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5b. Acquired Immunity

Course: MBI 111, Spring 2008
School: Miami University
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Word Count: 1912

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Human 5. Host Defenses Against Parasitism: Acquired Strategies - Acquired Immunity Third-Line Defenses Acquired Immunity Acquired Immunity acquired immunity: resistance acquired against specific antigens antigens: chemicals that elicit a response by the body's immune system (abbreviated Ag) important features nonself: not normally found in one's body immunogenic: stimulates production of immune cells...

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Human 5. Host Defenses Against Parasitism: Acquired Strategies - Acquired Immunity Third-Line Defenses Acquired Immunity Acquired Immunity acquired immunity: resistance acquired against specific antigens antigens: chemicals that elicit a response by the body's immune system (abbreviated Ag) important features nonself: not normally found in one's body immunogenic: stimulates production of immune cells reactive: can react with immune cells or their products 2 Third-Line Defenses Acquired Immunity diverse nature: milk proteins insect venom blood components organ transplants microbial components 3 Acquired Immunity Antigens typically macromolecules: large complex chemical compounds generally > 10,000 molecular weight (measured in daltons, hydrogen molecule is 1d) chemical composition (ranked strongest to weakest antigenically) protein - largest array of building blocks polysaccharides (capsule, A and B blood group Ag) weaker due to lack of chemical diversity DNA and lipids are poor antigens - limited diversity The number of building blocks and the size contribute to the likelihood of a unique combination of building blocks being present in the Ag 4 Acquired Immunity Antigens epitope: a unique site on antigen which is recognized ~6-8 amino acids or carbohydrate molecules long antigens typically have more than one epitope (many) hapten: a small molecule that complexes with self molecule to form Ag acts as epitope (e.g. penicillin combines with self protein allergic response) 5 Acquired Immunity Antigens Specific Immune Tolerance immunity theory proposed by Burnet and Talmadge (1957) person's own protein and polysaccharide do not stimulate immune response (interpreted as "self") before birth, potential Ags contact and inactivate immune system cells that might respond to them becomes tolerant to "self" and respond only to "nonself" 6 Acquired Immunity Antigens Specific Immune Tolerance Self immunity theory proposed by Burnet and Talmadge (1957) person's own protein and polysaccharide do not stimulate immune response (interpreted as "self") before birth, potential Ags contact and inactivate immune system cells that might respond to them generates a repertoire of lymphocyte clones, each with unique receptor display becomes tolerant to "self" and respond only to "nonself" Lymphocyte stem cell Eliminated clones Self Receptors 7 Acquired Immunity Antigens Types of Antigens autoantigens: "self" Ag that elicit an immune response basis of autoimmune disease alloantigens: Ag found in some but not all members of a species ABO blood group Ags Rh Ag tissue-typing Ag (MHC - major histocompatibiity complex) 8 Acquired Immunity Cells of the Immune System Blood Components serum: fluid containing minerals, salts, proteins plasma: serum containing clotting agents cells: (from bone marrow) red blood cells white blood cells platelets 9 Acquired Immunity Cells of the Immune System erythrocytes: RBCs carry oxygen and CO2 in hemoglobin upon death, hemoglobin converted to bilirubin (yellow pigment) bilirubin degraded in liver if liver is damaged, no breakdown of bilirubin excess bilirubin in blood yellow color jaundice (hepatitis, yellow fever) platelets: function in blood clotting mechanism 10 Acquired Immunity Cells of the Immune System leukocytes: WBCs phagocytes - ingest foreign matter PMNs - polymorphonuclear cells - first response blood phagocytes - many lysosomes that contain digestive enzymes - 2 day life span monocytes - blood phagocytes mature into macrophages macrophages - tissue phagocytes can process and present Ag dendritic cells - tissue dwellers main Ag processors and presenters 11 Acquired Immunity Cells of the Immune System leukocytes: WBCs lymphocytes - specific immune response B lymphocytes humoral immunity antibody production T lymphocytes immune response regulation cellular immunity 12 Acquired Immunity Tissues of the Immune System The Lymphatic System lymph: fluid that surrounds tissue cells and fills intercellular spaces contains fewer proteins than serum lymphatic system: composed of vessels that circulate lymph 13 Acquired Immunity Tissues of the Immune System The Lymphatic System lymph nodes: pockets of lymphatic tissue located along lymph vessels contain phagocytes and lymphocytes can become enlarged during infection (swollen glands) specialized nodes include tonsils, adenoids, spleen, Peyer's patch, appendix 14 Acquired Immunity Development of Immune System Specificity Development of Immune System Specificity Immune System: series of cells, factors, and processes that provide a specific adaptive response to Ag specificity is dependent on lymphocytes T-lymphocytes cellular immunity B-lymphocytes humoral immunity 15 Acquired Immunity Development of Immune System Specificity Lymphocyte Maturation B cells T cells Bone marrow Release of immature Lymphocytes Maturation in separate sites Thymus Addition of cell receptors Ab primordial stem cells arise in marrow differentiate into either erythropoietic (RBCs, phagocytes) or lymphopoietic cells Bone marrow T cells mature in thymus B cells mature in bursa (birds) or bone marrow Elimination of self-reactive cells Migration to lymph nodes TCR B cell T cell Lymph node 16 Acquired Immunity Development of Immune System Specificity Lymphocyte Maturation B cells T cells Bone marrow Release of immature Lymphocytes Maturation in separate sites Thymus Addition of cell receptors Ab antigen-specific receptors appear on each cell type during maturation allows specific recognition and binding to Ag (lock and key fit) Bone marrow receptor is present even if person unexposed to the Ag (contained in genetic information) B cell receptor is antibody T cell receptor is TCR B cell Elimination of self-reactive cells Migration to lymph nodes T cell TCR Lymph node 17 Acquired Immunity Development of Immune System Specificity Lymphocyte Maturation B cells T cells Bone marrow Release of immature Lymphocytes Maturation in separate sites Thymus Addition of cell receptors Ab lymphocytes with Ag receptors that bind to "self" Ag are eliminated lymphocytes with Ag receptors that do not bind to "self" Ag have potential to bind to microbe Ag both types of cells Bone marrow enter circulation colonize nodes and other lymphatic organs B cell Elimination of self-reactive cells Migration to lymph nodes T cell TCR Lymph node 18 Acquired Immunity Operation of the Immune System Operation of the Immune System 1. entry of antigens to lymphatic or cardiovascular system Foreign microbes 1 2. Ag is phagocytosed by dendritic cells, macrophages and monocytes (antigen-presenting cells) 2 Antigen-presenting cell (APC) 19 Acquired Immunity Operation of the Immune System Operation of the Immune System 3. Ag is processed Foreign of microbes 1 majority Ag is digested epitopes are preserved by phagocytes 2 3 Processed Ag (epitope) MHC epitopes are displayed on surface of APC unprocessed Ag is a poor stimulator of immune system Antigen-presenting cell (APC) 20 Acquired Immunity Operation of the Immune System Operation of the Immune System 2 1 Antigen-presenting cell (APC) 4. epitopes are presented to T helper cells 3 interaction between APC receptor, epitope and specific TCR on T cell surface TCR 4 T helper cell APC MHC epitope TCR T helper cell CD4 21 Acquired Immunity Operation of the Immune System Operation of the Immune System 2 1 Antigen-presenting cell (APC) 5. T helper cells become activated 3 T cells divide form clone of activated T helper cells all have same TCR TCR 4 T helper cell 5 Activated T helper clones 22 Acquired Immunity Regulation by T cells Regulation of the Immune Response Cytokines Helper T cells are regulatory cells required for both cellular and humoral immunity produce cytokines Cytokines B cell communication proteins have effects on other types of WBCs APC Cytokines TC cell TH cell Memory T cell Macrophage 23 Acquired Immunity Regulation by T cells Regulation of the Immune Response Cytokines cytokine functions: assist response of B cells to Ags assist response of cytotoxic T cells (killer T cells) increase killing by phagocytes (increase phagocytosis) APC Cytokines B cell in AIDS Cytokines TC cell helper T cell numbers are depressed suppressed immune system TH cell Memory T cell Macrophage 24 Acquired Immunity Regulation by T cells Regulation of the Immune Response Cytokines some activated T cells form memory T cells If Ag reappears memory T cells produce cytokines quickly one reason for long-lasting immunity APC Cytokines B cell Cytokines TC cell TH cell Memory T cell Macrophage 25 Acquired Immunity Humoral Immunity Humoral Immunity Microbe TH cell humoral immunity: interaction between Ab and Ag in blood (humor refers to blood) 1. circulating Ag binds to specific Ab on B cell surface 2. T helper cells provide cytokine activation signal 5 Memory B cells 2 1 B cell Cytokines 3 plasma cells 4 antibodies Microbes 26 Acquired Immunity Humoral Immunity Humoral Immunity Microbe TH cell 3. activated B cells multiply 2 1 B cell Cytokines form clone of plasma cells produce Ab (a.k.a. immunoglobulin) all have same specificity 5 3 plasma cells 4. plasma cells make Ab for 4-5 days 2000 Ab molecules/second all have same specificity Memory B cells 4 antibodies Microbes 27 Acquired Immunity Humoral Immunity Humoral Immunity Microbe TH cell 5. some activated B cells become memory B cells 2 1 B cell Cytokines remain in lymphoid tissue for 20 or more years when Ag reappears they revert to plasma cells which rapidly produce Ab 5 3 plasma cells flood blood with Ab within hours Memory B cells 4 antibodies Microbes 28 Acquired Immunity Secondary Response Secondary (anamnestic) response Total Antibody Titer Primary response Second exposure to Ag IgG First exposure to Ag Latent period (7-10 days) Total IgG IgM Variable time interval Hours IgM Naive B cells IgM IgM IgG Memory B cells IgG Time 29 Acquired Immunity Humoral Immunity Structure and Type of Antibodies epitope-binding region 2 identical arms (Fab) unique specificity hinge binds to epitopes constant region (Fc) binds to receptors on APCs epitopes flexible hinge permits cross-linking antigens Constant region 5 types identified 30 Acquired Immunity Humoral Immunity IgG IgA IgM IgD IgE Monomer Number of Antigen Binding Sites Molecular Weight Percent of Total Antibody in Serum 2 150,000 80% 23 Yes Dimer, Monomer 4 2 Pentamer 10 900,000 6% 5 No Monomer 2 180,000 1% 3 No Monomer 2 200,000 0.002% 2.5 No 170,000-385,000 13% 6 No Average Life in Serum (Days) Crosses Placenta Fixes Complement Fc Binds to: Biological Function Yes Phagocytes No No No No Mast Cells and Basophils Memory antibody, Secretory antibody: long-term immunity; respiratory and GI maternal antibody tract, tears, saliva, colostrum Primary response antibody Regulatory antibody Antibody of allergy, worm infections 31 Acquired Immunity Humoral Immunity Antigen-Antibody Interactions Ab must react with Ag in such a way that Ag is altered death of microbe inactivation of Ag increased susceptibility to other body defenses 32 Acquired Immunity Humoral Immunity Antigen-Antibody Interactions Opsonization neutralizins bind to receptors on viruses bind to toxins (antitoxins) bacteriolysins damage bacterial membranes agglutinins bind to large particles, cause clumping opsonins enhance phagocytosis (bind to Fc receptor on phagocyte) Neutralization Agglutination Bacterial Lysis 33 Acquired Immunity Cellular Immunity Cellular Immunity (cell-mediated immunity) form of immunity arising from T cells as effectors important defense against: viruses, rickettsia, and bacteria that live within body cells fungi, protozoa, and cancer cells 34 Acquired Immunity Cellular Immunity TCR 1 Infected cell (target cell) Cellular Immunity TC cell epitope 1. T cytotoxic cell binds to target Cytokines 2 All cells express epitopes of cellular proteins Infected cells also express epitopes of infecting agent TH cell TCR binds to foreign epitope 3 Perforin 4 CTLs 6 Granzymes 5 Memory TC cell Lysed cell 35 Acquired Immunity Cellular Immunity TCR 1 Infected cell (target cell) Cellular Immunity TC cell epitope 2. T helper cells provide cytokine signal to activate TC cell Cytokines 2 TH cell 3 Perforin 4 CTLs 6 Granzymes 5 Memory TC cell Lysed cell 36 Acquired Immunity Cellular Immunity TCR 1 Infected cell (target cell) Cellular Immunity TC cell epitope 3. Activated T cytotoxic cells multiply Cytokines 2 Form clone of activated CTL (cytotoxic T lymphocytes) All have same specificity Seek out target cells TH cell 3 Perforin 4 CTLs 6 Granzymes 5 Memory TC cell Lysed cell 37 Acquired Immunity Cellular Immunity TCR 1 Infected cell (target cell) Cellular Immunity TC cell epitope 4. CTLs recognize and bind to Ag-bearing target cells Cytokines 2 release perforin release granzymes TH cell 3 Perforin 4 CTLs 6 Granzymes 5 Memory TC cell Lysed cell 38 Acquired Immunity Cellular Immunity TCR 1 Infected cell (target cell) Cellular Immunity TC cell epitope 5. Perforin inserts in target cell membrane Cytokines 2 Perforates cell membrane Target cell undergoes programmed cell death TH cell 3 Perforin 4 CTLs 6 Granzymes 5 Memory TC cell Lysed cell 39 Acquired Immunity Cellular Immunity TCR 1 Infected cell (target cell) Cellular Immunity TC cell epitope 6. Some activated T cells form memory T cells Cytokines 2 If Ag reappears memory T cells reproduce quickly TH cell provide long-lived cellular immunity CTLs 6 3 Perforin 4 Granzymes 5 Memory TC cell Lysed cell 40
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