Immunodeficiency Infections Tumors Hyperactive immune response Severe allergic reactions Autoimmunity

Immunity resistance of an organism to infection, disease, or other unwanted biological invasion exclusion from legal obligations, such as liabilities and punishments

Antigen - Proteins / polysaccharides (microbial / nonmicrobial) - Prompt generation of antibodies (binds to antigen) - Elicits an immune response (immunogen) - Exogenous / endogenous / self Epitope Immunologically active regions on antigen, that bind to specific membrane bound receptors on lymphocytes or to secreted antibodies

Antibody - Immunoglobulins (gamma globulins) found in blood and body fluids - Used by the immune system to identify and bind to antigens - Produced by B lymphocytes - Can belong to 5 classes IgG, IgA, IgM, IgE, IgD - Specificity is very high

Antibody - They have a basic unit of two light chains (κ and λ) and two heavy chains (γ, α, μ, δ, ε)

Antibody - Each antibody unit has two antigen binding sites (Fab) and one Fc Fab Fc

Immunoglobulins - Functions IgG: - Major component % of total immunoglobulin pool - Serum concentration is about mg/dl - Distributed evenly in the intra and extra vascular pools - Major antibody of the secondary (adaptive) immune response - Can move across placental barrier (passive immunity to new born)

Immunoglobulins - Functions IgM: - 10 % of total immunoglobulin pool. Exists as a pentamer - Serum concentration is about mg/dl - Largely confined to the intravascular pool - Rises early in response to infection / immune stimulus - Cannot move across placental barrier

Immunoglobulins - Functions IgA: % of total immunoglobulin pool. - Serum concentration is about mg/dl - Predominant antibody in body secretions (saliva, milk, gastro- intestinal, urine) - Exists as a non-secretory (monomer) and secretory (dimer) - Participates in mucosal immunity

Immunoglobulins - Functions IgD: - <1 % of total immunoglobulin pool. - Biological function unknown

Immunoglobulins - Functions IgE: - Very low levels in serum ( ng/ml) - Higher levels on surface membranes of basophils and mast cells, and in bronchial and conjunctival mucosa - Associated with allergic diseases such as asthma and hay fever, and with immunity to helminthic infestations

Immunity Innate (natural / native)(less specific) - Defense mechanisms present even before exposure to Ag. - Components - Epithelial barriers - Phagocytes - Natural Killer (NK) cells - Complement (activation through alternate and lectin path) - Toll Like receptors on phagocytes - Cytokines

Innate immunity: - Physical barriers - Skin, mucus membranes - Inflammatory barriers - Leakage of fluid containing chemical mediators - Chemical barriers - Lysozyme, complement, interferon, toll like receptors - Phagocyte barriers - Neutrophils, macrophages - Others - Natural Killer Cells

Natural Killer Cells (Large Granular Lymphocytes) % of peripheral blood lymphocytes - Have innate ability to kill tumor cells and virus infected cells, without prior sensitization - First line of defense against viral infections (? tumors) - Participates in antibody dependent cell mediated cytotoxicity

Adaptive Immunity (Acquired / Specific) (Immune response) Varicella zoster First exposure Recovery Subsequent exposures (Vaccination)

Effector response (first exposure) INFECTING AGENT IMMUNE REACTION ANTIGEN DESTRUCTION Disease Specific immune response Specific immune memory Lasts many years Recovery

Specific immune memory Specific antigen recognition INFECTING AGENT Memory response (subsequent exposures) ALMOST IMMEDIATE IMMUNE REACTION VERY RAPID ANTIGEN DESTRUCTION Rapid activation and amplification of immune response Enhancement of specific immune response NO DISEASE

Adaptive Immunity (Acquired / Specific) (Immune response) - T lymphocytes - B lymphocytes - Complement (classical pathway) - Antigen presenting cell - Cell mediated immunity (against intracellular microbes) - Antibody mediated immunity (against extracellular microbes and toxins)

Cell mediated immunity: T lymphocytes: - Thymus processed. Constitute 60-70% of blood lymphocytes - Localize in T zones of lymphocytes (para-cortical areas) and peri- arteriolar sheath of spleen - Express receptors that recognize MHC antigens - Can be activated ONLY by processed membrane bound antigens on antigen presenting cells - Express molecules on their surface called cluster determinants (CD) - CD4+ T cells (T helper cells) (60% of mature T cells) - CD8+ T cells (T suppressor cells) (30% of mature T cells)

CD4+ T helper cells: - Master regulator of immune response - Secretes cytokines that influence all other cells of immune system - Two subsets H T H 1 (secretes IL-2 and IFN- ϒ ) - facilitates delayed hypersensitivity, macrophage activation and opsonin synthesis T H 2 (secretes IL-4, IL-13, IL-5) - stimulates IgE synthesis and activation of eosinophils CD8+ cells act mainly as cytotoxic cells. H Also secrete cytokines similar to T H 1 cells

B Lymphocytes - Develop from immature precursors in the bone marrow - Constitute 10-20% of peripheral blood lymphocytes - In lymph nodes, found in the follicles. In spleen - white pulp - Express surface immunoglobulins - Surface IgM is involved in antigen binding

Antigen Presenting Cells (APC / accessory cells) - Cells capable of internalizing antigen (phagocytosis / endocytosis), process antigen and re-express it bound to MHC Class II - Three types of APC a) Dendritic cells b) Macrophages c) B Lymphocytes

Cytokines: (Messenger molecules) - Chemical messengers that mediate and regulate inflammatory, reparative and immunologic responses by effector cells. a) Cytokines that mediate innate immunity: Interleukin-1 (IL-1), Tumor Necrosis factor (TNF), Type 1 interferon, IL-6 b) Cytokines that regulate lymphocyte growth, activation and differentiation (IL-2*, IL-4, IL-12,IL-15, TGF-β). c) Cytokines that activate inflammatory cells (IFN-γ, IL-5, TNF) d) Cytokines that affect leukocyte movement (chemokines) e) Cytokines that stimulate hematopoiesis

Cytokines: (General properties) - Same cytokine may be produced by many cell types - Same cytokine may act on many cell types (pleiotropic action) - Act in 3 ways a) On the same cell that produces them (autocrine) b) On the other cells in the vicinity (paracrine) c) On remote cells systemically (endocrine) - Mediate effects by binding to specific high affinity receptors

MHC Molecules - Large genomic region (gene family) found in all vertebrates - Plays an important role in Immune system Autoimmunity Transplantation Reproductive success

MHC Molecules - Antigens of MHC are expressed on the surface of many cells - Principal function of these is to bind peptide fragments of foreign proteins for presentation to antigen specific T cells - Genes are located on chromosome 6 - System is highly polymorphic - Three categories of MHC genes Class I and Class II are involved in antigen presentation Class III encode complement proteins

MHC Molecules - Role of MHC (HLA) complex: a) Organ transplantation: recipient’s immune system recognizes donor organ HLAs and accept / reject it b) Regulation of immune system: Class I antigens regulate function of CD8+ cells in viral infections Class II antigens regulate function of CD4+ cell