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Specific Host Defenses: The Immune Response SECOND LINE A. Cells 1. Phagocytic Cells (neutrophils and macrophages) 2. Natural Killer Cells a. recognize body cells infected with foreign bodies (i.e. viruses) b. utilize perforins  "holeforming" proteins Credit: © Dr. Richard Kessel & Dr. Gene Shih/Visuals Unlimited This phagocyte or macrophage is able to ingest small particles that might be inhaled into the lungs. SEM X1630. 171125 Credit: © Science VU/W.J. Johnson/Visuals Unlimited A macrophage shown engulfing cancer cells. Macrophage cells circulate through the blood stream searching for bacteria, dead or abnormal cells, or foreign objects to engulf. SEM X3000. 228399  B. Antimicrobial Proteins Cytokines- reg. intensity/duration of immune response  Interferons - produced by viral infected cells, inhibits viral replication  Interleukins - secreted by macrophages, lymphocytes; resets thermostat Chemokines -attract and direct movement of immune sys. Cells Tumor Necrosis Factors attacks tumors Inflammatory Response –  1. HISTAMINE release…. -histamine makes capillary walls leaky, relaxes smooth muscle  blood flows into wounded area: inflammation …increased delivery of WBCs, etc.  2. Clotting response - chemically stimulated by wounded cells (platelets, etc.) 3. Attraction of Phagocytic WBCs (i.e. Macrophage) / pus  C. 4. Fever elevated temperature... - inhibits bacteria metabolism - stimulates phagocytic WBCs - increases production of interferon in viral attacks aspirin reduces fever; prolongs viral (flu) infections Complement system  group of proteins that aid in immune response functions include a) lysis b) coating pathogens to make them easier to catch c) attract white blood cells – “chemotaxis” d) stimulate immune response Innate or Genetic Immunity: Genetically determined. May be due to lack of receptors or other molecules required for infection. Immunity of mice to poliovirus. Acquired Immunity:Immunity that an organism develops during lifetime. ACQUIRED – ADAPTIVE IMMUNITY - ANTIGEN PRESENTATION IS A KEY CONCEPT!!!! - APC (ANTI-PRESCELLS) T Cells and Cell Mediated Immunity Cellular Components of Immunity: T cells are key cellular component of immunity. T cells have an antigen receptor that recognizes and reacts to a specific antigen (T cell receptor). T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells. MHC Class I: Found on all cells. MHC Class II: Found on phagocytes. Clonal selection increases number of T cells. T Cells Only Recognize Antigen Associated with MHC Molecules on Cell Surfaces T Cells and Cell Mediated Immunity 1. T Helper (TH) Cells: Central role in immune response. + Most are CD4 Recognize antigen on the surface of antigen presenting cells (e.g.: macrophage). Activate macrophages Induce formation of cytotoxic T cells Stimulate B cells to produce antibodies. Types of T cells (Continued) 2. Cytotoxic T (Tc) Cells: Destroy target cells. Recognize antigens on the surface of all cells: •Kill host cells that are infected with viruses or bacteria. •Recognize and kill cancer cells, transplanted tissue. Release protein called perforin which causing lysis of infected cells. Undergo apoptosis when stimulating antigen is gone. Credit: © Dr. Dennis Kunkel/Visuals Unlimited Human T-lymphocyte attacking fibroblast tumor/cancer cells. SEM X500. 284555 Credit: © Science VU/Visuals Unlimited Cancer cell with several T-lymphocytes attacking it. 300609 Credit: © Science VU/Visuals Unlimited Two dead cancer cells, their cell walls and bodies disintegrating after a successful Tlymphocyte attack. 300636 Types of T cells (Continued) 3. Delayed Hypersensitivity T (TD) Cells: Mostly T helper and a few cytotoxic T cells that are involved in some allergic reactions (poison ivy) and rejection of transplanted tissue. 4. T Suppressor (Ts) Cells: May shut down immune response. Immune system is an example of positive feedback system enhances a runaway effect TH activation by MHC II releases interleukins which stimulates B cells and other T cells interleukins stimulates activity of TH cells TH cell stimulates B cells specific for antigen to become plasma cells. Antigens are mainly proteins on viruses, bacteria, foreign red blood cells… Duality of Immune System I. Humoral (Antibody-Mediated) Immunity Involves production of antibodies against foreign antigens. Antibodies are prod. by type of lymphocytes called B cells. B cells stim. will secrete antibodies called plasma cells. Antibodies are found in ECF (blood plasma, lymph, mucus, etc.) and the surface of B cells. Defense against pathogen/toxins before they enter cells. Also cause certain reactions against transplanted tissue. Antibodies Proteins that recognize and bind to a particular antigen with very high specificity. Made in resp. to exp. to antigen. One virus or microbe may have several antigenic determinant sites, to which different antibodies may bind. GENERATING ANTIBODY DIVERSITY – 3 mechanisms 1) Genomic Rearrangement (during differentiation) 2) Insertions/Deletions when “pasted” together 3) Hypermutation – up to 10,000 times higher than normal STEM CELL DNA FOR ANTIBODY PRODUCTION How Do B Cells Prod. Antibodies? Clonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells, which actively secrete antibodies. Each B cell produces antibodies that will recognize only one antigenic determinant. Humoral Immunity (Continued) Apoptosis Programmed cell death (“Falling away”). Human body makes 100 million lymphocytes every day. If an equivalent number doesn’t die, will develop leukemia. Duality of Immune System…. II. Cell Mediated Immunity specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues: Helper T cells Cytotoxic T cells T cells regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc. Clonal Deletion: B and T cells that react against self antigens appear to be destroyed during fetal development. Process is poorly understood. Immunological Memory Primary Response: After initial exposure to antigen, no antibodies are found for several days. Most B cells become plasma cells, some memory cells. Gradual decline of antibodies Secondary Response: Subsequent exposure to the same antigen displays a faster and more intense antibody response. Increased antibody response is due to the existence of memory cells, which rapidly produce plasma cells upon antigen stimulation.  AUTOIMMUNITY  Lupus - immune response to your own cells parts (especially nucleic acids)  rheumatoid arthritis - immune response to joint cartilage  insulin-dependant diabetes – attacks beta cells of pancreas  multiple sclerosis - attack myelin sheath  Allergic Response -over-reaction to a harmless substance  response is caused by histamine • tissue swelling , excess mucous (yum) • constricted airway poss. Anaphylatic shock • sneezing • tears Rh Blood Group and Pregnancy Rh – mother can produce antibodies to Rh + child Immune system can attack Rh+ child (2nd pregnancy) Potential PATHOGENS - bacteria, viruses, parasites Prions can cause Bovine Spongiform Encephalopathy: “Mad Cow Disease”  cause by a protein! KURU  AIDS  HIV attacks TH cells  some cells are killed by immune system but others produce more virus  immune system slowly loses Credit: © Dr. Hans Gelderblom/Visuals Unlimited HIV (Human Immunodeficiency Virus) budding. HIV infects a number of cells in the body, though the main target is a lymphocyte cell, which is a type of T-cell. Once the HIV virus has infected the host cell it then replicates itself with thousands of copies. TEM X120,000. 203226
 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
									 
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                             
                                            