1. Introduction to Immunology1.1 General Properties of Immune Responses1.1.1 Overview of immune responses in vivo1.1.2 Classification1.1.2.1 innate and adaptive immunityInnate immunityadaptive immunityfeaturesphases1.1.2.2 humoral and cell-mediated immunityhumoral immunitycell-mediated immunity1.1.2.3 active and passive immunity1.2 Components of Immune Systems1.2.1 Tissues and organs of immune systems1.2.1.1 generative organs (primary lymphoid organs)Bone MarrowThymus1.2.1.2 peripheral organs (secondary lymphoid organs)lymph nodesspleencutaneous immune systemmucosal immune system1.2.2 Cells of immune systems1.2.2.1 lymphoid progenitor cells B lymphocytesT lymphocytesNK cellsNKT cells1.2.2.2 myeloid progenitor cellsGranulocytesMast cellsMacrophages(Mononuclear phagocytes )1.2.2.3 Dendritic cells(DC)2. Recognition of Antigens2.1 Innate immune cells and anitgen recognition2.1.1 Pathogen associated molecular patterns(PAMPs)2.1.2 Pattern recognition recptors(PRRs) and signaling pathways2.1.2.1 PPRsMembrane-bound PPRsmannose receptorScavenger receptorToll-like receptor(TLR)Cytoplasmic PRRsNOD Like ReceptorsRIG-I-like RNA helicase(RLH)2.1.2.2 PRR(TLR/RLH) signalling pathwayTLR signaling pathwayAdaptor molecules in the pathwaytwo basic pathways

RLH signaling pathway2.1.3 PAMPs and PRRs interations during viral infections2.1.3.1 TLR/RLH recognition of viral infectionVial recognition by TLRsViral recognition by RLHs2.1.3.2 Viral antagonist of PRR signalling pathways2.1.3.3 The therapeutic application of manipulation of PRR signalling pathways2.2 T Lymphocytes and Antigen Recognition2.2.1 The Major Histocompatibility Complex (MHC molecules)2.2.1.1 Discovery of MHC2.2.1.2 MHC genesProperties of MHC genesGenomic organiztion of MHCExpression and regualtion of MHC genes2.2.1.3 MHC moleculesProperties of MHC moleculesStructure of MHC molecules2.2.1.4 MHC and peptide interationsProperties of MHC and peptide interationsStructures of MHC-peptide complexClass I MHCClass II MHCImmune functions of MHC and peptide interations2.2.2 Antigen Processing and Presentation to T Lymphocytes2.2.2.1 Antigen presenting cells(APCs)Professional APCsDendritic cellsMacrophagesB lymphocytesnon-professional APCs2.2.2.2 Process of antigen presentationRout of antigen entry, capture and presentation in vivoAntigen capture by APC and present to CD4 Th cellsAntigen presentation to CD8 T cellsCellular pathways of protein antigen processing and presentationMHC II-CD4 Th pathwayantigen uptakeantigen processingMHC II synthesis and antigen loadingsurface expressionMHC I- CD8 CTL pathwayantigen uptakeantigen processingMHC I synthesis antigen loadingsurface expressionPresentation of non-peptide antigens2.2.3 T-cell receptor(TCR) and Accessory Molecules2.2.3.1 T-cell receptor(TCR) complex (recognition and signaling)TCR (αβ /γδ)αβ TCR

γδ TCRSignaling moleculesCD3ζ chain2.2.3.2 T-cell Accessory Molecules (adhesion and signaling)Co-receptors:CD4 and CD8structurefunctionCo-stimulator:CD28 and CTLA-4Signalling molecules:CD45 and CD2adhesion molecules:integrins,selectins and CD442.2.3.3 Other moleculescell markerseffector molecules2.3 B Lymphocytes and Antigen Recognition2.3.1 B-cell receptor(BCR) and Accessory Molecules2.3.1.1 Structure and roles2.3.1.2 BCR complex vs TCR complex2.3.2 Antibodies2.3.2.1 Ig structureChainsIg domainsVarious regionConstant regionHinge region2.3.2.2 Ig classification(Isotypes)2.3.2.3 Ig synthesisGeneral processB cell maturation and Ig modification2.3.2.4 Ig function2.3.3 Antibodies(Ab) and antigen recognition2.3.3.1 Antigens(Ag)Epitope and Ag determinantAntigenicity and immunogenicityProperties of the immunogen contribute to immunogenicityProperties of the immunogenForeignnessMolecular SizeChemical Composition and HeterogeneitySusceptibility to Antigen Processing and PresentationBiological systemGenotype of the Recipient AnimalImmunogen Dosage and Route of AdministrationAdjuvant2.3.3.2 Antigen recognitionThree antigen-recognizing moleculesImmunoglobulin(Ig)T cell receptor(TCR)The Major Histocompatibility Complex (MHC molecules)others

B cell recognition of AntigensCharacteristic properties of B-cell epitopesProperties of antigen and antibody reactionDifferent antibodiesPolyclonal Abs & Monoclonal AbsAnti-Ig Antibodies3. Maturation of B&T lymphocytes3.1 General features of both T and B Lymphocyte maturation3.1.1 Stages of lymphocytes maturation3.1.1.1 Early maturation(produce cell pools)3.1.1.2 Gene recombination(produce antigen receptor repertoires)3.1.1.3 Late maturation(selection of antigen receptor repertoires)3.1.1.4 Functional maturation(produce surface and intracellular effector molecules )3.1.2 Diversity of antigen receptors(BCR/Ig and TCR) 3.1.2.1 Germline organiztion of antigen receptor genes3.1.2.2 Different levels of the generation of diversity3.1.2.3 Mechanisms of the generation of diversityDNA re-arrange(somatic recombination): DNA combinational diversityType of recombinationMechanism of recombinationDNA modification: DNA junctional diversityRNA alternative splicing of constant region3.2 B lymphocytes maturation3.2.1 Stages of B lymphocytes maturation3.2.1.1 Pro-B cell3.2.1.2 Pre-B cell3.2.1.3 Immature B cell3.2.1.4 Mature B cell3.2.2 Types of B cells3.3 T lymphocytes maturation3.3.1 Stages of T lymphocytes maturation3.3.1.1 Pro-T cell3.3.1.2 Early Pre-T cell(double negative)3.3.1.3 Late Pre-T cell(double positive)3.3.1.4 Immature T cell(single positive)3.3.1.5 Mature T cell3.3.2 gd-TCR subset of T lymphocytes4. Activation and Regulation of Lymphocytes (Respond to Antigens)4.1 Activation of T Lymphocytes4.1.1 Biological process (immune responses)4.1.1.1 Initial activationreceptor(TCR) and coreceptor(CD4 and CD-8): recognition of antigen(1st signal)costimulators(2nd signal)4.1.1.2 Immune responsescytokines secretionproliferationdifferentiation4.1.2 Biochemical mechanism (signal transduction)4.1.2.1 Signal reception (across membrane)triggering

clusteringsignal initiation4.1.2.2 Signal amplification (pathway in the cell)Ras-MAP kianse pathwayPLCg-mediated pathways4.1.2.3 Signal destination4.1.3 Signal pathways of T cell activation in the whole map 4.1.3.1 Signaling moleculessignal receptorsChannel-linked receptorG-protein-linked receptorEnzyme linked receptorNon-enzyme linked receptornon-receptor signaling moleculesmembrane proteinreceptor associated membrane proteinsmembrane associate proteinnon-membrane proteins4.1.3.2 Signaling pathwayssignal receptionpassive difussioniron channelG-protein linked signaling transduction systemenzyme-linked signal transduction systemPTK receptorPTK associated recptorCD4/CD8Try phosphatase receptorSer/Thr kinase receptorGuanine cyclase receptorsignal amplificationcascade enzyme amplificationsecond signal linked enzyme amplificationdirectly enter nucleussignal destinationeffector enzymegene expression by transcription factor4.2 Activation of B Lymphocytes4.2.1 Biological process (immune responses)4.2.1.1 Activation by T cell dependent antigens(protein antigen; TD antigen)Initial activation by TD antigens(T cell dependent antigen)Activation by helper T cell (T:B cell interation)antigen-induced migration of B and helper T cellspresentation of protein antigens by B cell to helper T cellsHelper T cell-Mediated activation of B cellsImmune responses (proliferation and differentiation)immune responses induced by TD antigen activation.immune responses induced by helper T activationEarly eventsB cell proliferation

antibody secretion (from membrane Ig to secreting Ig)isotype switchingLate eventsaffinity maturationMemory B cellsPrimary vs. secondary humoral immune response4.2.1.2 Activation by T cell independent antigen (nonprotein antigen;TI antigen)Activation by TI antigenImmune responses induced by IT antigen4.2.1.3 Role of complement in B cell activation4.2.1.4 Factors that influence the amount and type of Ab produced4.2.2 Biological mechanism (signal transduction)4.2.2.1 signal reception(across membrane)triggering of activationinitiation of activation4.2.2.2 signal amplification(pathway in the cell)4.2.2.3 signal destination4.2.3 Antibody responses and feedback5. Effector mechanism of Immune Response (Eliminate Antigens)5.1 Effector function of innate immunity5.1.1 Epithelial barriers5.1.2 Innate immune cells5.1.2.1 PhagocytesNeutrophiles Macrophage5.1.2.2 Dendric cells5.1.2.3 NK cellsOverviewrecognition and activationeffector functionsNK Cell Phenotype and DistributionNK cell recognition of its target cellsNK Cell ReceptorsClassificationBy specificitySummary of MHC I specific receptors:Summary of MHC I non-specific receptorsRelated T cell receptorsBy structure and functionFunctional subsets of natural killer cellsFunctionsMissing Self HypothesisIntegration of Stimulatory and Inhibitory SignalingAdhesion molecules in formation of NK cell–target cell conjugatesThe immunoreceptor tyrosine-based activation motif-dependent activation pathwaysThe DAP10-dependent, ITAM-independent activation pathwayNatural Killer Cell DifferentiationRole of NK cells in diseases Viral InfectionsIntracellular Microbes

Cancer5.1.3 Effector proteins5.1.3.1 Anti-microbial peptides5.1.3.2 Acute phase response proteins (APR proteins)Complement systemFeatures of complement systemPathways of complement activationclassical pathway(activated by antibody)alternative pathwaylectin pathwayEffector function of complement activationcomplement-mediated cytolysiscomlement mediated opsonization and phagocytosisstimulation of inflammatory responsesother functionsRegulation of complement activationregulators of complement activationmechanisms of regulation other APR proteins5.2 Effector function of adaptive immunity5.2.1 Effector function of Cell-mediated immunity(CMI)5.2.1.1 Types of cell-mediated immunityEffector function of NK cellsEffector function CD4 Th1 cellsEffector functions of CD4 Th2 cellsEffector function of CD8 CTLEffector CTLs Are Generated from CTL PrecursorsTwo CTL killing mechanisms5.2.1.2 General properties of effector T cellsThe Activation Requirements of T Cells DifferCell-Adhesion Molecules Facilitate TCR-Mediated InteractionsEffector T Cells Express a Variety of Effector Molecules5.2.1.3 Phases of Cell-mediated immune responsesDevelopment of effector T cells in peripheral lymphoid organsantigen recognition and activationclonal expansiondifferentiationnaive CD4 cells to Subsets of effector cellsNaive CD8 cells to CTLsMigration and retention of leukocytes to infection sitesEffector mechanism of cell-mediated immunity5.2.2 Effector function of Humoral immunity5.2.2.1 General properties of effector functions of antibodies Locations of antibody functioningProduction of antibodyActivation of antibody functionAntibody functions5.2.2.2 Types of effector functions of antibodiesAntibody neutralization of microbe and toxinsAntibody-mediated opsonization and phagocytosis

Antibody-dependent cellular cytotoxicityComplement activation(classical pathway)5.2.2.3 Effector functions of antibodies at special anatomic sitesmucosal immunityneonatal immunity5.3 Connections between innate and adaptive immunitgy6. Regulation of Immune reponses6.1 Cytokines and their receptors6.1.1 Cytokines6.1.1.1 General properties of cytokines6.1.1.2 Classifications of cytokinesAccording to cell resourcesAccording to the functionsBased on their principle biologic actions:Based on their immunological roles:6.1.1.3 Functional categories of cytokinesCytokines that mediate and regulate innate immunityTNFChemokinesType I IFN (a and b)InterleukinIL-1IL-12IL-10othersCytokines that mediate and regulate adaptive immunityInterleukinIL-2IL-4IL-5Type II IFN (g)Growth factorothersCytokines that stimulate hematopoiesisStem cell factorInterleukinIL-7IL-36.1.2 Cytokine receptors6.1.2.1 Classifications of cytokine receptorsIg super familyClass I cytokine receptorsClass II cytokine receptorsTNF receptorsChemokine receptors6.1.2.2 Examples of most studied cytokine receptorsIL-2RIL-15Rmode of reactionThe same cell both produces and transpresents IL-15

Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cellsreceptor shedding6.1.3 Cytokine signaling pathways6.1.3.1 JAK-STAT pathways6.1.3.2 IFN signaling pathway6.1.4 Regulation of cytokine production and functions6.1.4.1 Cytokine Antagonists6.1.4.2 Cytokine Secretion by TH1and TH2 CD4 T cells SubsetsThe Development of TH1 and TH2 Subsets Is Determined by the Cytokine EnvironmentCytokine Profiles Are Cross-Regulated6.1.4.3 Cytokine diseases Diseases caused by Th1/Th2 cytokine imbalanceBacterial Septic or Toxic shock6.1.4.4 cytokine-based therapy6.2 Immunological Memory6.2.1 T cell memory6.2.1.1 CD8 T cell clssification6.2.1.2 T cells memory developmentAntigen persistenceSignals strengthRegulation of genesTime courseOther tid-bits6.2.1.3 T cells memory functions: linking “memory” to “protection6.2.1.4 T cell memory maintenance and longevity6.2.1.5 Effect of heterologous infections on memory6.2.2 B cell memory6.2.2.1 B cells memory and plasma cells developmentanitgen persistenceplasma cell ontogeny6.2.2.2 B memory cell activation6.2.2.3 B cell memory maintenance and longevity6.3 Immunologic tolerance (inactivation of lymphocytes) 6.3.1 General feature and mechanismof immunologic tolerance 6.3.2 Self Tolerance6.3.2.1 Central toleranceCentral T cell tolerancePositive selectionNegative selectionCentral B cell tolerance6.3.2.2 Peripheral tolerancePeripheral T cell toleranceAnergy induced by lack of costimulationinduced by inhibitory receptorsDeletion activation-induced cell death(fas-mediated)"passive cell death (fail to encounter self-antigen)Terminal signaling

Inhibited by Regulatory T cellsPerpheral B cell tolerance6.3.3 Foreign Tolerence6.3.3.1 Factors that determine the tolerogenicity of protein antigens6.3.3.2 Induction and Breaking ToleranceInduction of ToleranceOral toleranceSoluble-peptide toleranceFixed-cell toleranceCo-stimulatory blockadeBreaking Tolerance6.3.4 Homeostasis: termination of normal immune responses6.3.5 Autoimmune Diseases6.3.5.1 Multiple sclerosis(MS)6.3.5.2 R-EAE6.3.5.3 TMEV-IDD6.4 New subsets of CD4 T cells: Regulotary T cells(Tregs) and Th17 effector CD4 T cells6.4.1 Treg6.4.1.1 General properties6.4.1.2 Different regulatory T cellsFoxp3+ Natural Treg(contact)Foxp3+ adaptive Treg(TGFb)Foxp3- adaptive Treg(IL10)6.4.2 Th176.4.2.1 Identification of Th176.4.2.2 Th17 in EAE6.4.2.3 Antagonism of Th177. Inflammation and Leukocytes migration7.1 Inflammation7.1.1 Initiation of inflammation7.1.2 Acute inflammation7.1.2.1 Main features of acute inflammationvasodilationincreased vascular permeabilityleukocytes recruitment and activationfever7.1.2.2 Local and systemic acute inflammationlocal inflammationsystemic inflammation7.1.2.3 Mediators of acute inflammationMolecular mediatorsThe Plasma ProteasesLipid MediatorsPeptides and AminesNitric OxideAcute-Phase ReactantsProinflammatory CytokinesNovel Mediators: Leptin and LipocalinsCell mediatorsNeutrophils

Monocytes and MacrophagesEosinophilsPlatelets and LymphocytesEndothelial and Epithelial Cells7.1.3 Chronic inflammation7.1.3.1 Features of acute inflammation7.1.3.2 Chronic inflammation diseases7.1.4 Anti-Inflammatory Agents7.1.4.1 Antibody Therapies7.1.4.2 Corticosteroids7.1.4.3 NSAIDs7.2 Cell-Adhesion Molecules(CAM)7.2.1 Families of CAM7.2.1.1 SELECTINS7.2.1.2 MUCINS7.2.1.3 INTEGRINS7.2.1.4 ICAMS7.2.2 Functions of CAM7.3 Chemokines—Key Mediators of Inflammation7.3.1 Families of chemokines and chemokine receptors7.3.2 functions and mechanims of chemokines7.4 Leukocytes migration7.4.1 Neutrophil Extravasation7.4.1.1 Step 1: Tethering & rolling7.4.1.2 Steps 2 & 3: Activation & arrestactivationarrest7.4.1.3 Step 4:Migration and diapedesisDiapedisis: pathways of lymphocyte migration across endothelial cellsmigration7.4.2 Lymphocytes Extravasation and Recirculation7.4.2.1 Lymphocyte extravsationHigh-Endothelial Venules and post-capillary venulesAdhesion-Molecule InteractionsHow do lymphocyte move7.4.2.2 Lymphocyte circulationNaive lymphocytes recirculate to secondary lymph node tissueInflammation-induced lymphocyte recirculationinduction of inflammation Innate Signals Are Sufficient to Induce Lymph Node HypertrophyInflammation Induces Recruitment of Nondividing Naive Lymphocytes to the dLNInflammation-Induced Recirculation Occurs via the High Endothelial Venule(HEV)Effector and Memory Lymphocytes Adopt Different Trafficking Patterns(Tissue specificity and imprinting of lymphocyte migration)Tissue-specific DCsSpecific homing phenotype of lymphocytesTissue specific microenvironments determines the homing phenotype of lymphocytesAdoptive cell transfer experimentStromal cell networks7.4.2.3 Regulatory molecules in lymphocyte circulation

Tetinoic acidS1P1(S1P receptor) is necessary for lymphocyte egress from LNmechanism of sequestrating drug FTY270(S1P agonist)S1P1-/- T and B cells fail to accumulate in secondary lymphoid tissueCD69 acts downstream of interferon-a/b to inhibit S1P1 and lymphocyte egress from lymphoid organs8. Mucosal immunology8.1 General properties of the mucosal immune system8.2 Components and structure of mucosal immune system8.2.1 Small intestinal structure8.2.2 Gut associated lymphoid tissues(GALT)8.2.2.1 M cells8.2.2.2 Intraepithelial Lymphocytes (IEL)8.2.2.3 Intestinal epithelial cells (IECs)8.2.2.4 DC8.2.2.5 Lamina propria lymphocytesT cellsB cells and IgA8.3 Antigenic challenge and immune responses in intesitine8.3.1 Antigenic challenge in intestine8.3.2 Immune responses in intesitine8.3.2.1 Commensals vs pathogensCommensals protect epithelial damage via TLR pathwayLimited penetration of commensals insured by mucosal immune systemCommensal loaded DCs can induce IgAPenetration of E. cloacae after intestinal challenge.8.3.2.2 Food tolerance9. Immune Defences9.1 Immunity to Infectious Agents9.1.1 Immunity to Bacteria9.1.1.1 General Aspects of BacterialBacterial adherence and ColonizationPotential Colonization SitesWays of adherenceBacterial virulence factorsBacterial infectionRout of infectionSpread of InfectionExtracellular vs intracellular bacteriaHost primary physical and chemical barrier defense9.1.1.2 Extracellular bacteriaImmunity against extracellular bacteriainnate immune responseadaptive responseInvade mechanisms by extracellular bacteriaAvoiding phagocytosisToxinsDelivery of toxinsEffect of toxinToxic shock syndrome

Toxicity of LPSExample of extracellular bacteria:Helicobacter pyloriH. pylori Virulence FactorsVacACagAHp LPS – Immune MimicryPeptidoglycan (PGN)immune response to H.pylori9.1.1.3 Intracellular bacteriaImmunity against intracellular bacteriahumoral responsecell mediated responseinnate cell-mediated responseadaptive cell-mediated responseInvasion mechanism of intracellular bacteriaPhagocytosisclatherin-independent“Zippering” method of internalizationRuffling method of internalizationM cell InternalizationSurvival Strategies within PhagocytesExample of intracellular bacteria: salmonella9.1.1.4 Diseases and pathogenesis by bacteriaDamage from immune responseDiphtheria (Corynebacterium diphtheriae)Tuberculosis (Mycobacterium tuberculosis)9.1.2 Immunity to Virus9.1.2.1 Host immune response to virusinnate immune responseadaptive immune response9.1.2.2 Mechanisms of immune evasion by virusEscape by MutationsEscape by HidingEscape by LatencyEscape by Destruction of Immune CellsEscape by Subverting Antigen Processing and Antigen PresentationInhibition of T Cell-Mediated Target Cell LysisInhibition of Natural Killer Cell ActivityInhibition of Complement ActivationInterference of Cytokine FunctionsCrystallized Fragment (Fc) Receptor Mimetics9.1.3 Immunity to Parasites9.1.3.1 Nature of parasitic pathogens9.1.3.2 Host Immune responses to parasitesinnate immune responseadaptive immune response9.1.3.3 Mechanism of immune evasion by parasites9.1.3.4 Anti-malarial immunity and pregnancyMalaria biologyIntroduction

Life cycleMalaria during pregnancyPathogenesis of malariaPlacental CytoadherenceAntigen VariationImmunogenesis of malariaT cell responsesHumoral responses9.2 Immunity to Transplantation 9.2.1 Immunologic Basis of Graft Rejection9.2.1.1 Types of transplants and graft rejection9.2.1.2 Properties of graft rejectionAllograft Rejection Displays Specificity and MemorySimilar Antigenic Profiles Foster Allograft AcceptanceCell-Mediated Graft Rejection Occurs in Two StagesGraft Donors and Recipients Are Typed for RBC and MHC Antigens9.2.2 Immune response to allogenenic transplantation9.2.2.1 Alloantigens presentation by recognition of T cellsdirect presentation of alloantigensindirect presentation of alloantigens9.2.2.2 Activation of alloreactive T cells CD4 /CD8 T cell activation in vivomixed lymphocyte reaction(MLR)9.2.2.3 Effector mechanisms of allograft rejection9.2.3 Clinical Manifestations of Graft Rejection 9.2.3.1 Hyperacute rejection9.2.3.2 Acute rejection9.2.3.3 Chronic rejection9.3 Immunity to tumors9.3.1 Cancer: Origin and Terminology9.3.1.1 Origin of Cancer9.3.1.2 Cancer associated genes9.3.1.3 Cancer induction process9.3.2 Tumor immunology9.3.2.1 Tumor antigensIdentification of tumor antigensTwo types of tumor antigensTumor-specific transplantation antigens(TSTAs)products of mutated oncogenes and tumor suppressor genesproducts of other mutated genestumor antigens encoded by genomes of oncogenic virusesTumor-associated transplantation antigens(TATAs)overexpressed and abnormally expressed cellular proteinsaltered glycolipid and glycoprotein antigensTissue-specific differentiation antigensoncofetal antigens9.3.2.2 Immune response to tumorsNK cellsmacrophagesT cells

antibodies9.3.3 Tumor Evasion of immune response10. Immune Diseases 10.1 Hypersensitivity and Autoimmune diseases(Abnormal immune responses) 10.1.1 Effector mechanisms of abnormal immune responses and diseases10.1.1.1 Antibody mediatedAntibody-mediatedAntibody-antigen complex mediated10.1.1.2 T cells mediated10.1.2 Hypersensitivity diseases10.1.2.1 Causes of hypersensitivity10.1.2.2 Types of hypersensitivityType I: IgE antibody mediated Immediate Hypersensitivity (uncontrolled or excessive responses against foreign antigens)Components of type I hypersensitivityAllergensREAGINIC ANTIBODY (IgE)Mast cells, basophils and eosinophileIgE-BINDING Fc RECEPTORSSequence of eventsProduction of IgEBinding of IgE to IgE Fc receptor on Mast cells and BasophilesActivation of effector cellsActivation of Mast cellsMediators produced by effector cellsRegulation of mast cell degranuationBiological effectTwo effector phases of type I hypersensivity reactionsEarly phase reaction(immediate)Late phase reactions(2-4hours)Detect Type I Hypersensitivity ReactionsType I hypersensitivity diseases and therapiesSystemic/loclized anaphylaxisSYSTEMIC ANAPHYLAXISLOCALIZED ANAPHYLAXIS (ATOPY)ALLERGIC RHINITISBronchial AsthmaAllergies of skin, upper respiratory and gutTherapiesimmunotherapytherapeutic drugsPathogenesis of type I hypersensitivityGenetic susceptibilityHygene hypothesisType II: IgG antibody mediated Cytotoxic Hypersensitivity (immune antibody response against self-antigen) Blood Transfusion ReactionsHemolytic Disease of the NewbornDrug-Induced Hemolytic Anemia

Type III: Antibody-antigen complex mediated Hypersensitivity (self antigens or foreign antigens with bound antibody)Type IV: T cell mediated Hypersensitivity(Delayed type hypersensitivity, DTH): autoimmune response or response to foreign antigens Effector functionsPhases of reactionDetectionDiseases10.1.3 Autoimmune diseases10.1.3.1 General properties of autoimmune disease10.1.3.2 Types of autoimmune diseasesOrgan specific autoimmune diseasesMediated by Direct Cellular DamageMediated by Stimulating or Blocking Auto-AntibodiesSystemic autoimmune diseases10.1.3.3 Proposed mechanism for induction of autommune diseasesGenetic basis of autoimmune diseaseRole of infections in autoimunityRelease of Sequestered Antigens Can Induce Autoimmune DiseaseInappropriate Expression of Class II MHC Molecules Can Sensitize Autoreactive T CellsPolyclonal B-Cell Activation Can Lead to Autoimmune Disease10.2 Congenital and acquired immunodeficiencies (Lack of immune responses)10.2.1 Congenital(Primary) immunodeficiencies10.2.1.1 Defects in innate immunitydefect in microbicidal activities of phagocytesleukocyte adhesion deficienciesdefect in NK cells and other leukocytes: the Chediak-Higashi syndrom10.2.1.2 Defects in adaptive immunityDefects in lymphocytes maturationdisorder of both B and T cells(severe combined immunodeficiencies, SCIDs)X-linked SCID caused by mutation of the cytokine receptor commom g chainSCID caused by Adenosine deaminase deficiencydefect in B cell maturation: X-linked agammaglobulinemiadefect in T cell maturation: DiGeorge syndromeDefects in lymphocytes activation and functiondefect in B cell activation and functionselective immunoglobulin isotype deficienciesdefects in B cell differentiation: common variable immunodeficiencydefect in T cell activation and functionDefect in T cell-dependent B cell activation: the X-linked hype-IgM syndromdefects in T cell activation and functionDefects in MHC expression10.2.2 Acquired(Secondary) immunodeficiencies10.2.2.1 Pathogenic mechanisms10.2.2.2 HIV and the Acquired Immunodeficiency Syndrome(AIDS)Molecular and biologic features of HIVHIV structure and GenesViral life cycleentryreplication and regulation

packageThe course of HIV diseaseHIV infectionSteps in HIV infection and pathogenesisHIV reservoirs and viral turnoverimmune responses to HIVmechanism of immunodeficiencyimmune evasion by HIVTreatment and prevention of AIDS11. Immunotherapy: Manipulation of immune responses11.1 Activation of immune respones11.1.1 Vaccination against infectious agents11.1.1.1 IntroductionHistory of vaccineTerminology of vaccinationVaccine ClassificationsVaccines of two different strategies Three basic vaccinesOther vaccines11.1.1.2 Passive and active immunizationPassive immunizationCommon agents of passive immunizationConditions that warrant the use of passive immunizationAdvantage and disadvantageActive immunizationNatrual infectionVaccination programsVaccines for use in humans to dateVaccines used in National Immunization Programs11.1.1.3 Requirements for effective vaccinationVaccine typesWhole organism vaccineLive attenuated vaccineInactivated vaccineSubunit vaccineDNA vaccineRecombinant viral vector DNA vaccineRecombinant plasmid DNA vaccinePeptide vaccineimmunogenic peptide identificationproblems and overcomesTI antigen and conjugate vaccineAdjuvantmicrobial constituentsComplete Freund's Adjuvant(CFA)Bacterial toxins(CT,LT) and derivativesCpG containing DNACytokines/chemokinesLive vectorsvirus like particles

adjuvant as particulate delivery systemsmicorspheresliposomeslipopeptidessingle chain lipidclustered lipid chainLipid core peptide(LCP) systemRout of vaccination11.1.1.4 Designing of therapeutic vaccine to control existing chronic infectionsTwo cases of chronic infectionsTreatment of chronic infections11.1.2 Tumor immunotherapy11.1.2.1 Active immunotherapyvaccination with tumor cells and tumor antigensaugmentation of host immunity to tumors by using cytokines and costimulators transfected tumor cellsnonspecific stimualtion of the immune system11.1.2.2 Passive immunotherapyTherapy with anti-tumor antibodiesAdoptive cellular therapy11.2 Suppression of immune responses11.2.1 Immune tolerance or supression of allograft transplatation11.2.1.1 Immunosupression therapy of allograft rejectionGeneral immunosuppressive therapyImmunosuppression of T cellsplasmaphoresisanti-inflammatory agentsMitotic InhibitorsTotal Lymphoid Irradiation EliminatesLymphocytesSpecific immunosuppressive therapyMonoclonal Antibodies Can Suppress Graft-Rejection ResponsesBlocking Co-Stimulatory Signals to Induce Anergy11.2.1.2 Immune tolerance to allograft11.2.2 Immunotherapy of hypersensitivity11.2.3 Immunotherapy of autoimmune diseases11.2.3.1 T-Cell Vaccination Is a Possible Therapy11.2.3.2 Some experimental agents for immunointervention11.2.3.3 Oral Antigens Can Induce Tolerance

Immunolgy

1.1.1 Overview of immune responses in vivo

1.1.2 Classification 1.1.2.1 innate and adaptive immunity

Innate immune response stimulates adaptive immune responses. Adaptive immune enhances innate immunity.They are components of an integrated system of host defense system.

Innate immunity also called natural or native immunity: cellular and biochemical defense mechanisms that are in place before infection and respond rapidly to infections.Components:

physical and cheical barriers:skin, mucosal epithelia,antimicrobial chemicals blood proteins: complement cells: phagocytes

adaptive immunity stimulated by exposure to infectious agents and increase in magnitude and defensive capabilities with each successive exposure to a particular antigens.features Specificity and Memory :mount heightened response to persist infection of the same

antigen.

A substantial specific response takes TIME & ENERGY.

Diversity: Respond in distinct and special ways to different micobes which enables the host to "custom design" responses to best combat many different types of microbes.

specialization: Respond in distinct and special ways to different micobes which enables the host to "custom design" responses to best combat many different types of microbes.

self-limitation: Return to resting basal state, called homeostatsis, after antigen stimulation

self-nonreactivity: also called self-tolerance. prevent to react against one's own cells.

phases 5 phases:

recognition of antigen activation of lymphocytes antigen elimination (effector phase) homeostasis memory

1.1.2.2 humoral and cell-mediated immunity

humoral immunity

mediated by molecules in the blood and mucosal secretions.called antibodies,that are produced by B cells.

principal defense against extracellular microbes

cell-mediated immunity mediated by T lymphocytes. principal defense against intracellular microbes.

1.1.2.3 active and passive immunity active immunity: protective immunity induced by exposure to a foreign antigen. passive immunity:protective immunity gained by tranfering antibodies or lymphocytes

specific for an antigen without ever having been exposed to or having respond to that antigens.