COLLABORATION OF INNATE AND ADAPTIVE IMMUNITY ANTIBODY STRUCTURE AND FUNCTION 8 th week Physiotherapy BSc 2015 - limited specificity - immediate reaction - does not improve - no memory - highly specific - develops in several days - improves after exposure - has memory IMMUNE SYSTEM Innate / Natural Acquired / Adaptive Cellular Granulocytes Monocytes/Macrophages Natural Killer cells Dendritic cells Mast cells CD4+ (helper) T cells CD8+ (cytotoxic) T cells B cells Plasma cells Humoral Complement proteins Cytokines Acute phase proteins Antimicrobial proteins Antibodies THE EFFECTS OF ANTIGEN-PRESENTING CELLS ON THE ADAPTIVE ARM OF THE IMMUNE SYSTEM THE LOCATION OF INNATE AND ADAPTIVE CELL INTERACTIONS THE EFFECTS OF T CELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM RECEPTORS AND CELL-SURFACE MOLECULES OF MACROPHAGES TLR4 + CD14 MHCI MHCII TLR pattern recognition Rs CR1 (CD35) CR3 (CD11b/CD18) LFA1 (CD11a/CD18) Fc RIII (CD16) Fc RII (CD32) Fc RI (CD64) Ag + IgG complex Mannose receptor Scavenger receptor MM KILLING THROUGH LYSOSOMAL ENZYMES, OXYGEN AND NITROGEN SPECIES Activation of macrophages THE EFFECTS OF B CELLS ON THE INNATE ARM OF THE IMMUNE SYSTEM EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses NEUTRALIZATION OPSONIZATION opsonized phagocytosis (IgG) ADCC (NK cell-mediated killing) (IgG) mast cell degranulation (IgE) COMPLEMENT ACTIVATION Antigen binding Complement binding site Placental transfer Binding to Fc receptors THE CONSTANT REGION OF AN ANTIBODY CAN BIND TO Fc RECEPTORS (FcR) FcR activation occurs when the antibody forms a complex with an antigen Major opsonins: ANTIBODIES Complement molecules Acute-phase proteins (CRP, SAP) Opsonization facilitate and accelerate the recognition of the pathogens by phagocytes Phagocytes must express receptors for the opsonins: IgG Fc RI C3b CR1 RECEPTORS AND CELL-SURFACE MOLECULES OF MACROPHAGES TLR4 + CD14 MHCI MHCII TLR pattern recognition Rs CR1 (CD35) CR3 (CD11b/CD18) LFA1 (CD11a/CD18) Fc RIII (CD16) Fc RII (CD32) Fc RI (CD64) Ag + IgG complex Mannose receptor Scavenger receptor MM Antibodies target virus infected cells, flagging them for the recognition by natural killer (NK) cells ANTIBODY EFFECTOR FUNCTIONS ANTIBODY-DEPENDENT CELL CYTOTOXICITY IgE most important isotype against helminths triggers ADCC by eosinophils mast cells carry high affinity Fc receptors same mechanism in allergic reactions Heavy chain types: IgG - gamma () heavy chains IgM - mu () heavy chains IgA - alpha () heavy chains IgD - delta () heavy chains IgE - epsilon () heavy chains HUMAN IMMUNOGLOBULIN CLASSES Encoded by different heavy chain constant gene segments GC reaction: proliferation (clonal expansion) of activated B cells affinity maturation (stronger binding to epitopes) isotype switch (different effector functions) memory B cell formation (from improved clones) Only by the help of Th cells! ISOTYPE SWITCH heavy chain constant gene segments are divided always the closest to the variable domain is expressed (first always IgM) the switch is driven by the cytokines produced by helper (CD4+) T cells ISOTYPE SWITCHING IS T-DEPENDENT B cell Helper T cell IL-2 IL-4 IL-5 IL-2 IL-4 IL-5 IgM IgG IgA IgE IL-2 IL-4 IL-6 IFN IL-5 TGF IL-4 B cell proliferation, differentiation and isotype switching IgA transport to mucosal surfaces and body secretions Poly Ig receptors for IgA transport across the epithelium to the mucosal surface additional help for the natural barriers of our body defense of the epithelial surfaces mainly neutralization NATURAL PASSIVE IMMUNIZATION Pathological consequences of placental transport of IgG (hemolytic disease of the newborn) Passive anti-D IgG anti-Rh IgM EFFECTOR FUNCTIONS OF ANTIBODIES Antibody-mediated immune responses NEUTRALIZATION OPSONIZATION opsonized phagocytosis (IgG) ADCC (NK cell-mediated killing) (IgG) mast cell degranulation (IgE) COMPLEMENT ACTIVATION ANTIBODY EFFECTOR FUNCTIONS COMPLEMENT FIXATION Binding of complement protein 1 to IgG or IgM immunoglobulins on a bacterial surface ANTIBODY EFFECTOR FUNCTIONS COMPLEMENT FIXATION Complement 1 protein and the immunoglobulin bound to the bacteria cause the binding of more complement proteins ANTIBODY EFFECTOR FUNCTIONS COMPLEMENT FIXATION More complement proteins are recruited leading to the death of the extracellular pathogen (bacteria) by forming pores in it