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The Immune System • Chapter 43 ~ Lines of Defense Nonspecific Defense Mechanisms…… PCA: • List the organs involved in the immune sytem: Innate Immunity: • Specialized phagocytic white blood cells • Antimicrobial proteins • Inflammatory response Innate Immunity: 5 types of Leukocytes • Neutrophils • 60-70% WBCs; engulf and destroy microbes at infected tissue Short lived • Monocytes • 5% WBCs; develop into…. • Macrophages 1)phagocytosis • 2)lysosomal enzymes destroy microbes • Dendritic cells: • Stimulate development of the acquired immune system Innate Immunity: 5 types of Leukocytes • Eosinophils • 1.5% WBCs; destroy large parasitic invaders • Enzymatic action- no phagocytosis • Natural killer (NK) cells • destroy virus-infected body cells & abnormal cells • apoptosis Antimicrobial Proteins: 1. Complement system- group of 30 proteins Once activated can cause invading cells to lyse – burst 2. Interferons (α, β and γ) Immune response to viruses Activates macrophages The Inflammatory Response • Tissue injury; release of chemical signals~ • histamine (basophils/mast cells): causes Step 2... • prostaglandins: increases blood flow & vessel permeability • Dilation and increased permeability of capillary~ • chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs • Phagocytosis of pathogens~ • fever: leukocyte-released molecules increase body temperature Acquired Immunity: • Lymphocyctes •pluripotent stem cells... • B Cells (bone marrow) • T Cells (thymus) • Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms) • Antibodies: antigen-binding immunoglobulin, produced by B cells • Antigen receptors: plasma membrane receptors on B and T cells Acquired Immunity: •Epitope- antigenic determinant • Small area on antigen recognize by lymphcyte T cell receptors and MHC: • Major Histocompatibility Complex (MHC) • Antigen presentation- bind to fragments and bring them towards the cell surface • Two classes: • Class I MHC • Class II MHC MHC • Class I MHC(nucleated body cells): recognizes antigen fragments in the cell, binds to them and displays them at the cell surface – Cytotoxic T cells will bind and destroy fragments • Class II MHC: recognizes antigen fragments in the cell, binds to them and displays them at the cell surface – Helper T cells will bind and initiate a process to destroy fragments Cytotoxic T cell mechanism • Destroy cells infected by intracellular pathogens and cancer cells • Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC) • cell lysis and pathogen exposure to circulating antibodies Cytotoxic T cell mechanism: • the activated cytotoxic T cells release: – perforins which form pores in the target cell membrane – and proteolytic enzymes which enter the cell via endocytosis and initiate apoptosis • Cytotoxic T cell becomes first activated by the secretion of cytokines from helper T cells Cytotoxic T cell mechanism Helper T cell mechanism: • Function in both humoral & cell-mediated immunity • Stimulated by antigen presenting cells • T cell surface protein CD4 enhances activation(similar to CD8 of class II MHC) • Cytokines secreted (stimulate other lymphocytes): • a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells • b) interleukin-1 (IL-1): activates helper T cell to produce IL-2 Helper T cell mechanism: • a helper T cell recognizes the complex becomes activated with the aid of cytokines secreted by the macrophage forming a clone of activated helper T cells • an activated T cell binds to the B cell • B cell becomes activated with the help of cytokines Helper T cell mechanism Clonal Selection: • 1. antigen binds to antigen receptors of a specific lymphocyte • 2. the selected lymphocyte proliferates forming a clone of identical cells bearing the same receptors • 3. some of the proliferated cells develop into shortlived effector cell(plasma cell if B lymphocyte, helper T cell or cytotoxic T cell if T lymphocyte) that secrete antibodies specific for the antigen or destroy the antigen • 4. some proliferated cells develop into long lived memory cells that can respond rapidly upon exposure of the same antigen Clonal Selection Induction of Immune Responses •primary immune response- the selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to a particular antigen (10-17 days) •secondary immune response- if individual is exposed again to the same antigen, the response is faster( 2- 7 days)- immunological memory Induction of Immune Responses Types of immune responses • • • • Humoral immunity B cell activation Production of antibodies Defend against bacteria, toxins, and viruses free in the lymph and blood plasma • Cell-mediated immunity • T cell activation • Binds to and/or lyses cells • Defend against intracellular pathogens such as bacteria, viruses, fungi, protozoa, and parasite s; and cancer cells Humoral response: B cells • Stimulated by T-dependent antigens (help from TH cells) • Macrophage (APCs) with class II MHC proteins • Helper T cell (CD4 protein) • Activated T cell secretes IL-2 (cytokines) that activate B cell • B cell differentiates into memory and plasma cells (antibodies) Antibody Structure & Function • Epitope: region on antigen surface recognized by antibodies • 2 heavy chains and 2 light chains joined by disulfide bridges • Antigen-binding site (variable region) 5 classes of Immunoglobins • • • • • IgM: 1st to circulate; indicates infection; too large to cross placenta IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration IgD: do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells IgE: very large; small quantity; releases histamines-allergic reaction Antibody-mediated Antigen Disposal • Opsonization: antibody binds to and blocks antigen activity-coats antigen surface enhancing macrophage activity • Agglutination: antigen clumping- antibodies contain at least two antigen binding sites • Precipitation: cross-linking of soluble antigensforms immobile aggregates that are disposed of by phagocytosis • Viral Neutralization: antibodies bind to certain proteins on the surface of a virus blocking its ability to infect a host cell Immunity in Health & Disease • Active immunity • natural: conferred immunity by recovering from disease • Active immunity • artificial: immunization and vaccination; produces a primary response • Passive immunity: transfer of immunity from one individual to another • natural: mother to fetus; breast milk • artificial: rabies • Transfer of antibodies from rabid(immune) animal to non-rabid (non-immune) animal Self/Nonself Recognition • Self-tolerance: capacity to distinguish self from non-self • Autoimmune diseases: failure of self-tolerance; multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus Blood Group and Transfusions: • See PCA: Explain why blood type AB is considered the universal recipient and blood type O is considered the universal donor? Abnormal immune function • Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability • Allergy symptoms can be diminished with antihistamines – The hormone epinephrine counter acts this allergic reaction • Autoimmune disease: • Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S. Essay: 10pts. • 1. Describe the main role of the following cells types: helper T cells, cytotoxic T cells and B cells. • 2. What is responsible for the activation of these molecules? • 3. What deficiencies, if any would result from an individual born without a Thymus?