Immunity

CHAPTER 22

Introduction
The ability of the body to ward off disease is called resistance, and the converse is susceptibility. Pathogens:disease producing microbes. Nonspecific resistance includes dense mechanisms that provide immediate but general protection against invasion by a wide range of pathogens. Specific resistance or immunity develops more slowly and involves activation of specific lymphocytes that combat a particular pathogen or other foreign substance. The body system responsible for immunity is the lymphatic system.

Nonspecific Resistance To Disease

This lacks specific responses to specific invaders. Mechanisms include the eternal mechanical and chemical barriers provided by the skin and mucous membranes. Also various internal nonspecific defenses including antimicrobial proteins, natural killer cells and phagocytes, inflammatory and fever.

First Line of Defense

These are the first line of defense against pathogens. Epidermis-a formidable physical barrier. Periodic shedding removes microbes. The epithelial layer of mucous membranes secrete a fluid called mucus that lubricates and moistens. This can also trap microbes and foreign substances. The upper respiratory tract in addition also have cilia. Waiving action of cilia. Other fluids -lacrimal apparatus produce tears. Salivawashes microbes from surface of teeth. Urine-retards colonization of microbes.

First Line of Defense

Defecation and Vomiting-expel microbes. Sebaceous glands-sebum inhibit growth of certain bacteria. Perspiration-helps flush microbes from the surface and also contains lysozyme which is antimicrobial. Gastric juice-a mixture of HCl, enzymes and mucus. Destroys bacteria. Vaginal secretions-also acidic and destroy bacteria.

Second Line of Defense

This includes antimicrobial proteins, phagocytic and natural killer cells, inflammation and fever. Antimicrobial proteins: blood and IF contain three main types of antimicrobial proteins.
Interferons: lymphocytes, macrophages and fibroblasts infected with virus produce interferons (IFNs). They stop replication of viruses. Three types-alpha, beta and gamma. Complement: a group of normally inactive proteins in the blood plasma and on plasma memb. When activated they complement or enhance certain immune, allergic and inflammatory reactions. Transferrins: iron-binding proteins. Inhibit growth of bacteria by reducing amount of iron.

Second Line of Defense

Natural Killer cells and Phagocytes
NK cells:these are lymphocytes. They can kill a wide variety of microbes plus tumor cells. About 5-10% blood lymphocytes are NK cells. Also present in the red bone marrow, spleen, lymph nodes. NK cells achieve destruction in two ways-by releasing perforins or by binding to target cell and destroying it.

Second Line of Defense

Phagocytes: perform phagocytosis. Two major types are macrophages and neutrophils. Wandering and fixed macrophages (histocytes in the skin, Kupffer cells in liver, microglia in NS, tissue macrophages). Phagocytosis has several phases: chemotaxis, adherence, ingestion, digestion, and killing.
Chemotaxis-chemical attraction of phagocytes to a particular location. Adherence-attachment to surface of microbe ingestion-engulfing digestion-merges with lysosomes killing.

Inflammation
Cells damaged by microbes or physical or chemical agents can also initiate a defensive response called inflammation. Signs are redness, pain, heat and swelling. Inflammation traps microbes, toxins and foreign material at the site of injury and prepares the site for injury repair. It helps restore tissue homeostasis.

Stages of Inflammation
Vasodilation and increased permeability: more blood flows and allows for antibodies, clotting proteins and phagocytes to pass out readily. This is done by release of histamine by mast cells, basophils and platelets. Kinins. Prostaglandinsintensify the effect. Leukotrines:basophils and mast cells inc. permeability. Complement-promote phagocytosis. This produces heat, redness(erythema) and edema

Stages of Inflammation
Phagocyte emigration (diapedesis): this depends on chemotaxis. Neutrophils, kinins, complement. Inc in WBCsleukocytosis. Neutrophils dominate first. Monocytes follow which then transform to macrophages. tissue repair-pus formation. Pus is destroyed and over a period of days is destroyed.

Fever
Fever is an abnormally high body temperature. It occurs during infection and inflammation. Elevated temp. intensifies effects of interferons, inhibits growth of microbes and speeds up body reactions that aid repair.

Specific Resistance-Immunity
Defense against specific antigens is immunity. Diff. From non-specific in two ways: specificity and memory. Immunolgy immune system

Types of Immune Responses

Cell-mediated immune response-T8(CD8+) cells proliferate into killer T cells and directly attack the invading antigen. Effective against intracellular pathogens, cancer cells and foreign tissue transplants. In the second kind called-antibody mediated (humoral) immune response, B cells transform into plasma cells which secrete antiobodies or immunoglobulins. Effective against antigens present in body fluids, extracellular pathogens that multiply in body fluids but rarely enter body cells. Most T4 cells become helper cells that aid in the above two responses.

Antigens
Antigens have two important characteristicsimmunogenecity and reactivity Immunogenecity: ability to provoke an immune response. Reactivity-ability of antigen to react specifically with an antibody. Complete antigen has both. Entire microbe or parts of microbe can act as antigens. Antigens that get past nonspecific defense have three routes-enter blood stream and are deposited in the spleen, enter lymphatic vessels and reach lymph nodes or lodge in MALT.

Chemical Nature of Antigens

Large, complex molecules that are usually proteins. Could be NA, lipoproteins, glycoproteins, polysaccharides. T cells respond only to protein antigens. B cells to others also. A smaller substance that has reactivity but no immunogenecity is called hapten. Epitopes: small, specific portions of antigen that trigger an immune response. Also called antigenic determinants. MHC -I and II. Function to help T cells to recognize an antigen is foreign and not self.

Cell-Mediated Immunity
This begins with activation -antigen recognition and costimulation-of a small number of T cells by a specific antigen. Then proliferation and differentiation into clone of effector cells. This occurs in secondary lymphatic organs and tissues. Finally elimination of intruder.

Types of T cells
Helper T cells-T4 (CD4) cells. Cytotoxic T cells-T8 (CD8) or killer T cells. Memory T cells-T cells that remain from a proliferated clone after a cell mediated response. Cytotoxic cells are the actual eliminators. By perforin or lymphotoxin mechanisms.

Antibody-Mediated Immunity
In the presence of a foreign antigen, specific B cells in the spleen, lymph nodes or lymphatic tissue in GI tract become activated. They differentiate into plasma cells that secrete antibodies which in turn circulates in the lymph and blood to reach the site of invasion. The ones that do not differentiate as plasma cells remain as memory B cells that are ready to respond more rapidly and forcefully should the same antigen reappear at a future time.

Antibodies
An antibody can specifically combine with the epitope of an antigen. Its structure matches its antigen much as a lock fits a specific key. Antibodies belong to a group of glycoproteins called globulins, called immunoglobulins. (IgGs). Most antibodies contain four polypeptide chains-two are identical and are called H chains, the other two also identical are the light L chains. Within each H and L chains are two regions V-antigen binding site and C-constant region. Constant region of H varies between IgG,IgA,IgM,IgDandIgE.

Action of Antibodies
Neutralization:neutralizes the damaging effect. Immobilization of bacteria: bacteria lose motility. Agglutination and precipitation of antigen:clumping together. Activation of complement: enhancement of phagocytosis: they enhance the activation of phagocytes by causing agglutination and precipitation, by activating complement and by coating microbes making them more susceptible-opsonization.

Complement System
This is a defensive system consisting of plasma proteins that attack and destroy microbes. It is an ordered sequence or cascade of reactions. Two-classical and alternate. In classical the antibody binds to antigen. In alternate there is interaction between polysac.on surface of microbe and factors B,D and P. The consequence of the two are: activation of inflammation,, opsonization and cytolysis.

Immunological Memory
Immunization against certain microbes is possible because memory B cells and memory T cells remain after a primary response. The secondary response provides protection should the same microbe enter the body again. Active immunity vs. passive immunity. Natural vs. artificial.

Aging and The Immune System

Elderly individuals are more susceptible to infections. Response to vaccines is lowered and produce more autoantibodies. T cells become less functional. Age related atrophy of thymus. B cells also less responsive.