"SLE334 Medical Microbiology and Immunology, T2, 2017Topic 2: The Defence – Host DiseasesAdaptive Responses(Mims’ Chapter 10)Lecture 7Thursday 27 July 2017LT13 (HC2.005), 1-2pm(date, time and venue different for Geelong students)Dr Sharon La [email protected] Medical Microbiology and Immunology, T2, 2017Adaptive Responses SLE334 Medical Microbiology and Immunology, T2, 2017This lecture will cover……•? Antibodies- structure- classes- function / role in defense against infection•? T-lymphocytes- types- T cell receptor- MHC molecules- cellular defense against viral infection•? Defense of mucosal surfaces•? Integration of antibody with innate immune mechanismsSLE334 Medical Microbiology and Immunology, T2, 2017Types of immune responses: Innate and Adaptive. Humoral vs. Cell-Mediatedhttp://www.youtube.com/watch?v=rp7T4IItbtM&feature=channel&list=UL SLE334 Medical Microbiology and Immunology, T2, 2017© 2011 Kenneth Todar, PhD; http://www.textbookofbacteriology.net/innate.htmlTodar's Online Textbook of Bacteriology.SLE334 Medical Microbiology and Immunology, T2, 2017Reminder…. SLE334 Medical Microbiology and Immunology, T2, 2017The role of antibodies•? Antibodies are immunoglobulin moleculessynthesized by host B lymphocytes (which mature inthe bone marrow) when they make contact with aninfectious microbe, which acts as a foreign antigen.•? Antibodies (Ab) act as adaptors to focus acuteinflammatory reactions•? Ab complexed with antigen (Ag) activates “classical”complement pathway•? Acute inflammatory reaction also initiated by Ab bound tomast cells•? Ag-Ab complexes activate phagocytic cells•? Abs block microbial interactions by combining with one ofthe reacting moleculesSLE334 Medical Microbiology and Immunology, T2, 2017Structure of immunoglobulins (Ig)http://www.youtube.com/watch?v=mIQBBgAcSdI SLE334 Medical Microbiology and Immunology, T2, 2017Structure of immunoglobulins (Ig)Figure 10.1 The basic structure of IgGs is a unit consisting of two identicallight polypeptide chains and two identical heavy polypeptide chains linkedtogether by disulfide bonds (black bars). •? Each chain is made-up of individual globular domains. •? Different antibodies have different V and V domains, the highly variableL H regions of the light and heavy chains, respectively. •? This hypervariability is confined to three loops on the V and three on theL V domains. H•? These make up the antigen-binding site (highlighted in red).- antibodies of different antigen specificities each have a unique amino acidsequence in this region•? Each antibody has two identical recognition sites that arecomplementary in shape to the surface of the foreign antigen and whichenable it to bind with varying degrees of strength to that antigen.SLE334 Medical Microbiology and Immunology, T2, 2017Figure 10.2. Ab adaptor molecule2143•? antibody bound to the microbe activates complement and initiates an acute inflammatory reaction.•? C3b generated fixes to the microbe and, together with the antibody molecules, facilitatesadherence to Fc and C3b receptors on the phagocyte and then microbial ingestion. SLE334 Medical Microbiology and Immunology, T2, 2017http://www.studyblue.com/notes/note/n/biol-3240-ch-2-/deck/5465895SLE334 Medical Microbiology and Immunology, T2, 2017Complement pathwaysFigure 10.3. Comparison of the alternative, classical and mannose-binding lectin complementpathways. •? complex of antibody or mannose binding lectin (MBL) with microbial antigen activates thefirst component of the 'classical' pathway (step 1) leading to cleavage of C3 through theC4b2b C3 convertase.SLE334 Medical Microbiology and Immunology, T2, 2017C3-coated salmonella flagella•? flagella have been incubated with anti-flagellum antibody and complement. •? electron-dense material extending 30 nm on either side of each flagellum is believed to be C3b. •? complement fixation by antibody results in a heavy coating of C3b on membranes to whichcomplement has been fixedSLE334 Medical Microbiology and Immunology, T2, 2017Mast cell degranulationFigure 10.5 Degranulation ofmast cells by interaction ofmicrobial antigen with specificantibodies of the IgE class,which bind to specialreceptors on the mast cellsurface. •? The cross-linking ofreceptors caused by thisinteraction leads to therelease of mediators, whichinduce an increase invascular permeability andattract polymorphs, i.e.they provoke an acuteinflammatory reaction atthe site of the microbialantigen. SLE334 Medical Microbiology and Immunology, T2, 2017Activation ofthe alternativecomplementpathwaySLE334 Medical Microbiology and Immunology, T2, 2017Activation of phagocytic cellsFigure 10.6. Antigen-antibody complexes activate phagocytic cells. Other sites on the Fc backbone of certaintypes of antibody molecule bind to specialized Fc receptors on the surface of phagocytic cells. •? If there is more than one antibody in the antigen-antibody complex, these receptors are cross-linked inducingthe cell to put out arms of cytoplasm, which enclose the complex in a phagocytic vacuole. SLE334 Medical Microbiology and Immunology, T2, 2017Abs block microbial interactionsFigure 10.7. Antibodies block microbial interactions by combining with one of the reacting molecules.•? Eg antibody directed against the influenza hemagglutinin prevents the virus from attaching to its specificreceptor on a cell, making it unable to infect that cell. •? antibodies to an essential transport molecule on a bacterial surface can prevent the uptake of that nutrient andcause a metabolic block.•? antibody to a bacterial toxin will prevent damage to the cells with which the toxin would otherwise interact. SLE334 Medical Microbiology and Immunology, T2, 2017Summary:The role of antibodies•? Antibodies (Ab) act as adaptors to focus acuteinflammatory reactions•? Ab complexed with antigen (Ag) activates“classical complement” pathway•? Ab binding to mast cells initiates acuteinflammatory reaction•? Ag-Ab complexes activate phagocytic cells•? Abs block microbial interactions by combiningwith one of the reacting molecules SLE334 Medical Microbiology and Immunology, T2, 2017The role of T lymphocytes•? Defense against intracellular organisms•? Bind to peptide derived fromintracellular organisms complexed withmajor histocompatibility (MHC) complex•? Help macrophages kill intracellularparasites•? Inhibit intracellular replication of virusesSLE334 Medical Microbiology and Immunology, T2, 2017Figure 10.8. Majorhistocompatibilitycomplex (MHC)moleculesProteins derived fromdead organisms and newlysynthesized viral proteins,are fragmented byintracellular cytosolicenzymes, and the peptidesbind to a molecule of themajor histocompatibilitycomplex (MHC).•? act as cellular surfacemarkers "