Immunity Dr Asma Jabeen Assistant Professor Physiology Learning Objectives At the end of this session, the student should be able to: •Define immunity and contrast the difference between its 2 types (innate & acquired). • Describe some mechanisms for innate immunity (interferon’s & complement should be included). • Identify the major differences between the two types (humoral& cell-mediated) of acquired immunity. • Relate the knowledge acquired to some clinical problems (e.g., AIDS) The ability of the human body to resist almost all types of organisms and toxins that tend to damage the tissues and organs is called IMMUNITY. It of two types; Innate immunity Acquired immunity Immune defenses can be classified into 2 types which usually interacts: Nonspecific immune defenses (Innate Immunity) Specific immune defenses (Acquired Immunity) Protect against microbes or Protect against microbes to F.B. (invaders) without having which the body is previously to exposed (recognized before) either recognize their specific identity. through The mechanisms used are immunization. not specific to any invader. The infection mechanisms used specific for each invader. or are Innate Immunity Acquired Immunity Specificity Non-specific Specific i.e., Reacts to invaders from i.e., Reacts to a specific different type invader each time and can not react to another. Diversity Limited Very high i.e., Although the cells are of the same type, each group shows totally different surface molecules. Memory No Yes Remembers the invader on reexposure. Non-reaction to self Yes Yes Components Cells Phagocytes killer cells Molecules Complement & natural Lymphocytes Antibodies Innate Immunity Also called natural/non specific immunity It is the inborn capacity of the body to resist the entry of microorganisms in the body It results from general processes, rather than from processes directed against specific disease organisms Innate immunity includes: Phagosytosis of invaders by white blood cells Destruction of swallowed organisms by acid secretions of stomach Resistance of skin to invading organisms Presence of certain chemical compounds in blood : • Lysozyme • Basic polypeptides • Complement complex • Natural killer lymphocytes Complement System The Complement system is the system of twenty proteins, present normally among the plasma proteins many of which are enzyme precursors. Main eleven proteins C1 to C9, B and D Complement family of plasma proteins which is involved in: 1) killing of microbes without prior phagocytosis. 2) Opsonization: making phagocytosis easier. 3) Chemotaxis: Direction of phagocytes toward the source of infection. Opsonization Effects of complement activation Opsonization and phagocytosis C3b Lysis (lytic complex) Agglutination Neutralization of viruses Chemotaxis C5a Activation of mast cells and basophils (C3a,C4a,C5a) Inflammatory effects Interferon One of the innate defense mechanism is the release of interferon from virus infected cells. Interferon briefly provides non specific resistance to viral infections by transiently interfering with replication of the same or unrelated viruses in other host cells. In fact, interferon was named for its ability to interfere with viral replication Interferon has following effects: Antiviral effects Anticancer effects Mechanism of action: It markedly enhances the actions of natural killer cells and cytotoxic cells, which attack and destroy both virus infected cells and cancer cells. Interferon itself slows cell division and suppress tumor growth Interferons are a family of cytokines that nonspecifically inhibit viral replication inside host cells Acquired Immunity It is extremely powerful specific immunity that develops against an individual invading agent, after the body is first attacked by a bacterium, virus, toxin or foreign tissues from other animals. Types of acquired immunity Humoral immunity or B-cell immunity Cell- mediated immunity or T-cell immunity Millions of different types of preformed B- lymphocytes and T-lymphocytes, capable of forming antibodies or T cells are stored in lymph tissues. Each is capable of forming one type of antibody or activated T-cell against one specific type of antigen. Humoral Immunity After antigen presentation to specific B-lymphocyte, Bcell enlarge and become lymphoblast Plasmablast Divides once every ten hrs For nine divisions 500 plasma cells (in 4 days) 2000 molecules of antibodies/sec for each plasma cell, enter into lymph and blood Subsequent exposure to the same antigen causes much more rapid and much more potent antibody response. BECAUSE ! ! There are many more memory cells than there were original B-lymphocytes of the specific clone. Classes of antibodies Five classes of antibodies IgM Most effective, primary response IgG 75% of total antibodies in body Opsonization, cross placenta IgE Allergy IgA Secretions IgD Helps cytotoxic cells Cell-Mediated Immunity On stimulation by a proper antigen, presented by antigen presenting cells,T-lymphocytes of a specific lymphocyte Clone proliferate and release large number of activated, specifically reacting T-cells into the lymph. Formation of T-lymphocyte Memory cells On activation of a clone of T-lymphocyte by an antigen, many of the newly formed lymphocytes are preserved in the lymphoid tissues to become additional T-lymphocytes of that specific clone. On second exposure to that specific Antigen anywhere in the body release of activated T cells is much rapid and much more powerful. Types of T-cells Helper T cells Cytotoxic T cells Suppressor T cells OR regulatory T cells Helper T cells Most numerous Major regulator of virtually all immune functions Form protein mediators called lymphokines Cytotoxic T cells Also called “KILLER CELLS” Capable of killing micro-organisms and at times even body’s own cells Secrete hole forming proteins called “perforins” Cytotoxic cells are especially lethal to tissue cells invaded by viruses Act against cancer cells, heart transplant cells and other cells foreign to the person’s own body Direct destruction of an invading cell by sensitized lymphocytes Suppressor T cells They are capable of suppressing the functions of both cytotoxic and helper T Cells. Prevent excessive immune reactions Important role in immune tolerance Humoral Immunity Cell mediated immunity Main cells Maturation B lymphocytes Generated and matured in bone marrow T lymphocytes Originate in bone marrow and complete development in thymus Protect against Extracellular Intracellular microbes microbes and their 1.viruses toxins 2.parasites 1.toxin induced (leishmania) diseases 3.bacteria 2.infections (virulence (mycobacteria, related to listeria) polysaccharide 4.kill tumor cells capsule) End result of activation Differentiation of B cells into antibody secreting cells called plasma cells Hypersensitivity reactions I, II, III are antibody mediated Secrete locally acting proteins called cytokines IV is cell mediated Regulator of antibody synthesis No Yes Onset Rapid Delayed type hypersensitivity Antibodies Evaluation Formed Not formed From plasma Skin test for level of antibodies development of delayed type of hypersensitivity Cells involved Ab synthesis requires 3 cells: 1.t lymphocytes 2.b lymphocytes 3.macrophage 1.macrophage 2.helper T cells 3.natural killer T cells 4.cytotoxic T cells