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Immunity
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Impacts, Issues Frankie’s Last Wish
Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers – including the one that killed Frankie McCullogh
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A. Integrated Responses to Threats
Immunity - the capacity to resist and combat infection by pathogens such as viruses, bacteria, and fungi Proteins in eukaryotic cell membranes have unique patterns (antigens) that the body recognizes as self & cells of multicelled eukaryotes have receptors that recognize nonself cues (anitgens) on or in pathogens, and trigger defense responses
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B. Three Lines of Defense
1. Physical, chemical, and mechanical barriers - keep pathogens outside the body
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Chemical Weapons of Immunity
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Vertebrate Surface Barriers
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B. Three Lines of Defense
1. Physical, chemical, and mechanical barriers - keep pathogens outside the body 2. Innate immunity General responses destroy invaders inside the body before they become established Complement: Proteins that destroy microorganisms or flag them for phagocytosis
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Animation: Innate defenses
videos_animations/innate_defenses_m.html
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B. Three Lines of Defense
1. Physical, chemical, and mechanical barriers - keep pathogens outside the body 2. Innate immunity General responses destroy invaders inside the body before they become established Complement: Proteins that destroy microorganisms or flag them for phagocytosis 3. Adaptive immunity system of defenses that specifically targets billions of different antigens an individual may encounter during its lifetime Huge populations of white blood cells form to target and remember a specific antigen
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Comparing Innate and Active Immunity
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White Blood Cells
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C. Innate Immune Responses
Innate immune mechanisms nonspecifically eliminate pathogens that invade internal tissues before they become established Phagocytes Complement Inflammation Fever
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1. Phagocytes (Macrophages)
Large phagocytes that patrol interstitial fluid and engulf and digest pathogens Secrete cytokines when receptors bind to antigen Cytokines attract more macrophages, neutrophils, and dendritic cells to infection site
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Complement proteins become activated when they encounter antigen
Cascading enzyme reactions concentrate activated complement at infection site Complement attracts phagocytes to infection site and tags pathogens for destruction Forms attack complexes that puncture bacteria Helps mediate active immunity
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Complement Attack Complexes
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Animation: Complement proteins
videos_animations/membrane_attack.html
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Inflammation A local response to tissue damage characterized by redness, warmth, swelling and pain, triggered by activated complement and cytokines Mast cells release histamine, increasing capillary permeability Phagocytes and plasma proteins leak out, attack invaders, form clots, and clean up debris
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A Bacteria invade a tissue and release toxins or metabolic products that damage tissue.
D Complement proteins attack bacteria. Clotting factors also wall off inflamed area. E Neutrophils and macrophages engulf invaders and debris. Macrophage secretions kill bacteria, attract more lymphocytes, and initiate fever. B Mast cells in tissue release histamine, which widens arterioles (causing redness and warmth) and increases capillary permeability. C Fluid and plasma proteins leak out of capillaries; localized edema (tissue swelling) and pain result. Figure 38.8 Inflammation in response to bacterial infection. Above, in this example, white blood cells and plasma proteins enter a damaged tissue. Right, the micrograph shows a phagocyte squeezing through a blood vessel wall. Stepped Art Fig. 38-8, p. 665
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Fever A temporary rise in body temperature – above the normal 37°C (98.6°F) – that often occurs in response to infection Cytokines stimulate brain cells to release prostaglandins, which act on the hypothalamus Fever enhances the immune response by speeding up metabolism and phagocyte activity Fever over 40.6°C (105°F) can be dangerous
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D. Overview of Adaptive Immunity
Vertebrate adaptive immunity adapts to different antigens it encounters during its lifetime Lymphocytes and phagocytes interact to effect four defining characteristics: Self/nonself recognition, specificity, diversity, and memory
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3. First Step – The Antigen Alert
Once a B or T cell recognizes and binds to a specific antigen, it begins to divide by mitosis - all descendent cells recognize the same antigen T cells do not recognize an antigen unless it is presented by an antigen-presenting cell - macrophages, B cells, and dendritic cells digest particles and display antigen-MHC complexes
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c. Cell Types Effector cells - differentiated lymphocytes (B and T cells) that act at once to fight infection Memory cells - long-lived B and T cells reserved for future encounters with the same antigen
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cell engulfs an antigen-bearing particle
antigen–MHC complexes become displayed on cell surface endocytic vesicle forms MHC markers bind fragments of particle particle is digested into bits lysosome fuses with endocytic vesicle Figure 38.9 Antigen processing. (a) A macrophage ingests a foreign cell. (b) From encounter to display, what happens when a B cell, macrophage, or dendritic cell engulfs an antigenic particle—in this case, a bacterium. These cells engulf, process, and then display antigen bound to MHC markers. The displayed antigen is presented to T cells. Stepped Art Fig. 38-9b, p. 666
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4. Two Arms of Adaptive Immunity
Antibody-mediated immune response - B cells produce antibodies that bind to specific antigen particles in blood or interstitial fluid Cell-mediated immune response - Cytotoxic T cells and NK cells detect and destroy infected or altered body cells
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Interactions Between Antibody-Mediated and Cell-Mediated Responses
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5. Intercepting and Clearing Out Antigen
After engulfing antigen-bearing particles, dendritic cells or macrophages migrate to lymph nodes, where T cells bind and initiate responses During an infection, lymph nodes swell due to accumulation of T cells Antibody-antigen complexes bound by complement are cleared by the liver and spleen
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The Lymphatic System
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E. Antibodies and Other Antigen Receptors
Antigen receptors on B and T cells have the potential to recognize billions of different antigens Antibody Y-shaped antigen receptor (protein), made only by B cells, that binds only to the antigen that prompted its synthesis Activates complement, facilitates phagocytosis, or neutralizes pathogens or toxins
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Antibody Structure
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3. Making Antigen Receptors
Genes that encode antigen receptors occur in several segments on different chromosomes Different versions are randomly spliced together during B or T cell differentiation, producing about 2.5 billion different combinations T cells mature in the thymus, which stimulates production of MHC and T cell receptors
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Antigen Receptor Diversity
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F. The Antibody-Mediated Immune Response
Antigen activates naïve B cells and dendritic cells Naïve T cell binds to APC and differentiates into effector and memory helper T cells Helper T cells bind antigen-MHC complexes on activated B cell and secrete cytokines B cell differentiates into effector B cells, which produce antibodies targeting a specific antigen, and memory B cells
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antigen- presenting dendritic cell
B bacterium antigen- presenting dendritic cell B The dendritic cell engulfs the same kind of bacterium that the B cell encountered. A naive B cell B cell complement A The B cell receptors on a naïve B cell bind to a specific antigen on the surface of a bacterium C The antigen-MHC complexes on the antigen-presenting cell are recognized by antigen receptors on a naïve T cell. naive T cell effector helper T cell memory helper T cell C D cytokines D Antigen receptors of one of the effector helper T cells bind antigen-MHC complexes on the B cell. E memory B cell effector B cell E The cytokines induce the B cell to divide, giving rise to many identical B cells. F F The effector B cells begin making and secreting huge numbers of IgA, IgG, or IgE. Figure 38.14 Example of an antibody-mediated immune response. Stepped Art Fig , p. 670
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5. Clonal Selection and Memory Cells
Only B cells with receptors that bind antigen divide (clone) and differentiate into effector and memory B cells First exposure (primary response) produces memory B and T cells; secondary response is stronger and faster
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Clonal Selection and Memory Cells
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Primary and Secondary Immune Response
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G. The Cell-Mediated Response
Dendritic cell ingests altered body cell, displays antigen-MHC complexes, migrates to lymph node Naïve helper T and cytotoxic T cells bind to APC Activated helper T divides and differentiates into memory and effector cells; cytokines signal division of activated cytotoxic T cells Cytotoxic T cells circulate and touch-kill altered body cells
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A A dendritic cell engulfs a virus-infected cell.
antigen- presenting dendritic cell A A dendritic cell engulfs a virus-infected cell. B effector helper T cell memory helper T cell B Receptors on a naïve helper T cell bind to antigen-MHC complexes on the dendritic cell. naive helper T cell naive cytotoxic T cell C activated cytotoxic T cell C Receptors on a naïve cytotoxic T cell bind to the antigen-MHC complexes on the surface of the dendritic cell. D cytokines memory cytotoxic T cell effector cytotoxic T cell D The activated cytotoxic T cell recognizes cytokines secreted by the effector helper T cells as signals to divide. Figure 38.17 Example of a primary cell-mediated immune response. Figure It Out: What do the large red spots represent? Answer: Viruses E E The new cytotoxic T cells circulate through the body. Stepped Art Fig , p. 672
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Cytotoxic T Cells
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Animation: Cell mediated response
videos_animations/cell_mediated_vid.html
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5. Natural Killer Cells Cytokines secreted by helper T cells also stimulate natural killer (NK) cell division Unlike cytotoxic T cells, NK cells can kill infected cells that are missing all or part of their MHC markers
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H. Allergies An immune response to a typically harmless substance (allergen) First exposure stimulates production of IgE, which becomes anchored to mast cells and basophil Later exposure stimulates secretion of histamine and cytokines that initiate inflammation Anaphylactic shock is a severe and potentially fatal allergic reaction
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Allergies: Annoying or Life-Threatening
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ABC video: Food Allergy Increase
videos_animations/Food_Allergy_Increase.html
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I. Vaccines Immunization - the administration of an antigen-bearing vaccine designed to elicit immunity to a specific disease Vaccine (active immunization) - a preparation containing an antigen that elicits a primary immune response Passive immunization - administration of antibodies; no immune response
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Smallpox Vaccine Edward Jenner created the first vaccine against smallpox, which has now been eradicated
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Recommended Immunizations
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J. Immunity Gone Wrong Misdirected or compromised immunity is sometimes the result of mutation or environmental factors The outcome is often severe or lethal
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1. Autoimmune Disorders Sometimes lymphocytes and antibodies fail to discriminate between self and nonself Autoimmune response An immune response that is misdirected against the person’s own tissues Rheumatoid arthritis, Graves’ disease, multiple sclerosis
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2. Immunodeficiency In immunodeficiency, the immune response is insufficient to protect a person from disease Primary immune deficiencies are present at birth - SCIDs, ADA Secondary immune deficiency results from exposure to an outside agent, such as a virus - AIDS
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3. Gene Therapy Primary immunodeficiency is the result of mutation; Cindy Cutshwall was successfully treated for ADA, a type of severe combined immunodeficiency (SCID), using gene therapy
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Video: Gene therapy videos_animations/gene_therapy.html
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K. AIDS Revisited—Immunity Lost
Acquired immune deficiency syndrome (AIDS) A group of disorders resulting from a failure of the immune system due to HIV infection Includes rare cancers and infections caused by normally harmless microorganisms Human immunodeficiency virus (HIV) - a retrovirus that attacks specific cells of the immune system, including helper T cells
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T Cells and AIDS
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Global HIV and AIDS Cases
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3. Transmission and Treatment
Common modes of HIV transmission - unprotected sex, mother to child, shared syringes HIV testing - antibodies are found in blood, saliva or urine Drugs - there is no cure; protease inhibitors and reverse transcriptase inhibitors can slow its progress
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4. Prevention Vaccines - experimental vaccines are mostly ineffective or risky; the virus’ high mutation rate is an obstacle Education - the best option for preventing the spread of HIV is teaching people how to avoid being infected
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5. The Global AIDS Program
The global battle continues; researchers are using several strategies to develop an HIV vaccine
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Video: HPV vaccine videos_animations/csHPV_Vaccine.html
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