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  1. 1. CHAPTER 24 The Immune System The Continuing Problem of HIV First identified in 1981 in US Epidemic throughout the world 14K infected each day 900K in US with HIV infection today Attacks immune system Main defense against infectious diseases/cancer Enters cells of immune system Testing positive for HIV not the same as having AIDS May take 10 years for AIDS to develop The Continuing Problem of HIV, cont. AIDS virus transmitted mainly in blood and semen Enters body thru small wound during sexual contact Via needles contaminated w/infected blood Screening of blood at blood banks greatly reduced risk from transfusion borne virus Misconceptions Developing countries still believe just from drug addicts/homosexuals Increase in cases in heterosexuals w/o hx of drugs Includes teens and college students The Continuing Problem of HIV, cont. AIDS Demonstrates how much we depend on body’s built-in defense system Immune system Very specific defense system Recognizes invader Produces large numbers/cells to combat that PARTICULAR agent Healthy individuals Specific defense backs up several mechanisms of Nonspecific resistance Provides non-discriminating protection against variety of invaders
  2. 2. NONSPECIFIC DEFENSES AGAINST INFECTION Nonspecific defenses against infections include the skin/mucous membranes, phagocytic cells, and antimicrobial proteins Body’s first line/defense Don’t distinguish one infectious agent from another Skin Major player in nonspecific defense Outer layer Tough barrier of dead cells impenetrable to most bacteria/viruses Acids from skin glands inhibit microbial growth Sweat, saliva, tears Contain lysozyme Enzyme that attacks cell walls of many bacteria NONSPECIFIC DEFENSES AGAINST INFECTION, cont. Mucous membranes Protect tissues open to external environment Digestive/respiratory systems Have other nonspecific defenses Stomach acid-kills most bacteria ingested with food Respiratory system Hairs/nostrils filters air Mucus traps most microbes/dirt Cilia-sweep mucus upward and out of system NONSPECIFIC DEFENSES AGAINST INFECTION, cont. Microbes that do penetrate outer systems Confronted with nonspecific defensive cells Classified as White Blood Cells Found in interstitial fluid and blood vessels Called Phagocytes- Three types Neutrophils Monocytes Both are phagocytic wbc’s Engulf microbes they encounter
  3. 3. NONSPECIFIC DEFENSES AGAINST INFECTION, cont. Macrophages (“big eaters”) Large phagocytic cells Develop from monocytes Wander actively in interstitial fluid/”eating” microbes they encounter Natural Killer Cells Another type of wbc Attack cancer cells/infected body cells, especially those with viruses Other nonspecific defenses Proteins Attack microbes directly/impede their reproduction Interferons Complement proteins NONSPECIFIC DEFENSES AGAINST INFECTION, cont. Interferons Proteins produced by virus-infected cells Help other cells resist viruses How it works Virus infects a cell Turns on interferon genes in cell’s nucleus Causes cell to make interferon-infected cell dies Interferon from infected cell MAY diffuse to healthy cells Stimulates them to produce interferon that inhibits viral reproduction Very nonspecific Confers resistance to unrelated viruses Short term defense NONSPECIFIC DEFENSES AGAINST INFECTION, cont. Interferon’s, cont. Made in small quantities rDNA’s can make large amounts for viral infections MAY be useful in treating certain cancers Complement proteins Circulate inactive in blood plasma Activated by immune system/microbes Some coat microbe surfaces/makes easier for macrophages to engulf Others cut lethal hoes in microbial membranes Amplifies the inflammatory response
  4. 4. NONSPECIFIC DEFENSES AGAINST INFECTION, cont. The inflammatory response mobilizes nonspecific defense forces Major component of nonspecific defense Triggered by damage to tissue-whether microbial or physical Mosquito bite-red and swollen area NONSPECIFIC DEFENSES AGAINST INFECTION, cont. Inflammatory response; chain of events Damaged cells release chemicals such as histamine that signal an “attack” Sparks mobilization of various defenses Histamine-dilates near-by blood vessels so that they become “leaky” Increases blood flow to area Plasma passes out of leaky vessels into interstitial fluid of infected tissue Other chemicals attract phagocytes that squeeze out of blood vessels into interstitial fluid/tissues Causes redness, heat, and swelling NONSPECIFIC DEFENSES AGAINST INFECTION, cont. WBC’s in area engulf bacteria/remains of dead/injured body cells Inflammatory Response also Prevents spread of infection Clotting proteins form small clots Helps seal off infected region Allow repair of damaged tissue to begin Lymphatic System Specific Immunity: 24.4 The immune response counters specific invaders The immune system Provides another line defense in the event that nonspecific defenses fail Recognizes/defends against microbes/cancer cells More effective than nonspecific resistance Also amplifies nonspecific responses Inflammation and complement Must be “primed” by an antigen Responds w/increase in # of cells Attack invader directly Produce defensive proteins Called antibodies Specific for a particular antigen
  5. 5. Specific Immunity: 24.4 The immune response counters specific invaders, cont. Antigen Molecule that elicits an immune response (antigen=antibody-generating) Include certain molecules surfaces of particles such as virus, bacteria, mold spores, cancer cells, pollen, house dust, cell surfaces of transplanted organs Antibody Protein found in blood plasma Attaches to particular kind of antigen Counters its effects Specific Immunity: 24.4 The immune response counters specific invaders, cont. Immune system, cont Extremely specific-has “memory” Remembers antigens encountered previously Reacts against them quicker, with more vigor during subsequent exposure Ex: Rubella Unlike nonspecific defenses, immune response is adaptive; i.e., exposure to a particular foreign agent enhances future response to that same agent Specific Immunity: 24.4 The immune response counters specific invaders, cont. Immunity Resistance to specific invaders Usually acquired by natural infection Also achieved by vaccination Vaccine=harmless variant of a disease-causing microbe Stimulates immune system to produce “memory” of that particular disease Resultant immunity, whether natural/induced called Active Immunity Body stimulate to produce antibodies in its own defense Passive Immunity Antibodies from an outside source-ex: mothers antibodies in fetus Temporary b/c immune system not stimulated by antigens Only effective for few weeks/months
  6. 6. Specific Immunity: 24.5 Lymphocytes mount a dual defense Lymphocytes WBC’s spend most time in tissues/organs of lymphatic system Produce immune response Originate from stem cells in bone marrow Some continue to develop in bone marrow Become B lymphocytes or B CELLS Others carried by blood to thymus Become T lymphocytes or T CELLS Both mount dual defense B cells-secrete antibodies Dissolve in blood; i.e., called Humoral Immunity Defends against bacteria/virus in body fluids Can be passively transferred by injected blood plasma from immune individual into non- immune individual Specific Immunity: 24.5 Lymphocytes mount a dual defense, cont. Lymphocytes, cont T cells Called Cell-mediated immunity Cannot be passively transferred with plasma Only by T cells from one person to another Circulate in blood and lymph Attack body cells infected w/bacteria/virus Work against fungi/protozoa Important in protection against own cells (cancer) Indirectly promote phagocytosis Stimulating B cells to produce antibodies Therefore involved in both cell-mediated and humoral immunity After stimulation, cell synthesizes specific proteins, builds them into plasma membrane, called antigen receptors Specific Immunity: 24.5 Lymphocytes mount a dual defense, cont. Lymphocytes, cont. Antigen receptors Capable binding one specific type antigen B Cell Molecules of particular antibody that B cells will secrete Once in place, recognizes a specific antigen/mounts attack against it B Cell
  7. 7. Specific Immunity: 24.6 Antigens have specific regions where antibodies bind to them Antigens that elicit immune response Usually don’t belong to host Proteins/large polysaccharides surface of viruses/foreign cells Ex: Protein-coat viruses, capsules/cell walls bacteria Identified by localized regions called antigenic determinants on surface of antigen Antigen-binding site identified by complementary shapes, like enzyme/substrate or lock/ key Usually has several different determinants Different antibodies can bind to same antigen Single antigen may stimulate production several distinct antibodies Binding antibodies to antigenic determinants Specific Immunity: 24.7 Clonal selection musters defensive forces against specific antigens Clonal selection-method of immune system to defend against infinite variety of antigens Initial response produces few lymphocytes-selected cells These proliferate, forming a clone specific for that stimulating antigen Clonal selection of B cells Specific Immunity: 24.8 The initial immune response results in a type of “memory” nd In immune system, first exposure elicits effective response, 2 encounter gives a stronger response Primary immune response st 1 exposure Doesn’t start right away Takes several days for lymphocytes to activate to antigen/form clones of effector cells Secondary immune response nd 2 exposure nd 2 exposure to same antigen Higher levels/antibodies produced O Lasts longer than 1 response
  8. 8. Immunological memory Specific Immunity: 24.8 The initial immune response results in a type of “memory”, cont. O O 1 and 2 immune response-cellular events Exposure triggers clonal selection-results in cloned lymphocyte Each genetically identical-2 sets Effector cells Clones fight antigen/secrete antibodies (B cells) Survive short time-few days Memory cells Different in appearance/function Last decades/remain in lymph nodes nd After 2 exposure, multiply quickly into effectors and more memory cells Cellular basis of immunological memory Specific Immunity: 24.9 Overview: B cells are the main warriors of humoral immunity B cells first selected by antigen Surface receptors bind w/antigens Binding triggers growth, division, further differentiation Clones contain many effector B cells=plasma cells Smaller # of memory B cells Plasma cells secrete antibodies-about 2000/sec Contribute to destruction/block harmful effects Computer graphic of a “Y” shaped antibody molecule Antibody structure Antibodies are the weapons of humoral immunity Antibodies mark antigens for elimination 24.13 T cells mount the cell-mediated defense and aid humoral immunity B cell/antibody producing humoral immunity only one part of system Identifies/helps destroy invaders in blood, lymph, or interstitial fluid; i.e., outside cell Intracellular Viruses and others Enter cell Cell-mediated defense of T cells that deals with these B Cells Respond to free antigens present in body fluids T Cells Respond ONLY to antigens present on surface of body’s only cells Two types of T cells 24.13
  9. 9. T cells mount the cell-mediated defense and aid humoral immunity, cont. APCs PRESENTS foreign antigen to helper T cell-Macrophage Macrophage ingests foreign particle/breaks into fragments-foreign antigens Self protein of macrophage bind the foreign antigens Display them on cell’s surface Each has unique set of self proteins Identifies cell as self Helper T cell recognize and bind to the combination of self protein/foreign antigen on APC “Takes two keys to activate system!” T cell receptor Two binding sites One for antigen One for self protein Can only bind to ONE self/non-self complex on an APC 24.13 T cells mount the cell-mediated defense and aid humoral immunity, cont. T cell/non-self complex Example of a signal-transduction pathway Activates T cell itself APC secrets interleukin-1 Stimulates helper T cell T cells mount the cell-mediated defense and aid humoral immunity, cont. What does the helper T cell do? Promote immune response in several ways Most important secretion of other stimulating proteins Interleukin-2/which has 3 major effects Makes helper T cell itself grow/divide, producing both memory cells and more active helper T cells Example of Positive-feedback-amplifies cell-mediated response Interleukin-2 stimulates activity of cytotoxic T cells Helps activate B cells, which stimulates humoral immunity
  10. 10. T cells mount the cell-mediated defense and aid humoral immunity, cont. Cytotoxic T cells Only T cells that kill other cells Target infected body cells When activated Identify infected cells same way as helper T cells Binds to self/non-self complex which initiates signal—transduction-activates T cell to synthesize new protein, including one called perforin Perforin discharged/attaches to infected cell’s membrane and makes holes in it. Another protein enters and trigger process called programmed cell death Infected cell dies and is destroyed 24.15 The immune system depends on our molecular fingerprints Key to immune system is ability to recognize self proteins Everyone’s are unique Two types of self proteins Class I-occur on all nucleated cells Class II-found only on few types of cells B cells, activated T cells, and macrophages 12 different genes determine self proteins Makes it virtually impossible for people to have same proteins Called MHC 24.16 Malfunction of failure of the immune system causes disease Immune system very effective. When not, causes SERIOUS problems Autoimmune diseases When immune system attacks self Systemic lupus erythematosus-B cells make antibodies against many sorts of molecules- including histones Rheumatoid arthritis-damage to bones/cartilage in joints 24.16 Malfunction of failure of the immune system causes disease Immunodeficiency diseases Lack one or more components of immune system Susceptible to infections that would not usually cause problems SCID-severe combined immunodeficiency Rare congenital disease Both T and B cells absent/inactive Must live in protective barriers or receive SUCCESSFUL bone marrow transplants
  11. 11. 24.17 Allergies are overreactions to certain environmental antigens Allergies Abnormal sensitivities to antigens in our environment Caused by allergens Proteins on pollens, pet dander, Occur rapidly Occurs in man parts of body Nasal passages, bronchi, digestive tract, and skin Sneezing, coughing, wheezing 24.17 Allergies are overreactions to certain environmental antigens, cont. Allergies, cont. Two stage reaction sequence Sensitization When person first exposed to allergen B cells make special class of antibody Antibodies attach to receptor proteins of mast cells Normal body cells that produce histamine, which triggers inflammatory response Exposed to same allergen later Binds to antibodies attached to mast cells Causes cells to release histamine, which triggers allergic symptoms