Chapter 43 Immune System

Innate Immunity This type of immunity is present before any exposure to pathogens and begins at birth Largely nonspecific Skin is the first line of defense Mucous membranes that line the digestive, respiratory, and genitourinary tracts Tears, sweat, and saliva are body secretions that serve this type of immunity Lysozyme is an antimicrobial protein found in the skin and mucous membrane that digests cell walls of bacteria

Innate Immunity If microbes make it past the external defenses then cellular and chemical defenses take over White blood cells that serve as phagocytes that engulf and destroy microbes - also initiate the inflammatory response Four types of phagocytic WBC: 1. Neutrophils – most abundant; life span a few days 2. Macrophages – larger, longer living WBC, but only 5% in circulation; found in spleen, lymph nodes 3. Eosinophils – low activity, but essential to defend against multicellular parasites 4. Dendritic cells – ingest much like macrophages

Phagocytosis

Innate Immunity Antimicrobial proteins directly attack proteins or impede their reproduction - complement system – 30 serum proteins that are inactive without microbes -trigger cascade of steps that lyse invading cells; also trigger inflammation Interferon (alpha & beta) – proteins that defend against viral infections - secreted by virus infected cells to induce other cells to produce substances to inhibit further infection

Innate Immunity Inflammatory response – triggered from injury or entry of pathogens to a site of body - Mast cells found in connective tissue release histamine - release will trigger dilation and permeability of capillaries - increased blood flow causes redness and heat - vascular changes deliver antimicrobial proteins and clotting elements to site which begins repair and blocks spread to other parts of body - Chemokines – small proteins that direct the migration of phagocytes and increase production of microbe killing compounds

Inflammatory Reponse

Innate Immunity Fever is another systemic response in which toxins from pathogen and substances from macrophages set body’s temperature higher Natural Killer cells – nonspecific – patrol and attack virus infected or cancer cells - surface receptors recognize the target and release chemicals that cause apoptosis or programmed cell death

Summary

Acquired Immunity Develops only after exposure to inducing agents and is highly specific Cytokines proteins secreted from macrophages that activate the specific WBC called lymphocytes Antigen – any foreign molecule recognized by lymphocytes and elicits a response epitope – binding or recognition site on the antigen that elicits a response Antibodies – defensive proteins released by lymphocytes that recognize the epitope of antigens and target them for destruction

Acquired Immunity Two types of lymphocytes: 1. B Lymphocytes 2. T Lymphocytes Both use antigen specific receptors to recognize antigens B cells recognize intact antigens, whereas T cells can recognize fragments of antigens

Acquired Immunity Major Histocompatibility Complex (MHC) – family of genes that normal cell surface proteins - these proteins attach to antigens and present them to the surface of the plasma membrane for recognition by a particular T cell - Class I MHC – found on almost all nucleated cells of the body and recognized Cytotoxic T cells - Class II MHC – made by dendritic, macrophages and B cells and recognized by Helper T cells

Lymphocyte Development Both lymphocytes develop from pluripotent stem cells - T cells – migrate to thymus, gland of thoracic cavity, during maturation - B cells – stay in bone marrow during maturation (bursa of Fabricius) Three key events of lymphocytes 1. maturation of B cell in marrow 2. maturation of T cell in thymus 3. Lymphocyte encounters and binds to antigens leading to activation, proliferation, and differentiation – clonal selection

Clonal Selection Clonal selection – antigen driven cloning of lymphocytes that selectively activates tiny fraction of cells that are specific for and dedicated to eliminating that antigen - effector cells – clone of large numbered short lived cells that combat antigen - memory cells – long lived cells bearing receptors specific for same inducing antigen

Clonal Selection Primary immune response – proliferation and differentiation of lymphocytes the first time the body is exposed to antigen - response peak in 10-17 days Secondary immune response – exposure to the same antigen that produces a faster, more prolonged response of greater magnitude

Acquired Immunity Two branches of immunity: 1. Humoral response – involves activation and clonal selection of B cells that release antibodies into blood and lymph 2. Cell-mediated response – activation and clonal selection of cytotoxic T cells that directly destroy target cells

Acquired Immunity Central to humoral and cell mediated responses is the helper T cell - CD4 is a surface protein on the helper T cell that binds the class II MHC - keeps helper T and antigen presenting cell joined during activation of helper T clones and memory cells - leads to secretion of cytokines that stimulate other lymphocytes

Acquired Immunity Cytotoxic T cells target virus infected cells and cancer cells - utilize CD8 surface protein that behaves like CD4 in helper T cells - Activated Cytotoxic T cells secrete proteins that act on bound infected cell and destroy it - exposes pathogen to antibodies

Antibody Classes 5 classes - binding sites are responsible for identification of antigens - tails are responsible for antibody distribution and mediation of antigen disposal

Antibody Disposal 5 mechanisms of disposal by antibodies 1. Viral neutralization – binding of proteins to surface blocks ability to infect host 2. Opsonization – bound antibodies enhance macrophage attachment to microbes and increase phagocytosis 3. Agglutination – clumping of bacteria or viruses forms aggregates that can be readily phagocytosed by macrophages 4. Precipitation – antibodies cross link soluble antigen molecules dissolved in body fluids making them immobile and easily targeted by phagocytes 5. Complement system – binding of antigen-antibody complex causes complement proteins to activate a cascade of reactions that generate a Membrane Attack complex (MAC) *forms a pore in membrane, ions and water rush in and cause cell to swell and lyse

Active & Passive Immunity Active immunity – occurs by natural exposure to infectious agent -can develop from immunizations or vaccinations with inactivated form of bacterial toxin, microbe, parts of microbe, genes of microbial proteins Passive Immunity – conferred by transferring antibodies from one immune individual to one that has not been exposed to agent Ex: mother passing antibodies to fetus through colostrum

Blood Groups and Transfusions Blood types contain antigens that the body recognizes as self and non-self Ex: Type A blood with A antigens is tolerant, but Type B blood will generate antibodies and lead to a transfusion reaction that can involves lyses of red blood cells and can lead to chills, fever, shock, and kidney malfunction

Blood Groups Rh factor – red blood cell antigen that triggers antibodies (IgG) to mount a humoral response on fetus - Mothers can be injected with anti-Rh IgG antibodies to prevent attack on future fetuses

Allergies Allergies – exaggerated or hypersensitive responses to a certain antigen or allergen Most common allergies involve IgE antibodies ( hay fever) induction of mast cells cause release of histamine that dialates blood vessels - symptoms runny nose, sneezing, tearing eyes Antihistamines block histamine receptors and diminish allergy symptoms Anaphylactic shock – whole body, life threatening reaction with exposure to antigen Ex: peanut allergies, bee stings

Autoimmune Disease Immune system loses tolerance of self and turns against certain molecules of body - releases antibodies against self molecules like histones and DNA - thought to arise from some failure of immune system regulation