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Figure 43.0 Specialized lymphocytes attacking a cancer cell The Body’s Defense: The Immune System 1 A lymphocyte: They display specificity for an antigen There are: B lymphocytes or cells and T lymphocytes or cells They display: Specificity Diversity Memory Can distinguish self from nonself 2 Figure 43.1 An overview of the body's defenses 3 Nonspecific Defenses 1. Skin a) Oil and sweat glands keep pH about 3-5 and this prevents bacteria from inhabiting the area. b) Lysozyme: an example of a protein that digests bacterial cell walls. Found in eyes, upper respiratory tract. 2. Mucous a) traps bacteria in respir. tract b) action of cilia 4 3. Action of neutrophils a) phagocytes b) exhibit a chemotaxis: attracted by chemicals released by damaged cells 4. Monocytes a) develop into macrophages that will engulf bacteria b) attracted to the polysaccharides on the bacteria’s surface. c) engulfed into a vacuole and then nitric oxide (NO) will destroy it. 5. Natural Killer Cells a) attack virus-infected cells and cause the cells to lyse 5 Figure 43.3 Phagocytosis by a macrophage Bacteria are the rodshaped structures 6 Figure 43.3x Macrophage 7 The Importance of the Lymph Nodes 8 The Inflammatory Response Pyrogens Complement system: bunches of proteins Interferons: released by virus-infected cells 9 Figure 43.6 Clonal selection Selected B cell makes clones Antigen receptors are actually membrane antibodies or immunoglobulins 10 Immune Response: Know this well Primary Immune Response 11 Figure 43.10 An overview of the immune responses (Layer 2) 12 Figure 43.8 The development B and T Cells or lymphocytes 13 Figure 43.9 The interaction of T cells with MHC molecules 14 Major Histocompatibility Complex (MHC) 1. There are genes that code for two types of distinguishing glycoproteins on a cell’s surface: a) Class I MHC b) Class II MHC 15 2. The Role of the MHC Glycoproteins a) Antigen Presentation 16 Figure 43.10 An overview of the immune responses (Layer 4) 17 Figure 43.11 The central role of helper T cells: a closer look TH cells: involved in both cell mediated and humoral responses. CD4: Helper T cell surface protein: binds to the presented antigen fragment of the APC Upon activation by the APC, the TH cells will make many clones and also produce memory TH cells. Once activated, a macrophage will make IL-1 which helps to make IL-2 which stimulates TH cells to divide as well as the 18 production of B cells Figure 43.12a The functioning of cytotoxic T cells MHC I Glycoprotein: all nucleated cells Tumor Cells: present tumor antigens to Tc cells so the body can fight against tumors 19 Figure 43.12b A cytotoxic T cell has lysed a cancer cell 20 Figure 43.13 Humoral response to a T-dependent antigen (Layer 3) B cells can be stimulated by TH cells to make antibodies. This is a T- dependent antigen. 21 Figure 43.10 An overview of the immune responses (Layer 2) 22 Figure 43.11 The central role of helper T cells: a closer look TH cells: involved in both cell mediated and humoral responses. CD4: Helper T cell surface protein: binds to the presented antigen fragment of the APC Upon activation by the APC, the TH cells will make many clones and also produce memory TH cells. Once activated, a macrophage will make IL-1 which helps to make IL-2 which stimulates TH cells to divide as well as the 23 production of B cells Epitopes (antigenic determinants) Epitopes: small portion of an antigen to which the antibody binds. Epitope B Epitope C Epitope A 24 Figure 43.15a,b The structure of a typical antibody molecule 25 Fig. 43-13 DNA of undifferentiated B cell V37 V38 V39 V40 J1 J2 J3 J4 J5 Intron C 1 DNA deleted between randomly selected V and J segments DNA of differentiated B cell V37 V38 V39 J5 Intron C Recombinase acts randomly to combine any one of the J gene segments with any one of the V gene segments. Functional gene 2 Transcription pre-mRNA V39 J5 C Intron 3 RNA processing mRNA Cap V39 J5 C 40V x 5J x 1C = 200 different ways. B cell receptor Poly-A tail V V V 4 Translation V C C Light-chain polypeptide V Variable region C C Constant region B cell C Figure 43.15c Antibody molecule 27 Table 43.1 The Five Classes of Immunoglobulins 28 Figure 43.16 Effector mechanisms of humoral immunity 29 Figure 43.17 The classical complement pathway, resulting in lysis of a target cell 30 Types of Immunity 1. Active Immunity a) naturally acquired after an infection (chicken pox) b) acquired by an immunization (vaccination) c) person demonstrates the secondary response 2. Passive Immunity a) antibodies acquired from another person b) antibodies are passed from a mother’s breast milk to nursing child while the child’s immune system is developing. c) a rabies bitten person can receive antibodies from those vaccinated against rabies 31 Allergic Reactions 1. An allergen causes a specific kind of antibody IgE to be released from plasma cells and instead of binding to the allergen (pollen) they bind to mast cells that are present in connective tissue (ligaments, tendons, etc). 2. This causes the mast cells to release histamine 3. Histamine causes blood vessels to dilate and also increases their permeability so lots of fluid leaks out. 4. Antihistamine 5. Anaphylactic shock: allergic response is one of huge release of histamine and so much blood goes to periphery that blood pressure drops. (bee stings, food allergies (peanuts) 32 Person takes a shot of epinephrine. Figure 43.18 Mast cells, IgE, and the allergic response 33 Figure 43.x4 Alternaria spores, a cause of allergies in humans 34 Figure 43.19 A T cell infected with HIV T cell Viruses: small blue dots 35 Figure 43.19x2 HIV budding 36 Figure 43.19x2a T cell infected with HIV 37 Figure 43.20 The stages of HIV infection 38 HIV MOLECULAR BIOLOGY 1. Retrovirus 2. Several strains of HIV 3. Binding and Entry a) RNA has 9 different genes encoding 15 proteins. b) Entry requires the fusion of the viral envelope with the host cell membrane. c) The viral envelope interacts with specfic cell surface receptors. d) gp120 is on the viral surface binds to the CD4 receptors on the T cells. e) gp41 4. Virus attacks cells with CD4 receptors on TH cells(immune system cells) 5. Role of TH cells? Stimulates the immune system; they bind to MHC II APC’s which stimulates both cell mediated immunity and antibody secretion from plasma cells 39 6. HIV binds to probably several proteins: CD4 receptor, a fusin protein which allows for the envelope of the virus to join with the T cell and another receptor CCR5 which is on macrophages. 7. 8. CXCR4 binds to T-cells in later stages of the disease. In up to 13% of individualos of northern Eurpean descent, a naturally occurring deletion of 32 base pairs in the CCR5 gene results in a mutant CCR5 receptor that never reaches the cell surface. a) 9. 10. Individuals homozygous for this mutation (1-2% of Caucasian population) are almost completely resistant to HIV infection. Binding of gp120 and CD4 produces changes in gp41, it springs open and grabs the lipid bilayer of the target cell. This promotes fusion. Detection for HIV antibodies: 1-12 months after exposure/infection. 40