IMMUNE MECHANISM-II

IMMUNE MECHANISMS-IIDr Ambika JawalkarClassification of Immunity

ANTIGEN

Epitopes / determinant sitesParatopeHapten / Incomplete antigenImmunogenicity of antigen is determined by,Size of moleculeForeignnessChemical structureSusceptibility of the substance to the tissue enzymesGenetic constitution of the hostDosage, route & timing of administration

Histocompatability AntigensAntigens present on the plasma membrane of cells of each individual of a species

Encoded by genes called histocompatability genes which are collectively called as MHC Major Histocompatability Complex

Genes for MHC are located on chromosome 6, clustered in a multigene complex of classes I, II, III

9Functions of MHCClass I markers that display unique characteristics of self molecules & regulation of immune reactionsRequired for T lymphocytesClass II receptors that recognize & react with foreign antigens. Located primarily on macrophages & B cellsInvolved in presenting antigen to T cellsClass III secreted complement components, C2 and C4No two persons except identical twins have the same MHC Proteins

No two persons can have same MHC proteins on plasma membranes of their cells

HLA Tissue TypingANTIBODIES / IMMUNOGLOBULINSGamma GlobulinsAll antibodies are Igs, but all Igs are not antibodies

Formation of Antibody

IgG

Structure: MonomerPercentage serum antibodies: 80%Location: Blood, lymph, intestineHalf-life in serum: 23 daysComplement Fixation: YesPlacental Transfer: YesKnown Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn.IgA

Structure: DimerPercentage serum antibodies: 10-15%Location: Secretions (tears, saliva, intestine, milk), blood and lymph.Half-life in serum: 6 daysComplement Fixation: NoPlacental Transfer: NoKnown Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tractIgM

Structure: PentamerPercentage serum antibodies: 5-10%Location: Blood, lymph, B cell surface (monomer)Half-life in serum: 5 daysComplement Fixation: YesPlacental Transfer: NoKnown Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigensIgD

Structure: MonomerPercentage serum antibodies: 0.2%Location: B-cell surface, blood, and lymphHalf-life in serum: 3 daysComplement Fixation: NoPlacental Transfer: NoKnown Functions: In serum function is unknown. On B cell surface, initiate immune responseIgE -

Structure: MonomerPercentage serum antibodies: 0.002%Location: Bound to mast cells and basophils throughout body. Blood.Half-life in serum: 2 daysComplement Fixation: NoPlacental Transfer: NoKnown Functions: Allergic reactions. Possibly lysis of worms

Development of AMI / HIRole of AMI

Provides defence against most extracellular antigensParticipates in type I, II & III hypersensitivity reactionsAssociated with certain autoimmune diseases

Types of AMI responsePrimary Humoral responseSecondary Humoral response

Stages of Humoral Immune Response Antigen processing & presentationRecognition of Antigen by LymphocytesLymphocyte activationProduction of antibodiesInactivation of antigen / attack phase / effector phase1. Antigen processing & presentationAPCs- Macrophages- B-lymphocytes- Dendritic cells / Langerhans cells2. Recognition of Antigen by Lymphocytes

B-cells contain surface Igs as receptorsT-cells contain TCRs chain chainEpitope-binding siteVariable regionConstant regionTransmembrane region3. Lymphocyte activation

Blast transformation

T-B cooperation

B- cells form clones - Plasma cells- memory B-cells

4. Production of antibodies

Theories of antibody productionInstructive / template theories- Direct template theory- Indirect template theorySelective theories- Side chain theory-Natural selection theory-Clonal selection theory5. Inactivation of antigen / attack phase / effector phase

Direct attack on invading agents* Agglutination * Precipitation* Neutralization* Cytolysis

Attack through Complement system

CLASSICAL PATHWAYALTERNATIVE PATHWAYDevelopment of CMIRole of CMIProtects against fungi, most of viruses & intracellular bacteriaParticipates in allograft rejection & GVHDParticipates in delayed hypersensitivity reactionProvides immunological surveillance & immunity against cancerStages of Cellular Immune Response Antigen processing & presentationRecognition of Antigen by LymphocytesT lymphocyte differentiation / activation Attack phase 1. Antigen processing & presentationAPCs- Macrophages- B-lymphocytes- Dendritic cells / Langerhans cellsProcessing of phagocytosed materialMHC-I (bacterial antigens)Processing of antigen derived within cellMHC-II (viral antigens)2. Recognition of Antigen by Lymphocytes

3. T lymphocyte differentiation / activation

T-T Cooperation 4. Attack phase

Role of Tc cells* perforin mediated killing* Lysis through cytotoxic substances* Induction of apoptosisRole of TH cells*TH-1 cellssecrete cytokines like IL-2, INF- & TNF-*TH-2 cells secrete IL-4,5,6,10 &13Role of Ts cells*regulate activity of Tc cells

CMI is a balance between Tc cells & Ts cells

Other immune mechanism related aspects Immune Tolerance Immune Modulation Autoimmunity Hypersensitivity Immunodeficiency diseases Autoimmunity

Systemic lupus erythematosusRheumatoid arthritisEndocrine autoimmunitiesMyasthenia gravisMultiple sclerosis

39

40

Hypersensitivity