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  1. 1. HYPERLINK "" l "Topic2" 1. Introduction to Immunology<br />1.1 General Properties of Immune Responses<br />1.1.1 Overview of immune responses in vivo<br />1.1.2 Classification<br /> innate and adaptive immunity<br />Innate immunity<br />adaptive immunity<br />features<br />phases<br /> humoral and cell-mediated immunity<br />humoral immunity<br />cell-mediated immunity<br /> active and passive immunity<br />1.2 Components of Immune Systems<br />1.2.1 Tissues and organs of immune systems<br /> generative organs (primary lymphoid organs)<br />Bone Marrow<br />Thymus<br /> peripheral organs (secondary lymphoid organs)<br />lymph nodes<br />spleen<br />cutaneous immune system<br />mucosal immune system<br />1.2.2 Cells of immune systems<br /> lymphoid progenitor cells <br />B lymphocytes<br />T lymphocytes<br />NK cells<br />NKT cells<br /> myeloid progenitor cells<br />Granulocytes<br />Mast cells<br />Macrophages(Mononuclear phagocytes )<br /> Dendritic cells(DC)<br />2. Recognition of Antigens<br />2.1 Innate immune cells and anitgen recognition<br />2.1.1 Pathogen associated molecular patterns(PAMPs)<br />2.1.2 Pattern recognition recptors(PRRs) and signaling pathways<br /> PPRs<br />Membrane-bound PPRs<br />mannose receptor<br />Scavenger receptor<br />Toll-like receptor(TLR)<br />Cytoplasmic PRRs<br />NOD Like Receptors<br />RIG-I-like RNA helicase(RLH)<br /> PRR(TLR/RLH) signalling pathway<br />TLR signaling pathway<br />Adaptor molecules in the pathway<br />two basic pathways<br />RLH signaling pathway<br />2.1.3 PAMPs and PRRs interations during viral infections<br /> TLR/RLH recognition of viral infection<br />Vial recognition by TLRs<br />Viral recognition by RLHs<br /> Viral antagonist of PRR signalling pathways<br /> The therapeutic application of manipulation of PRR signalling pathways<br />2.2 T Lymphocytes and Antigen Recognition<br />2.2.1 The Major Histocompatibility Complex (MHC molecules)<br /> Discovery of MHC<br /> MHC genes<br />Properties of MHC genes<br />Genomic organiztion of MHC<br />Expression and regualtion of MHC genes<br /> MHC molecules<br />Properties of MHC molecules<br />Structure of MHC molecules<br /> MHC and peptide interations<br />Properties of MHC and peptide interations<br />Structures of MHC-peptide complex<br />Class I MHC<br />Class II MHC<br />Immune functions of MHC and peptide interations<br />2.2.2 Antigen Processing and Presentation to T Lymphocytes<br /> Antigen presenting cells(APCs)<br />Professional APCs<br />Dendritic cells<br />Macrophages<br />B lymphocytes<br />non-professional APCs<br /> Process of antigen presentation<br />Rout of antigen entry, capture and presentation in vivo<br />Antigen capture by APC and present to CD4 Th cells<br />Antigen presentation to CD8 T cells<br />Cellular pathways of protein antigen processing and presentation<br />MHC II-CD4 Th pathway<br />antigen uptake<br />antigen processing<br />MHC II synthesis and antigen loading<br />surface expression<br />MHC I- CD8 CTL pathway<br />antigen uptake<br />antigen processing<br />MHC I synthesis antigen loading<br />surface expression<br />Presentation of non-peptide antigens<br />2.2.3 T-cell receptor(TCR) and Accessory Molecules<br /> T-cell receptor(TCR) complex (recognition and signaling)<br />TCR (αβ /γδ)<br />αβ TCR<br />γδ TCR<br />Signaling molecules<br />CD3<br />ζ chain<br /> T-cell Accessory Molecules (adhesion and signaling)<br />Co-receptors:CD4 and CD8<br />structure<br />function<br />Co-stimulator:CD28 and CTLA-4<br />Signalling molecules:CD45 and CD2<br />adhesion molecules:integrins,selectins and CD44<br /> Other molecules<br />cell markers<br />effector molecules<br />2.3 B Lymphocytes and Antigen Recognition<br />2.3.1 B-cell receptor(BCR) and Accessory Molecules<br /> Structure and roles<br /> BCR complex vs TCR complex<br />2.3.2 Antibodies<br /> Ig structure<br />Chains<br />Ig domains<br />Various region<br />Constant region<br />Hinge region<br /> Ig classification(Isotypes)<br /> Ig synthesis<br />General process<br />B cell maturation and Ig modification<br /> Ig function<br />2.3.3 Antibodies(Ab) and antigen recognition<br /> Antigens(Ag)<br />Epitope and Ag determinant<br />Antigenicity and immunogenicity<br />Properties of the immunogen contribute to immunogenicity<br />Properties of the immunogen<br />Foreignness<br />Molecular Size<br />Chemical Composition and Heterogeneity<br />Susceptibility to Antigen Processing and Presentation<br />Biological system<br />Genotype of the Recipient Animal<br />Immunogen Dosage and Route of Administration<br />Adjuvant<br /> Antigen recognition<br />Three antigen-recognizing molecules<br />Immunoglobulin(Ig)<br />T cell receptor(TCR)<br />The Major Histocompatibility Complex (MHC molecules)<br />others<br />B cell recognition of Antigens<br />Characteristic properties of B-cell epitopes<br />Properties of antigen and antibody reaction<br />Different antibodies<br />Polyclonal Abs & Monoclonal Abs<br />Anti-Ig Antibodies<br />3. Maturation of B&T lymphocytes<br />3.1 General features of both T and B Lymphocyte maturation<br />3.1.1 Stages of lymphocytes maturation<br /> Early maturation(produce cell pools)<br /> Gene recombination(produce antigen receptor repertoires)<br /> Late maturation(selection of antigen receptor repertoires)<br /> Functional maturation(produce surface and intracellular effector molecules )<br />3.1.2 Diversity of antigen receptors(BCR/Ig and TCR) <br /> Germline organiztion of antigen receptor genes<br /> Different levels of the generation of diversity<br /> Mechanisms of the generation of diversity<br />DNA re-arrange(somatic recombination): DNA combinational diversity<br />Type of recombination<br />Mechanism of recombination<br />DNA modification: DNA junctional diversity<br />RNA alternative splicing of constant region<br />3.2 B lymphocytes maturation<br />3.2.1 Stages of B lymphocytes maturation<br /> Pro-B cell<br /> Pre-B cell<br /> Immature B cell<br /> Mature B cell<br />3.2.2 Types of B cells<br />3.3 T lymphocytes maturation<br />3.3.1 Stages of T lymphocytes maturation<br /> Pro-T cell<br /> Early Pre-T cell(double negative)<br /> Late Pre-T cell(double positive)<br /> Immature T cell(single positive)<br /> Mature T cell<br />3.3.2 gd-TCR subset of T lymphocytes<br />4. Activation and Regulation of Lymphocytes (Respond to Antigens)<br />4.1 Activation of T Lymphocytes<br />4.1.1 Biological process (immune responses)<br /> Initial activation<br />receptor(TCR) and coreceptor(CD4 and CD-8): recognition of antigen(1st signal)<br />costimulators(2nd signal)<br /> Immune responses<br />cytokines secretion<br />proliferation<br />differentiation<br />4.1.2 Biochemical mechanism (signal transduction)<br /> Signal reception (across membrane)<br />triggering<br />clustering<br />signal initiation<br /> Signal amplification (pathway in the cell)<br />Ras-MAP kianse pathway<br />PLCg-mediated pathways<br /> Signal destination<br />4.1.3 Signal pathways of T cell activation in the whole map <br /> Signaling molecules<br />signal receptors<br />Channel-linked receptor<br />G-protein-linked receptor<br />Enzyme linked receptor<br />Non-enzyme linked receptor<br />non-receptor signaling molecules<br />membrane protein<br />receptor associated membrane proteins<br />membrane associate protein<br />non-membrane proteins<br /> Signaling pathways<br />signal reception<br />passive difussion<br />iron channel<br />G-protein linked signaling transduction system<br />enzyme-linked signal transduction system<br />PTK receptor<br />PTK associated recptor<br />CD4/CD8<br />Try phosphatase receptor<br />Ser/Thr kinase receptor<br />Guanine cyclase receptor<br />signal amplification<br />cascade enzyme amplification<br />second signal linked enzyme amplification<br />directly enter nucleus<br />signal destination<br />effector enzyme<br />gene expression by transcription factor<br />4.2 Activation of B Lymphocytes<br />4.2.1 Biological process (immune responses)<br /> Activation by T cell dependent antigens(protein antigen; TD antigen)<br />Initial activation by TD antigens(T cell dependent antigen)<br />Activation by helper T cell (T:B cell interation)<br />antigen-induced migration of B and helper T cells<br />presentation of protein antigens by B cell to helper T cells<br />Helper T cell-Mediated activation of B cells<br />Immune responses (proliferation and differentiation)<br />immune responses induced by TD antigen activation.<br />immune responses induced by helper T activation<br />Early events<br />B cell proliferation<br />antibody secretion (from membrane Ig to secreting Ig)<br />isotype switching<br />Late events<br />affinity maturation<br />Memory B cells<br />Primary vs. secondary humoral immune response<br /> Activation by T cell independent antigen (nonprotein antigen;TI antigen)<br />Activation by TI antigen<br />Immune responses induced by IT antigen<br /> Role of complement in B cell activation<br /> Factors that influence the amount and type of Ab produced<br />4.2.2 Biological mechanism (signal transduction)<br /> signal reception(across membrane)<br />triggering of activation<br />initiation of activation<br /> signal amplification(pathway in the cell)<br /> signal destination<br />4.2.3 Antibody responses and feedback<br />5. Effector mechanism of Immune Response (Eliminate Antigens)<br />5.1 Effector function of innate immunity<br />5.1.1 Epithelial barriers<br />5.1.2 Innate immune cells<br /> Phagocytes<br />Neutrophiles <br />Macrophage<br /> Dendric cells<br /> NK cells<br />Overview<br />recognition and activation<br />effector functions<br />NK Cell Phenotype and Distribution<br />NK cell recognition of its target cells<br />NK Cell Receptors<br />Classification<br />By specificity<br />Summary of MHC I specific receptors:<br />Summary of MHC I non-specific receptors<br />Related T cell receptors<br />By structure and function<br />Functional subsets of natural killer cells<br />Functions<br />Missing Self Hypothesis<br />Integration of Stimulatory and Inhibitory Signaling<br />Adhesion molecules in formation of NK cell–target cell conjugates<br />The immunoreceptor tyrosine-based activation motif-dependent activation pathways<br />The DAP10-dependent, ITAM-independent activation pathway<br />Natural Killer Cell Differentiation<br />Role of NK cells in diseases <br />Viral Infections<br />Intracellular Microbes<br />Cancer<br />5.1.3 Effector proteins<br /> Anti-microbial peptides<br /> Acute phase response proteins (APR proteins)<br />Complement system<br />Features of complement system<br />Pathways of complement activation<br />classical pathway(activated by antibody)<br />alternative pathway<br />lectin pathway<br />Effector function of complement activation<br />complement-mediated cytolysis<br />comlement mediated opsonization and phagocytosis<br />stimulation of inflammatory responses<br />other functions<br />Regulation of complement activation<br />regulators of complement activation<br />mechanisms of regulation <br />other APR proteins<br />5.2 Effector function of adaptive immunity<br />5.2.1 Effector function of Cell-mediated immunity(CMI)<br /> Types of cell-mediated immunity<br />Effector function of NK cells<br />Effector function CD4 Th1 cells<br />Effector functions of CD4 Th2 cells<br />Effector function of CD8 CTL<br />Effector CTLs Are Generated from CTL Precursors<br />Two CTL killing mechanisms<br /> General properties of effector T cells<br />The Activation Requirements of T Cells Differ<br />Cell-Adhesion Molecules Facilitate TCR-Mediated Interactions<br />Effector T Cells Express a Variety of Effector Molecules<br /> Phases of Cell-mediated immune responses<br />Development of effector T cells in peripheral lymphoid organs<br />antigen recognition and activation<br />clonal expansion<br />differentiation<br />naive CD4 cells to Subsets of effector cells<br />Naive CD8 cells to CTLs<br />Migration and retention of leukocytes to infection sites<br />Effector mechanism of cell-mediated immunity<br />5.2.2 Effector function of Humoral immunity<br /> General properties of effector functions of antibodies <br />Locations of antibody functioning<br />Production of antibody<br />Activation of antibody function<br />Antibody functions<br /> Types of effector functions of antibodies<br />Antibody neutralization of microbe and toxins<br />Antibody-mediated opsonization and phagocytosis<br />Antibody-dependent cellular cytotoxicity<br />Complement activation(classical pathway)<br /> Effector functions of antibodies at special anatomic sites<br />mucosal immunity<br />neonatal immunity<br />5.3 Connections between innate and adaptive immunitgy<br />6. Regulation of Immune reponses<br />6.1 Cytokines and their receptors<br />6.1.1 Cytokines<br /> General properties of cytokines<br /> Classifications of cytokines<br />According to cell resources<br />According to the functions<br />Based on their principle biologic actions:<br />Based on their immunological roles:<br /> Functional categories of cytokines<br />Cytokines that mediate and regulate innate immunity<br />TNF<br />Chemokines<br />Type I IFN (a and b)<br />Interleukin<br />IL-1<br />IL-12<br />IL-10<br />others<br />Cytokines that mediate and regulate adaptive immunity<br />Interleukin<br />IL-2<br />IL-4<br />IL-5<br />Type II IFN (g)<br />Growth factor<br />others<br />Cytokines that stimulate hematopoiesis<br />Stem cell factor<br />Interleukin<br />IL-7<br />IL-3<br />6.1.2 Cytokine receptors<br /> Classifications of cytokine receptors<br />Ig super family<br />Class I cytokine receptors<br />Class II cytokine receptors<br />TNF receptors<br />Chemokine receptors<br /> Examples of most studied cytokine receptors<br />IL-2R<br />IL-15R<br />mode of reaction<br />The same cell both produces and transpresents IL-15<br />Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells<br />receptor shedding<br />6.1.3 Cytokine signaling pathways<br /> JAK-STAT pathways<br /> IFN signaling pathway<br />6.1.4 Regulation of cytokine production and functions<br /> Cytokine Antagonists<br /> Cytokine Secretion by TH1and TH2 CD4 T cells Subsets<br />The Development of TH1 and TH2 Subsets Is Determined by the Cytokine Environment<br />Cytokine Profiles Are Cross-Regulated<br /> Cytokine diseases <br />Diseases caused by Th1/Th2 cytokine imbalance<br />Bacterial Septic or Toxic shock<br /> cytokine-based therapy<br />6.2 Immunological Memory<br />6.2.1 T cell memory<br /> CD8 T cell clssification<br /> T cells memory development<br />Antigen persistence<br />Signals strength<br />Regulation of genes<br />Time course<br />Other tid-bits<br /> T cells memory functions: linking “memory” to “protection<br /> T cell memory maintenance and longevity<br /> Effect of heterologous infections on memory<br />6.2.2 B cell memory<br /> B cells memory and plasma cells development<br />anitgen persistence<br />plasma cell ontogeny<br /> B memory cell activation<br /> B cell memory maintenance and longevity<br />6.3 Immunologic tolerance (inactivation of lymphocytes) <br />6.3.1 General feature and mechanismof immunologic tolerance <br />6.3.2 Self Tolerance<br /> Central tolerance<br />Central T cell tolerance<br />Positive selection<br />Negative selection<br />Central B cell tolerance<br /> Peripheral tolerance<br />Peripheral T cell tolerance<br />Anergy <br />induced by lack of costimulation<br />induced by inhibitory receptors<br />Deletion <br />activation-induced cell death(fas-mediated)<br />"passive cell death (fail to encounter self-antigen)<br />Terminal signaling<br />Inhibited by Regulatory T cells<br />Perpheral B cell tolerance<br />6.3.3 Foreign Tolerence<br /> Factors that determine the tolerogenicity of protein antigens<br /> Induction and Breaking Tolerance<br />Induction of Tolerance<br />Oral tolerance<br />Soluble-peptide tolerance<br />Fixed-cell tolerance<br />Co-stimulatory blockade<br />Breaking Tolerance<br />6.3.4 Homeostasis: termination of normal immune responses<br />6.3.5 Autoimmune Diseases<br /> Multiple sclerosis(MS)<br /> R-EAE<br /> TMEV-IDD<br />6.4 New subsets of CD4 T cells: Regulotary T cells(Tregs) and Th17 effector CD4 T cells<br />6.4.1 Treg<br /> General properties<br /> Different regulatory T cells<br />Foxp3+ Natural Treg(contact)<br />Foxp3+ adaptive Treg(TGFb)<br />Foxp3- adaptive Treg(IL10)<br />6.4.2 Th17<br /> Identification of Th17<br /> Th17 in EAE<br /> Antagonism of Th17<br />7. Inflammation and Leukocytes migration<br />7.1 Inflammation<br />7.1.1 Initiation of inflammation<br />7.1.2 Acute inflammation<br /> Main features of acute inflammation<br />vasodilation<br />increased vascular permeability<br />leukocytes recruitment and activation<br />fever<br /> Local and systemic acute inflammation<br />local inflammation<br />systemic inflammation<br /> Mediators of acute inflammation<br />Molecular mediators<br />The Plasma Proteases<br />Lipid Mediators<br />Peptides and Amines<br />Nitric Oxide<br />Acute-Phase Reactants<br />Proinflammatory Cytokines<br />Novel Mediators: Leptin and Lipocalins<br />Cell mediators<br />Neutrophils<br />Monocytes and Macrophages<br />Eosinophils<br />Platelets and Lymphocytes<br />Endothelial and Epithelial Cells<br />7.1.3 Chronic inflammation<br /> Features of acute inflammation<br /> Chronic inflammation diseases<br />7.1.4 Anti-Inflammatory Agents<br /> Antibody Therapies<br /> Corticosteroids<br /> NSAIDs<br />7.2 Cell-Adhesion Molecules(CAM)<br />7.2.1 Families of CAM<br /> SELECTINS<br /> MUCINS<br /> INTEGRINS<br /> ICAMS<br />7.2.2 Functions of CAM<br />7.3 Chemokines—Key Mediators of Inflammation<br />7.3.1 Families of chemokines and chemokine receptors<br />7.3.2 functions and mechanims of chemokines<br />7.4 Leukocytes migration<br />7.4.1 Neutrophil Extravasation<br /> Step 1: Tethering & rolling<br /> Steps 2 & 3: Activation & arrest<br />activation<br />arrest<br /> Step 4:Migration and diapedesis<br />Diapedisis: pathways of lymphocyte migration across endothelial cells<br />migration<br />7.4.2 Lymphocytes Extravasation and Recirculation<br /> Lymphocyte extravsation<br />High-Endothelial Venules and post-capillary venules<br />Adhesion-Molecule Interactions<br />How do lymphocyte move<br /> Lymphocyte circulation<br />Naive lymphocytes recirculate to secondary lymph node tissue<br />Inflammation-induced lymphocyte recirculation<br />induction of inflammation <br />Innate Signals Are Sufficient to Induce Lymph Node Hypertrophy<br />Inflammation Induces Recruitment of Nondividing Naive Lymphocytes to the dLN<br />Inflammation-Induced Recirculation Occurs via the High Endothelial Venule(HEV)<br />Effector and Memory Lymphocytes Adopt Different Trafficking Patterns(Tissue specificity and imprinting of lymphocyte migration)<br />Tissue-specific DCs<br />Specific homing phenotype of lymphocytes<br />Tissue specific microenvironments determines the homing phenotype of lymphocytes<br />Adoptive cell transfer experiment<br />Stromal cell networks<br /> Regulatory molecules in lymphocyte circulation<br />Tetinoic acid<br />S1P1(S1P receptor) is necessary for lymphocyte egress from LN<br />mechanism of sequestrating drug FTY270(S1P agonist)<br />S1P1-/- T and B cells fail to accumulate in secondary lymphoid tissue<br />CD69 acts downstream of interferon-a/b to inhibit S1P1 and lymphocyte egress from lymphoid organs<br />8. Mucosal immunology<br />8.1 General properties of the mucosal immune system<br />8.2 Components and structure of mucosal immune system<br />8.2.1 Small intestinal structure<br />8.2.2 Gut associated lymphoid tissues(GALT)<br /> M cells<br /> Intraepithelial Lymphocytes (IEL)<br /> Intestinal epithelial cells (IECs)<br /> DC<br /> Lamina propria lymphocytes<br />T cells<br />B cells and IgA<br />8.3 Antigenic challenge and immune responses in intesitine<br />8.3.1 Antigenic challenge in intestine<br />8.3.2 Immune responses in intesitine<br /> Commensals vs pathogens<br />Commensals protect epithelial damage via TLR pathway<br />Limited penetration of commensals insured by mucosal immune system<br />Commensal loaded DCs can induce IgA<br />Penetration of E. cloacae after intestinal challenge.<br /> Food tolerance<br />9. Immune Defences<br />9.1 Immunity to Infectious Agents<br />9.1.1 Immunity to Bacteria<br /> General Aspects of Bacterial<br />Bacterial adherence and Colonization<br />Potential Colonization Sites<br />Ways of adherence<br />Bacterial virulence factors<br />Bacterial infection<br />Rout of infection<br />Spread of Infection<br />Extracellular vs intracellular bacteria<br />Host primary physical and chemical barrier defense<br /> Extracellular bacteria<br />Immunity against extracellular bacteria<br />innate immune response<br />adaptive response<br />Invade mechanisms by extracellular bacteria<br />Avoiding phagocytosis<br />Toxins<br />Delivery of toxins<br />Effect of toxin<br />Toxic shock syndrome<br />Toxicity of LPS<br />Example of extracellular bacteria:Helicobacter pylori<br />H. pylori Virulence Factors<br />VacA<br />CagA<br />Hp LPS – Immune Mimicry<br />Peptidoglycan (PGN)<br />immune response to H.pylori<br /> Intracellular bacteria<br />Immunity against intracellular bacteria<br />humoral response<br />cell mediated response<br />innate cell-mediated response<br />adaptive cell-mediated response<br />Invasion mechanism of intracellular bacteria<br />Phagocytosis<br />clatherin-independent<br />“Zippering” method of internalization<br />Ruffling method of internalization<br />M cell Internalization<br />Survival Strategies within Phagocytes<br />Example of intracellular bacteria: salmonella<br /> Diseases and pathogenesis by bacteria<br />Damage from immune response<br />Diphtheria (Corynebacterium diphtheriae)<br />Tuberculosis (Mycobacterium tuberculosis)<br />9.1.2 Immunity to Virus<br /> Host immune response to virus<br />innate immune response<br />adaptive immune response<br /> Mechanisms of immune evasion by virus<br />Escape by Mutations<br />Escape by Hiding<br />Escape by Latency<br />Escape by Destruction of Immune Cells<br />Escape by Subverting Antigen Processing and Antigen Presentation<br />Inhibition of T Cell-Mediated Target Cell Lysis<br />Inhibition of Natural Killer Cell Activity<br />Inhibition of Complement Activation<br />Interference of Cytokine Functions<br />Crystallized Fragment (Fc) Receptor Mimetics<br />9.1.3 Immunity to Parasites<br /> Nature of parasitic pathogens<br /> Host Immune responses to parasites<br />innate immune response<br />adaptive immune response<br /> Mechanism of immune evasion by parasites<br /> Anti-malarial immunity and pregnancy<br />Malaria biology<br />Introduction<br />Life cycle<br />Malaria during pregnancy<br />Pathogenesis of malaria<br />Placental Cytoadherence<br />Antigen Variation<br />Immunogenesis of malaria<br />T cell responses<br />Humoral responses<br />9.2 Immunity to Transplantation <br />9.2.1 Immunologic Basis of Graft Rejection<br /> Types of transplants and graft rejection<br /> Properties of graft rejection<br />Allograft Rejection Displays Specificity and Memory<br />Similar Antigenic Profiles Foster Allograft Acceptance<br />Cell-Mediated Graft Rejection Occurs in Two Stages<br />Graft Donors and Recipients Are Typed for RBC and MHC Antigens<br />9.2.2 Immune response to allogenenic transplantation<br /> Alloantigens presentation by recognition of T cells<br />direct presentation of alloantigens<br />indirect presentation of alloantigens<br /> Activation of alloreactive T cells <br />CD4 /CD8 T cell activation in vivo<br />mixed lymphocyte reaction(MLR)<br /> Effector mechanisms of allograft rejection<br />9.2.3 Clinical Manifestations of Graft Rejection <br /> Hyperacute rejection<br /> Acute rejection<br /> Chronic rejection<br />9.3 Immunity to tumors<br />9.3.1 Cancer: Origin and Terminology<br /> Origin of Cancer<br /> Cancer associated genes<br /> Cancer induction process<br />9.3.2 Tumor immunology<br /> Tumor antigens<br />Identification of tumor antigens<br />Two types of tumor antigens<br />Tumor-specific transplantation antigens(TSTAs)<br />products of mutated oncogenes and tumor suppressor genes<br />products of other mutated genes<br />tumor antigens encoded by genomes of oncogenic viruses<br />Tumor-associated transplantation antigens(TATAs)<br />overexpressed and abnormally expressed cellular proteins<br />altered glycolipid and glycoprotein antigens<br />Tissue-specific differentiation antigens<br />oncofetal antigens<br /> Immune response to tumors<br />NK cells<br />macrophages<br />T cells<br />antibodies<br />9.3.3 Tumor Evasion of immune response<br />10. Immune Diseases <br />10.1 Hypersensitivity and Autoimmune diseases(Abnormal immune responses) <br />10.1.1 Effector mechanisms of abnormal immune responses and diseases<br /> Antibody mediated<br />Antibody-mediated<br />Antibody-antigen complex mediated<br /> T cells mediated<br />10.1.2 Hypersensitivity diseases<br /> Causes of hypersensitivity<br /> Types of hypersensitivity<br />Type I: IgE antibody mediated Immediate Hypersensitivity (uncontrolled or excessive responses against foreign antigens)<br />Components of type I hypersensitivity<br />Allergens<br />REAGINIC ANTIBODY (IgE)<br />Mast cells, basophils and eosinophile<br />IgE-BINDING Fc RECEPTORS<br />Sequence of events<br />Production of IgE<br />Binding of IgE to IgE Fc receptor on Mast cells and Basophiles<br />Activation of effector cells<br />Activation of Mast cells<br />Mediators produced by effector cells<br />Regulation of mast cell degranuation<br />Biological effect<br />Two effector phases of type I hypersensivity reactions<br />Early phase reaction(immediate)<br />Late phase reactions(2-4hours)<br />Detect Type I Hypersensitivity Reactions<br />Type I hypersensitivity diseases and therapies<br />Systemic/loclized anaphylaxis<br />SYSTEMIC ANAPHYLAXIS<br />LOCALIZED ANAPHYLAXIS (ATOPY)<br />ALLERGIC RHINITIS<br />Bronchial Asthma<br />Allergies of skin, upper respiratory and gut<br />Therapies<br />immunotherapy<br />therapeutic drugs<br />Pathogenesis of type I hypersensitivity<br />Genetic susceptibility<br />Hygene hypothesis<br />Type II: IgG antibody mediated Cytotoxic Hypersensitivity (immune antibody response against self-antigen) <br />Blood Transfusion Reactions<br />Hemolytic Disease of the Newborn<br />Drug-Induced Hemolytic Anemia<br />Type III: Antibody-antigen complex mediated Hypersensitivity (self antigens or foreign antigens with bound antibody)<br />Type IV: T cell mediated Hypersensitivity(Delayed type hypersensitivity, DTH): autoimmune response or response to foreign antigens <br />Effector functions<br />Phases of reaction<br />Detection<br />Diseases<br />10.1.3 Autoimmune diseases<br /> General properties of autoimmune disease<br /> Types of autoimmune diseases<br />Organ specific autoimmune diseases<br />Mediated by Direct Cellular Damage<br />Mediated by Stimulating or Blocking Auto-Antibodies<br />Systemic autoimmune diseases<br /> Proposed mechanism for induction of autommune diseases<br />Genetic basis of autoimmune disease<br />Role of infections in autoimunity<br />Release of Sequestered Antigens Can Induce Autoimmune Disease<br />Inappropriate Expression of Class II MHC Molecules Can Sensitize Autoreactive T Cells<br />Polyclonal B-Cell Activation Can Lead to Autoimmune Disease<br />10.2 Congenital and acquired immunodeficiencies (Lack of immune responses)<br />10.2.1 Congenital(Primary) immunodeficiencies<br /> Defects in innate immunity<br />defect in microbicidal activities of phagocytes<br />leukocyte adhesion deficiencies<br />defect in NK cells and other leukocytes: the Chediak-Higashi syndrom<br /> Defects in adaptive immunity<br />Defects in lymphocytes maturation<br />disorder of both B and T cells(severe combined immunodeficiencies, SCIDs)<br />X-linked SCID caused by mutation of the cytokine receptor commom g chain<br />SCID caused by Adenosine deaminase deficiency<br />defect in B cell maturation: X-linked agammaglobulinemia<br />defect in T cell maturation: DiGeorge syndrome<br />Defects in lymphocytes activation and function<br />defect in B cell activation and function<br />selective immunoglobulin isotype deficiencies<br />defects in B cell differentiation: common variable immunodeficiency<br />defect in T cell activation and function<br />Defect in T cell-dependent B cell activation: the X-linked hype-IgM syndrom<br />defects in T cell activation and function<br />Defects in MHC expression<br />10.2.2 Acquired(Secondary) immunodeficiencies<br /> Pathogenic mechanisms<br /> HIV and the Acquired Immunodeficiency Syndrome(AIDS)<br />Molecular and biologic features of HIV<br />HIV structure and Genes<br />Viral life cycle<br />entry<br />replication and regulation<br />package<br />The course of HIV disease<br />HIV infection<br />Steps in HIV infection and pathogenesis<br />HIV reservoirs and viral turnover<br />immune responses to HIV<br />mechanism of immunodeficiency<br />immune evasion by HIV<br />Treatment and prevention of AIDS<br />11. Immunotherapy: Manipulation of immune responses<br />11.1 Activation of immune respones<br />11.1.1 Vaccination against infectious agents<br /> Introduction<br />History of vaccine<br />Terminology of vaccination<br />Vaccine Classifications<br />Vaccines of two different strategies <br />Three basic vaccines<br />Other vaccines<br /> Passive and active immunization<br />Passive immunization<br />Common agents of passive immunization<br />Conditions that warrant the use of passive immunization<br />Advantage and disadvantage<br />Active immunization<br />Natrual infection<br />Vaccination programs<br />Vaccines for use in humans to date<br />Vaccines used in National Immunization Programs<br /> Requirements for effective vaccination<br />Vaccine types<br />Whole organism vaccine<br />Live attenuated vaccine<br />Inactivated vaccine<br />Subunit vaccine<br />DNA vaccine<br />Recombinant viral vector DNA vaccine<br />Recombinant plasmid DNA vaccine<br />Peptide vaccine<br />immunogenic peptide identification<br />problems and overcomes<br />TI antigen and conjugate vaccine<br />Adjuvant<br />microbial constituents<br />Complete Freund's Adjuvant(CFA)<br />Bacterial toxins(CT,LT) and derivatives<br />CpG containing DNA<br />Cytokines/chemokines<br />Live vectors<br />virus like particles<br />adjuvant as particulate delivery systems<br />micorspheres<br />liposomes<br />lipopeptides<br />single chain lipid<br />clustered lipid chain<br />Lipid core peptide(LCP) system<br />Rout of vaccination<br /> Designing of therapeutic vaccine to control existing chronic infections<br />Two cases of chronic infections<br />Treatment of chronic infections<br />11.1.2 Tumor immunotherapy<br /> Active immunotherapy<br />vaccination with tumor cells and tumor antigens<br />augmentation of host immunity to tumors by using cytokines and costimulators transfected tumor cells<br />nonspecific stimualtion of the immune system<br /> Passive immunotherapy<br />Therapy with anti-tumor antibodies<br />Adoptive cellular therapy<br />11.2 Suppression of immune responses<br />11.2.1 Immune tolerance or supression of allograft transplatation<br /> Immunosupression therapy of allograft rejection<br />General immunosuppressive therapy<br />Immunosuppression of T cells<br />plasmaphoresis<br />anti-inflammatory agents<br />Mitotic Inhibitors<br />Total Lymphoid Irradiation EliminatesLymphocytes<br />Specific immunosuppressive therapy<br />Monoclonal Antibodies Can Suppress Graft-Rejection Responses<br />Blocking Co-Stimulatory Signals to Induce Anergy<br /> Immune tolerance to allograft<br />11.2.2 Immunotherapy of hypersensitivity<br />11.2.3 Immunotherapy of autoimmune diseases<br /> T-Cell Vaccination Is a Possible Therapy<br /> Some experimental agents for immunointervention<br /> Oral Antigens Can Induce Tolerance<br />Immunolgy 1.1.1 Overview of immune responses in vivo 1.1.2 Classification 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 chemicalsblood proteins: complementcells: phagocytesadaptive 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 stimulationself-nonreactivity: also called self-tolerance. prevent to react against one's own cells.phases 5 phases:recognition of antigenactivation of lymphocytesantigen elimination (effector phase)homeostasismemory1.1.2.2 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 microbescell-mediated immunity mediated by T lymphocytes.principal defense against intracellular microbes. 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. <br /> <br />