D’YOUVILLE COLLEGE BIOLOGY 307/607 - PATHOPHYSIOLOGY Lecture 5 - IMMUNE RESPONSES, IMMUNIZATION Chapter 5 1. Antibody-Mediated Immunity (AMI): • antibodies – Y-shaped protein molecules produced by B cells - secreted by stimulated mature B cells (plasma cells) & freely circulate in plasma as immunoglobulins - FC fragment (= stalk of Y) binds to surfaces of defensive cells that express FC receptors (e.g. phagocytes, mast cells, NK cells) - different classes of antibody (immunoglobulin) have different FC fragments - FAB fragments (= branches of Y) bind to unique epitope of antigens - antigen-antibody binding results in: - neutralization of toxins - agglutination (clumping) of cell-bound antigens - precipitation of soluble antigens - complement fixation - above results promote phagocytosis (opsonization), inflammation (stimulation of mast cells, chemotaxis) and lysis of offending cells (activated complement and activated NK cells) (figs. 5 – 3, 5 – 6 & ppts. 1 & 2) • immunoglobulins (fig. 5 – 5 & ppt. 3) – freely circulating antibodies constitute a fraction of plasma proteins - five categories (ppts. 4 & 5) – IgM (pentamer - fig. 5 – 4), IgG (commonest), IgA (often a dimer – found in external secretions), IgE (low concentration, involved in parasitic infections and in allergies), & IgD (lymphocyte antigen receptor) - IgM produced first in initial response (mainly to bacterial infections), followed by IgG; both are complement-fixing antibodies; IgM is dominant in agglutination reactions; secondary response produces mainly IgG - IgE binds (via Fc component) to eosinophils to promote anti-allergen & anti-parasitic reactions Bio 307/607 lec 5 - p. 2 - Bio 307/607 lec 5 - p. 3 - • sensitization: - B cells activated by antigen binding proliferate a population of plasma cells (secrete antibodies specific for stimulating antigen) as well as ‘memory’ cells (ppt. 6) - antibody titer (specific for activating antigen) rises (fig. 5 – 10 & ppt. 7) - B cell activation is facilitated by lymphokines (interleukins) from activated T helper cells (TH2) - clonal expansion (plasma & memory cell formation) can be undertaken by B cells with or without the intervention of helper T cells - once established, the specific B cell clone can respond more rapidly and vigorously on subsequent encounters (immunological learning & memory) - antigen-presenting cells (APC) are cells that have phagocytized or bound antigen (macrophages, B cells, dendritic cells) - antigens are presented on surface in association with MHC markers (class II) (ppt. 8) - T cells (specific clone that can bind to the MHC as well as to the displayed antigen) are activated by antigen recognition (clonal selection) - APCs secrete interleukin 1 that stimulates proliferation of a clone of active helper cells as well as ‘memory’ cells (known as clonal expansion; see figs. 5 – 8, 5 – 9 & ppts. 9 & 10) 2. Cell- Mediated Immunity: • TH1 cells interact with APCs and undergo clonal expansion (fig. 5 – 8 & ppts. 9 & 10) - these helper cells facilitate clonal expansion or other cells specific for same antigen via secretion of lymphokines - cell types stimulated by lymphokines include cytotoxic T cells, NK cells & macrophages (fig. 5 – 11 & ppts. 11 - 13) Bio 307/607 lec 5 - p. 4 - - activated TC-cells recognize & kill virus-infected or parasite-infected cells, which display antigen in association with MHC class I molecules (bind with Tcell receptor aided by CD8) (ppt. 14) - activated NK cells recognize & kill virus-infected cells & tumor cells (tumor surveillance) (ppt. 15) - healthy cells display MHC I alone & inhibit NK cell activity, whereas antigen in association with MHC class I elicits cytotoxic response from NK cells • summary (ppts. 16 & 17) 3. Active and Passive Immunization: • vaccination: active immunization with sensitizing dose of antigen - vaccines (table 5 - 3) are prepared from dead microorganisms, weakened microorganisms (attenuated), or inactivated exotoxins of microorganisms - administration of vaccine elicits primary immune response so that subsequent natural exposure to the antigen will be vigorously and rapidly dispatched; an otherwise dangerous or lethal first encounter can be avoided • antiserum administration: passive immunization with antibodies from donor with immunity or manufactured antibodies (monoclonal antibodies) - provides temporary protection from infective organisms or their toxins, e.g. inoculations for travelers to exotic locations - provides protection during immune system’s development of sensitization to an infection, e.g. rabies shots - may be used to prevent sensitization to Rh incompatibility between mother and fetus, e.g., administration of anti-Rh following any birth involving Rh incompatibility (fig. 5 – 13 & ppt. 18)