cell (CD8): performs an effector function when stimulated by killing cells that have been infected with viruses • Contain receptors on their surface that recognise virtually every foreign antigen Natural killer cells • Lymphocytes that are part of the innate immune response → do not display antigen-specific receptors • Key role in surveillance for abnormal cells in body e.g. tumour cells, virus infected cells Lymphocyte receptors • Each naïve lymphocyte bears receptors with one single specificity • During development (bone marrow [B] and and thymus [T cells]), millions of genetic recombinations occur in genes that encode lymphocyte receptors → lymphocyte clone is present to recognise almost every antigen • Self-tolerance: lymphocytes that are potentially self-reacting undergo clonal deletion during development Antibodies • Constant region: limited number of forms, functions to dispose of antigen once bound • Variable region: combines with antigen, is antigen-specific → millions of variations • Neutralisation: antibodies block pathogen entry into cell by combining with them • Opsonisation: constant region of antibody molecule is recognised by phagocytes → will destroy antigen when attached to antibody • • Complement cascade: antibodies bound to antigen form a receptor for the first component of complement → once C1 is activated, a cascade of enzymatic reactions occurs Humoral immunity: adaptive immunity involving B cells and antibodies Clonal expansion in adaptive immunity • When a naïve circulating lymphocyte is presented with its specific antigen by an APC (antigen presenting cell) it stops circulating, becomes larger, and turns into a lymphoblast → lymphoblast begins a phase of rapid division (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 → direct other cells or destroy infected cells • Activated lymphocytes 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 2nd signal for T cell → T cell provides 2nd signal for B cell Immunological memory • Most effector lymphocytes undergo apoptosis after infection, but some remain as memory cells • Memory cells allow immune system to recognise a re-infection more promptly → mount an effective immune response sooner → basis of immunization Cell-mediated immunity • Viruses (+ some bacteria and other pathogens) are located within host cells → out of reach of antibodies • Antigens derived from replicating virus within a cell are displayed on the cell surface → recognised by effector T cells that then destroy the cell TH1 and TH2 cells • Some pathogens, when engulfed by macrophages, are incorporated into lysosomes (enzymes destroy it) • 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 + also activated other bactericidal mechanisms o Also release chemo-attractants for recruitment of further macrophages • The TH2 subset of CD4 lymphocytes act to stimulate B cells to produce immunoglobulin o The immunoglobulin (antibody) can destroy extracellular antigen o This group of T cells is also responsible for stimulating B cells to produce the allergic type of antibodies responsible for allergic diseases Major histocompatibility complex (MHC) • Glycoprotein molecules capture foreign antigens within the cell and display fragments of these foreign antigens on the cell surface for interaction with T lymphocytes → encoded by cluster of genes = the MHC • 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 molecules combine with viral particles (produced in cytoplasm) – display antigens on surface • o MHC Class I molecules are recognised by CD8 T cells MHC Class II molecules combine with antigen fragments that are contained within vesicles within cells. This includes antigen bound by antibody after the macrophage has engulfed it o MHC Class II molecules are recognised by CD4 T cells T cells must express both the antigen receptor, and a 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.