Immunology lec

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<ul><li><p>INTRODUCTION TO IMMUNOLOGY</p></li><li><p>IMMUNOLOGY AND THE IMMUNE SYSTEMImmunologyStudy of the components and function of the immune system</p><p>Immune System Molecules, cells, tissues and organs which provide non-specific and specific protection againstMicroorganismsMicrobial toxinsTumor cellsCrucial to human survival</p></li><li><p>THE IMMUNE RESPONSE AND IMMUNITYImmune responseInnate (non-specific)Adaptive (specific)Primary Secondary</p><p>ImmunityState of non-specific and specific protection</p><p>Acquisition of ImmunityNaturalArtificial</p></li><li><p>NATURALLY ACQUIRED IMMUNITYActiveAntigens enter body naturally with response ofInnate and adaptive immune systemsProvides long term protection</p><p>PassiveAntibodies pass from mother toFetus across placentaInfant in breast milkProvides immediate short term protection</p></li><li><p>ARTIFICIALLY ACQUIRED IMMUNITYActiveAntigens enter body through vaccination with response ofInnate and adaptive immune systemsProvides long term protection</p><p>PassiveAntibodies from immune individuals injected into bodyReferred to asImmune serum globulins (ISG)Immune globulins (IG)Gamma globulinsProvides immediate short term protection</p></li><li><p>PRINCIPAL FUNCTION OF THE IMMUNE SYSTEMTo protect humans from pathogenic microorganisms </p><p>Pathogenic microorganisms (Pathogens)Microorganisms capable of causing infection and/or disease</p><p>InfectionAbility of pathogen to enter host, multiply and stimulate an immune response</p><p>DiseaseClinical manifestations associated with infection</p></li><li><p>BACTERIA, VIRUSES, FUNGI, PARASITESOH MY!Streptococcus pyogenes (Group A Streptococcus)Klebsiella pneumoniaeMycobacterium tuberculosisEbola virusHuman Immunodeficiency Virus (HIV)Aspergillus fumigatusCandida albicansCryptococcus neoformansCryptosporidium parvumStronglyoides stercoralisAscaris lumbricoidesPlasmodium falciparum</p></li><li><p>DEFENSE MECHANISMS OF THE HUMAN HOSTInnate Mechanisms (Innate immunity)First line of defenseNon-specific</p><p>Adaptive Mechanisms (Adaptive immunity)Second line of defenseHighly specific with memory</p><p>Cooperation between mechanisms</p></li><li><p>THE CLUSTER OF DIFFERENTIATION (CD) A protocol for identification and investigation of cell surface molecules</p><p>CD number assigned on basis of 1 cell surface molecule recognized by 2 specific monoclonal antibodies</p><p>CD nomenclature established in 19821st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA)</p></li><li><p>THE CLUSTER OF DIFFERENTIATION (CD) CD markers on leukocytes</p><p> Granulocyte CD45+, CD15+ Monocyte CD45+, CD14+ T lymphocyte CD45+, CD3+ T helper lymphocyte CD45+, CD3+, CD4+ T cytotoxic lymphocyte CD45+, CD3+, CD8+ B lymphocyte CD45+, CD19+ Natural killer cell CD45+, CD16+, CD56+, CD3-</p></li><li><p>THE LYMPHATIC SYSTEMLymphFluid and cells in lymphatic vessels</p><p>Lymphatic vesselsCollect and return interstitial fluid to bloodTransport immune cells throughout bodyTransport lipid from intestine to blood</p><p>Lymph nodes Kidney shaped organs at intervals along lymphatic vessels</p><p>Other secondary lymphatic tissues and organs</p></li><li><p>LYMPHOCYTES AND THE LYMPH NODESNave lymphocytes circulate between blood, lymph and secondary lymph nodes</p><p>Pathogens from infected tissue sites are picked up by lymphatic vessels and arrive at closest lymph node</p><p>T and B cells congregate at specific regions of nodes</p><p>Architecture and size of nodes change in response to activation of lymphocytes</p></li><li><p>LYMPHOCYTES AND THE SPLEENSpleenLymphoid organ in upper left abdomenFunctionsRemove damaged or old erythrocytesActivation of lymphocytes from blood borne pathogens</p><p>Architecture of SpleenRed pulpErythrocytes removedWhite pulpLymphocytes stimulated</p></li><li><p>SECONDARY LYMPHOID TISSUES ASSOCIATED WITH MUCOUS MEMBRANESPrimary portals of entry for pathogensRespiratory tractGastrointestinal tract</p><p>Secondary lymphoid tissuesBronchial-associated lymphoid tissue (BALT)Gut-associated lymphoid tissues (GALT)Tonsils, adenoids, appendix, Peyers patches</p><p>Pathogens are directly transferred across mucosa by M cells</p></li><li><p>THE INNATE IMMUNE RESPONSEMediated (initiated) by phagocytes, NK cells and soluble proteinsPhagocytesCells specialized in the process of phagocytosisMacrophagesReside in tissues and recruit neutrophilsNeutrophilsEnter infected tissues in large numbersRecognize common molecules of bacterial cell surface using a few surface receptorsPhagocytosisCapture, engulfment and breakdown of bacterial pathogen</p></li><li><p>THE INNATE IMMUNE RESPONSEInflammatory response enhances phagocytosis through acute phase proteinsMannose-binding lectin (MBL)Binds to bacterial surface with particular spatial arrangement of mannose or fucoseC-reactive protein (CRP)Binds to phosphorylcholine on bacterial surfaceComplementSet of proteins which bind to bacterial surfaceInflammatory responseAccumulation of fluid and cells at infection site (swelling, redness, heat and pain)</p></li><li><p>THE ADAPTIVE IMMUNE RESPONSECreates millions of different B and T cells for specific antibody-mediated and cell-mediated immunityAntibody-Mediated Immunity (AMI)Involves B lymphocytes, plasma cells and antibodiesHumoral immunityName derives from antibodies found in body fluids (humors - old medical term)Cell-Mediated Immunity (CMI)Involves T lymphocytes, antigen-presenting cells and MHC (major histocompatibility complex) moleculesCellular immunity</p></li><li><p>ANTIBODY-MEDIATED (HUMORAL) IMMUNITYDirected against extracellular microorganisms and toxins</p><p>B-lymphocytes (B cells)Differentiate into plasma cells which produce antibodiesFunction as antigen-presenting cells (APCs)</p><p>Classification of Antibodies (Immunoglobulins)Immunoglobulin M (IgM)Immunoglobulin G (IgG)Immunoglobulin A (IgA)Immunoglobulin D (IgD)Immunoglobulin E (IgE)</p></li><li><p>CELL-MEDIATED IMMUNITY (CMI)Directed against intracellular microorganisms Non-phagocytic cells and phagocytic cells</p><p>T-lymphocytes (T cells)Differentiate into effector cells following antigen presentation by antigen presenting cells (APCs)</p><p>Functional types of T cellsHelper (CD4 T cells)TH1 and TH2 cellsCytotoxic (CD8 T cells)Regulatory CD4 and CD8 Tregs </p></li><li><p>THE NATURE OF ANTIGENSHistorically named as antibody generatorsMolecule which stimulates production of and binds specifically to an antibodyContemporary view distinguishes betweenAntigenMolecule which can bind to specific antibody but cannot elicit adaptive immune responseImmunogenMolecule which can stimulate adaptive immune responseBest immunogens are proteins with MW &gt; 10,000</p></li><li><p>THE NATURE OF ANTIGENSCarbohydrates, nucleic acids and lipids are also potential antigens / immunogensHaptenSmall (low MW) molecule unable to elicit immune responseCombines with larger carrier molecule which together function as immunogenAntibody may react independently with hapten following hapten/carrier adaptive immune responseExamplePenicillin G (MW of 372)Albumin (MW of 66,000)</p></li><li><p>THE NATURE OF ANTIBODIESAntibodies are glycoproteinsExist as monomers, dimers or pentamers of basic structureBasic antibody structure has 4 polypeptide chains2 identical light chains2 identical heavy chainsRegions of heavy and light chainsVariableConstant</p></li><li><p>THE NATURE OF ANTIBODIESAlso referred to asImmune globulins / Immunoglobulins (IG)Immune serum globulins (ISG)Gamma globulinsContemporary immunologyAntibodySecreted form of IG made by plasma cellsImmunoglobulinAntigen binding molecules of B cells (B cell antigen receptors)</p></li><li><p>CLASSIFICATION OF ANTIBODIES (IMMUNOGLOBULINS)Five (5) classes (isotypes)Immunoglobulin A (IgA)Immunoglobulin G (IgG)Immunoglobulin M (IgM)Immunoglobulin D (IgD)Immunoglobulin E (IgE)Based on structural differences in constant regions of heavy chainsClasses have specialized effector functions</p></li><li><p>B LYMPHOCYTES AND HUMORAL IMMUNITYOriginate from stem cells in bone marrow</p><p>Maturation in bone marrow followed by migration to secondary lymphoid tissue</p><p>Antigen exposure in secondary lymphoid tissue</p><p>Following exposure to antigen, differentiation into plasma cells and memory cells</p><p>Plasma cells produce antibodies of all IG classes</p></li><li><p>ACTIVATION OF ANTIBODY PRODUCING CELLS BY CLONAL SELECTIONB lymphocytes recognize intact pathogenic microorganisms and toxins</p><p>B lymphocytes possess specific surface receptors for recognition of specific antigenIgM and IgD</p><p>Binding of specific antigen results in proliferation of a clonal population of cells</p><p>Antigen determines clonal proliferation</p></li><li><p>ACTIVATION OF ANTIBODY PROCDUCING CELLS BY CLONAL SELECTIONProliferation of activated cells is followed by differentiation intoPlasma cellsLife span of4 to 5 days1 to 2 monthsProduce 2,000 antibody molecules / secondMemory cellsLife span of years to decadesDifferentiate into plasma cells following stimulation by same antigen</p></li><li><p>PRIMARY AND SECONDARY ANTIBODY RESPONSEPrimary ResponseFollowing exposure to an antigen, there is a slow rise in IgM followed by a slow rise in IgG</p><p>Secondary ResponseFollowing exposure to previously encountered antigen, there is a rapid rise in IgG and slow or no rise in IgMMemory or anamnestic response</p></li><li><p>T LYMPHOCYTES AND CELL-MEDIATED IMMUNITYOriginate from stem cells in bone marrow followed by migration to thymus glandMaturation takes place in thymus gland followed by migration to secondary lymphoid tissueRespond to antigens on the surface of antigen presenting cells (APCs)Antigen presenting cells (APCs)MacrophagesDendritic cellsB lymphocytes</p></li><li><p>T LYMPHOCYTES AND CELL-MEDIATED IMMUNITYAntigen presenting cells (APCs)Ingest and process antigens then display fragments (short peptides) on their surface in association with molecules of major histocompatibility complex (MHC)Major histocompatibility (MHC) moleculesMHC class I moleculesPresent antigens to CD8 T cellsMHC class II moleculesPresent antigens to CD4 T cellsT cells which encounter antigen differentiate into effector T cells</p></li><li><p>ROLES OF EFFECTOR T CELLS IN IMMUNE RESPONSECD8 cytotoxic T cellsEnter bloodstream and travel to infection siteKill cells infected with viruses and other intracellular microorganismsCD4 TH1 helper T cellsEnter blood stream and travel to infection siteHelp activate macrophagesCD4 TH2 helper T cellsWork within secondary lymphoid tissuesHelp activate B cells</p></li><li><p>DISORDERS OF THE IMMUNE SYSTEMHypersensitivity ReactionsOver-reaction of adaptive immune response to harmless antigensFour Types of reactions (I- IV)AutoimmunityMisdirected adaptive immune responseResults from a loss of self-toleranceThree Types (II, III, IV) of reactionsImmunodeficienciesComponents of immune system either absent or defectiveGenetic or acquired etiology</p></li><li><p>IMMUNOLOGY FOR DIAGNOSIS OF DISEASESAnalytical methods using either antibody or antigen with an indicator system for detecting specificAntibodiesDetected using antigens or antibodyAntigensDetected using antibody</p><p>Indicator systemsLatex particles (colored)Microspheres (colored) conjugated with antibodyEnzymes conjugated to antibodyFluorochromes conjugated to antibodyNitrocellulose membranes fixed with antigen or antibody</p></li><li><p>METHODS IN DIAGNOSTIC IMMUNOLOGYLatex agglutination (LA)Latex particles (dyed) coated with antigen, antibody or?Read visually for clumping of latex particles</p><p>Staphyloslide (Becton Dickinson)Identification of Staphylococcus aureusStaphylococcus aureus producesCoagulase (bound and free)Protein ABlue latex particles coated and not coated withFibrinogenIgG</p></li><li><p>METHODS IN DIAGNOSTIC IMMUNOLOGYImmunochromatographic assay (ICA)Antibody or antigen immobilized (Test line)Antibody immobilized (Control line)MembranesNitrocellulose, cellulose acetateRead visually for colored test and control linesExamplesGroup A Streptococcus (GAS) antigenInfluenza A and B antigensRespiratory syncytial virus (RSV) antigenRotavirus antigenHIV-1/2 antibody</p></li><li><p>PRINCIPLES OF OraQuick RAPID HIV-1/2 ICA ANTIBODY TESTAntigens and antibody immobilized onto nitrocellulose membrane in T and C zones</p><p>Test (T) Zone Synthetic peptides from HIV envelope region</p><p>Control (C) ZoneGoat anti-human IgG</p><p>Developer solution Facilitates flow of specimen onto test stripRehydrates protein-A gold colorimetric reagent </p></li><li><p>IMMUNOLOGY FOR PREVENTION OF DISEASEHepatitis BPre-exposure prophylaxisVaccination with hepatitis B surface antigen (HBsAg)</p><p>Post-exposure prophylaxisAdministration of Hepatitis B Immune Globulin (HBIG) HumanPurified IgG antibody from plasma of donors with high titer of antibody to the hepatitis B surface antigen (anti-HBs)</p></li><li><p>IMMUNOLOGY FOR TREATMENT OF DISEASERheumatoid ArthritisRemicade (Infliximab)IgG kappa monoclonal antibody against tumor necrosis factor alpha (TNF-alpha)</p><p>Breast CancerHerceptin (Trastuzumab)IgG kappa monoclonal antibody against human epidermal growth factor receptor 2 (HER2)</p></li><li><p>*****************************************************</p></li></ul>