5 Antigen recognitionAffinity the strength of the binding between an antibodies binding site and a single epitopeAvidity the functional affinity depends on the number of binding sites on the antibody and their ability to react with multiple epitopes
6 Antibody IsotypesIgG Neutralization, opsinization, classical complement pathway, ADCC, passive immunityIgM Pentamer activation of the classical complement pathwayIgA Dimer Mucosal immunityIgE Mast cell degranulation and parasite killing by eosinophils
7 Toxin neutralizationBinding of antibody to a toxin preventing the toxin from receptorsExamples tetanus toxinAbbas and Lichtman 2nd addition Basic Immunology
8 Antibody Function Neutralization Abbas and Lichtman 2nd addition Basic Immunology
9 Neutralization Not all antibodies can neutralize viruses There is a difference in binding and neutralizationExample: GP120 HIV antibodies can bind but not neutralize HIVWhy? There are certain epitopes that are neutralizing
10 Methods to detect different antibodies functions ELISA assays detect antibody antigen bindingVirus neutralization assays detect antibodies that prevent viral infectionThese two assays can give different results from identical serum samples
11 OpsinizationAntibodies coat microbes and promote their ingestion by phagocytesSplenectomy leads to increased susceptability to disseminated infections by encapsulated bacteriaReason: The spleen contains phagocytes and is the major place where phagocytic clearance of opsinized bacteria take place
12 Roitt, Brostoff, Male Fourth Edition Immunology
13 OpsinizationAbbas and Lichtman 2nd addition Basic Immunology
14 Fc ReceptorsFcγRI on Macrophages, neutraphils and eosinophils used for phagocytosis and activation of phagocytosisFcγRIIA on Macrophages, neutraphils and eosinophils and platlets used for phagocytosisFcγRIIB on B lymphocytes used for feedback inhibitionFcγRIIIA on NK cells used for ADCCFcεRI on Mast cells, basophils and eosinophils used for cell activation
15 ADCCAbbas and Lichtman 2nd addition Basic Immunology
16 IgE Mediated killing of parasites Abbas and Lichtman 2nd addition Basic Immunology
17 Complement A collection of proteins that help in host defence A sequential sequence of proteolytic cleavage of these proteins lead to the elimination of microbesPart of the innate immune system, with evolved mechanisms of self/non-self discriminationThree pathwaysAlternativeClassicalLectin
18 Abbas and Lichtman 2nd addition Basic Immunology
19 Proteins in the early stages of complement (alternative pathway) C3 -Serum protein in plasmaLow levels of C3 are spontaneously hydrolyzed in plasma to C3b and C3a, where its products are unstable and break downC3a stimulates inflammationFactor B broken down to Bb fragment forming C3bBb complex (C3 convertase)Factor D plasma serine protease that cleaves factor BProperdin stabilizes the C3bBb convertaseC3bBbC3b is a C5 convertase
20 Proteins in the early stages of complement (classical pathway) C1(C1q, C1r, C1s) initiates the classical pathway, binds the Fc antibody region protease for C4 and C2C4 C4b binds to the surface where antibody is bound, C4a stimuates inflammationC2 binds to C4 where C2a is cleaved by C1 and forms C4b2a (C3 convertase)C4b2aC3b is a C5 convertase
21 Late stages of complement activation Abbas and Lichtman 2nd addition Basic Immunology
22 Proteins in late stages of complement activation C5 C5b initiates assembly of the membrane attack complex (MAC) C5a stimulates inflammationC6 binds C5b and accepts C7C7 component of the MAC inserts in to lipid membranesC8 component of the MAC initiates binding and polymerization of C9C9 component of the MAC polymerizes to form membrane pores
23 Functions of the Complement System Important in elimination of microbes during innate and adaptive immune responsesOpsinizationDirect killing of microbesChemotactic attractionProcessing of immune complexesAugmentation of localization of antigen to B cells and APCs
24 Abbas and Lichtman 2nd addition Basic Immunology
25 Roitt, Brostoff, Male Fourth Edition Immunology
26 Inherited deficiencies of complement C3 deficient susceptible to infections early in life usually fatalC2 and C4 deficient are normal, indicating that deficiency in the classical and lectin pathways can be overcome by the alternative pathwayC9 MAC deficiency increased Neisseria infections
27 Regulation of Complement Why? To prevent uncontrolled and harmful activationHost cells express regulatory membrane proteinsDecay accelerating factor (DAF)Membrane co-factor protein (MCP)Type 1 complement receptor (CR1)
28 Complement regulatory proteins Abbas and Lichtman 2nd addition Basic Immunology
29 Host plasma complement regulatory proteins C1 Inhibitor inhibits C1r and C1s serine protease activityFactor I cleaves C3b and C4bFactor H causes dissociation of alternative pathway C3 convertase subunits co-factor for factor IC4 binding protein causes dissociation of classical pathway C3 convertase subunits co-factor for factor I
30 Regulation of Complement Abbas and Lichtman 2nd addition Basic Immunology
31 Complement controlHost cells can be overwhelmed by complement activationFor virus neutralization assays it is therefore important to heat inactivate sera to destroy complement activity
32 Inherited deficiencies of complement regulatory proteins Deficiency in C1 inhibitor causes hereditary angioneurotic edema a disease characterized by excessive C1 activation causing edemaDeficiency in glycolipid anchor synthesis results in deficiencies in decay accelerating factor and membrane cofactor protein results in uncontrolled complement activation and lysis of erythrocytes
33 Mucosal ImmunityThe vast majority of pathogens invade at mucosal surfacesBlocking pathogens at the site of infection the mucosal surfaces can prevent infectionIgA can be actively transported to and secreted from mucosal surfacesIgA can be transported from the lamina propria by the poly-Ig receptor on the basal surface of epithelial cells where it is endocytosed and secreted into the lumen where the poly-Ig receptor is cleaved by a protease
34 Neonate immunityIn humans maternal antibodies are actively transported across the placenta (Passive immunity)In some other animals (cattle) maternal antibodies do not cross the placentaAntibodies are passively transferred in milkThe presence of maternal antibodies can inhibit immune responses to vaccines
35 Evasion of humoral immunity by microbes Antigenic variationInhibition of complement activation- Neisseria miningitides sialic acid expression inhibits c3 and c5 convertases-Streptococcus M protein blocks C3 binding and C3b binding to complement receptorsStaphylococcal protein A binding FC of ABsStreptocoocal protein G binding FC of ABsResistance to phagocytosis Pneumococcus
36 Discussion QuestionsWhat regions of antibodies are involved in the functions of antibodies?
37 Discussion QuestionsHow do heavy chain class switching and affinity maturation improve the abilities of antibodies to combat infectious pathogens?
38 Discussion QuestionsIn what situations does the ability of antibodies to neutralize microbes protect the host from infections?
39 Discussion QuestionsHow is the complement system activated, and why is it effective against microbes but does not react against host cells and tissues?
40 Discussion QuestionsWhat are the functions of the complement system, and what components of complement mediate these functions?
41 Discussion QuestionsHow do antibodies prevent infections by ingested and inhaled microbes?
42 Discussion QuestionsHow do neonatal animals develop the capacity to protect themselves from infections even before their immune systems have reached maturity?
43 Discussion QuestionsWhy are there so many numerous pathways for Ig function?