Microbiology Chapter 16: The Adaptive Immune ResponseA Glimpse of History - Diphereriao Infection that caused obstruction of the airway in small childreno Infected animals that recovered where re-exposed to the antigen and showed no illness Discovery of antibodies in the bloodAdaptive Immune Response- 1.Primary response o to particular antigeno may take a week or more to developo during this time, innate immunity may/may not suffice\- 2.Secondary (anamnestic) response - latero to same antigeno immune system ‘remembers’ antigen on subsequent exposure ==> enhanced responseTwo Categories of Immune Defense- .Humoral immunity – mediated by antibodieso to eliminate extracellular antigenso bacteria, viruses, toxins in fluids around tissues, bloodstreamo antibodies can bind to the receptors, stopping the cell from entering a body tissue or cell- Cellular immunity - mediated by cellso to eliminate intracellular antigenso Ex. viruses inside cellsTypes of Lymphocytes- Cellular immunity – eliminating intracellular antigenso mediated by T lymphocytes = “T cells”o mature in thymuso don’t recognize free antigens (outside the cell)o antigen must be “presented” on a host cell surfaceto T-cell receptors (similar to B-cell receptors) on T-cello second opinion to T-cells provided by dendritic cells (innate immunity) the APCo 2 subsets of T cells eliminate antigen (and form memory cells): cytotoxic T cells (“killer” cells) helper T cells- 3rd type: regulatory T cellso prevent response against self i.e. auto-immune diseases The Lymphiod Systemo system of tissues and organs which bring B and T cells in close contact with antigens therefore stategically-located in bodyo lymph = fluid formed as result of circulatory system oxygen-rich, nutrient-rich fluid leaves blood, filters into tissues most depleted fluid returns to bloodstream some collected by lymphatic system = lympho lymph travels to lymph nodes where antigens and T and B cells make contact protein, cells removed fluid portion empties back into bloodstream behind left collarbone- Secondary Lymphoid organs where lymphocytes gather to encounter captured antigens Lymph nodes  Spleen Tonsils… MALT mucosal-associated lymphoid tissue (a network of lymphatic tissue)- Ex. Peyer’s patches sample the small intestine which allow the presentation of an antigen to lymphocytes below the mucsal layer and transfer it to the cells beneath- An important role in mucosal immunity the prevents microbes from invading mucus membranes SALT skin-associated lymphoid tissues - Lymphoid tissues under skin ONLY organs where adaptive response can be triggered - thus their strategic locations in body- Primary Lymphoid Tissueso Red bone marrow and the thyroido Where the T and B cells mature The Nature of Antibodies- Y-shaped proteins- Four protein chains held together by disulfide bondso 2 heavy undergo more frameshift mutations o 2 lighto Each heavy and light chain has a Constant region (fc)o Each heavy and light chain has a Variable region (Fab)o Variable region unique => binds a specific antigen- Also called imunoglobulins, have two indentical arms (Fab regions) and the stem (Fc region)o Fab are antigen bindingo Fc are fragments that cen be crystallized - Antibody Actionso Neutralization prevents toxin/virus from binding to cello Immobilization & prevention of adherence blocks function/bindingo Agglutination & precipitation clumped bacteria more easily phagocytizedo Opsonization coated bacteria more easily phagocytized done by c3b complimentso Complement is activated bound antibody triggers Classical pathway that triggers compliment cascade results in things like the membrane attack complexo Cellular cytotoxicity (antibody Dependent cellular cytotoxicity) cell carrying antibodies is a target for immune cells e.g. natural killer (NK) cells NK cells that directly kill the cell- Immunoglobulin classeso All are monomers except for one which is a polymer. Function of IgD is still not clear.o IgM: pentamer; functions as part of B cell receptors, which perform initial antigen binding Ten antigen binding sites that have a great chance at agglutination, precipitation and nueralizationo IgG: monomer; most abundant Memory antibody that is passed into the womb in passive immunityo IgG and IgM are most abundant; provide majority of specific immune response to microbeso IgA: protects epithelial linings of tracts exposed to exterior of body  directly neutralize toxins, viruses block bacteria from binding host cells mucosal immunity that is a dimmer (secretion) and monomer (serum)o IgE: attracts eosinophils; stimulates release of histamines by basophils and mast cells Involved in defense against parasitic worms and other multicellular parasites Stimulates the release of histamine by the stimulation of basophils and mast cells Nature of Antigens- (Ag) = Antibody generator = immunogeno any compound that elicits an immune responseo huge variety: pathogenic bacteria and viruses, toxins, transplanted organs, plant pollens…- In generalo proteins, polysaccharides => strongly antigenico lipids, nucleic acids often not- recognition is via antigenic determinant/epitopeo epitope = short peptide sequence or a shapeClonal Selection of the Lymphocyte- When antigen enters body, only B cells making appropriate antibody can bindo clonal selection- These cells proliferate extensivelyo clonal expansiono Without sustained stimulation, B cells undergo apoptosis which limits the immune response (a good thing)- Clonal selection theory is the theory that only the antigen binding cell will clone because it is neededB lymphocytes and the antibody response- B lymphocytes produce antibodies that bind to antigens and tag them for destruction by other meanso cellular immunity attacks the enemy cells directly- Recognition phaseo begins when an antigen binds to several surface receptors on immunocompetent B cell taken into the cell by receptor-mediated endocytosis After endocytosis, B cell processes (digests) the antigen Links the epitopes to its MHC–II proteins and displays on surface These antigen specific receptors are identical to the same antigen-specific antibody that the B cell will later release  antigen help link together receptors  B cell is now an APC- Activation phaseo a helper T cell activates a B cell by binding to the antigen–MHC IIprotein complex on