1. Chapter 43 ~ The Body’s Defenses

2. T CELLS.htm

7. Overview Three cooperative lines of defense Defense against pathogens from food, air, water as well as cancerous cells Nonspecific: (innate) –First Line: external –Second Line: internal Inflammation signals its action has been activated Specific: Third Line (acquired) – Immune System –Simultaneous with Second Line of Defense

8. Lines of Defense

9. I NONSPECIFIC DEFENSES.

10. First Line of defense External –Prevents entry of microbes Skin –Physical barrier Mucous membranes-trap; ciliated epithelial cells sweep out mucus and trapped particulate –Trachea Secretions: Chemical defenses: Oil and sweat glands create a low pH (skin 3-5) Normal flora help maintain this low pH Saliva, tears, mucous secretions contain antimicrobial proteins– for example lysozymes Stomach pH—exception is Hepatitis A virus

11. Second Line of Defense First line broken…. 1.Phagocytic white blood cells (leukocytes) 2.Antimicrobial proteins 3. Natural Killer Cells 4. The Inflammatory response

15. 1. Types of Phagocytic White Blood Cells Neutrophils 60-70% WBCs; Enter infected cells Attracted by chemicals released by infected cell engulf and destroy microbes inside infected tissue. Short life span—few days Monocytes 5% WBCs Develop into macrophages Large; Long lived, use pseudopodia Digest microbe Some migrate; some strategically fixed—such as spleen, lymph nodes and tissue Eosinophils 1.5% WBCs; destroy large parasitic invaders (parasitic worms) Position themselves against invader-discharge enzymes

16. Natural killer (NK) cells Don’t attack microbe directly destroy virus-infected body cells & abnormal cells Not phagocytes Attack-cause cell lysis 2. Antimicrobial Proteins 1. Complement Proteins—lysis results 2. Interferons- Produced by virus-infected cells Inhibit viral replication and activate natural killer cells secreted by virus infected cells—limit cell-to-cell infection Reproduced by recombinant DNA—being tested for treatment of viral infections and cancer Other Nonspecific Defenses

17. The Inflammatory Response Occurs upon damage to tissue –Physical injury –Microorganism entry

18. 3.The Inflammatory Response (localized) Tissue injury; release of chemical signals~ most common is histamine (basophils & mast cells): Causing Vasodilation and increased permeability; Prostaglandins released from WBC and damaged tissues –This increases blood flow to injury – Enhances delivery of clotting elements &more phagocyte( cells release chemokines attracts) : The Vasodilation and increased flow of blood causes characteristic reddening.

19. 4- Phagocytosis of pathogens~neutrophils arrive first, followed by macrophages Macrophages destroy as well as clean up (pus)

20. Systemic Responses to more severe infection Meningitis, appendicitis Fever & Pyrogens: leukocyte-released molecules (pyrogens) increase body temperature—sets body’s thermostat at higher temp. High Temp: inhibits microbe growth; facilitate phagocytosis; speed up tissue repair Septic Shock Overwhelming systemic response High fever & low blood pressure Most common cause of death in U.S. non-coronary critical care units

21. II SPECIFIC IMMUNITY.

22. Specific Immunity—Acquired Immunity Lymphocytes provide specific defense (special kinds of leukocytes) –B cells and T cells The Innate and acquired defenses interact--- Helper T cells coordinate. Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms); usually a protein. Antibodies: circulating antigen-binding immunoglobulin, produced by B cells Antigen receptors: plasma membrane receptors on B and T cells

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24. APC- Antigen Presenting Cells Macrophages and B-Cells Display internalized antigens to Th cells.

25. Lymphocyctes Develop from Pluripotent stem cells in bone marrow or liver of fetus. Display specificity for a particular epitope (binding site) on an antigen. Recognize self from non-self cells 2 main types: –1. B Cells – 2. T Cells (thymus)

26. B-Cells --mature in bone marrow –Secrete antibodies (immunoglobulins) –Recognize intact antigens (on whole microbes found while patrolling body fluids—blood/lymph) –Humoral Response –Also have membrane antibodies on surface –APC-present antigens to Th, then they are activated and proliferate –-----------------------------------------------

27. T-Cells mature in thymus don’t secrete antibodies 2 types cytoxic (killer) -T Cells –Function in Cell-Mediated Immunity –Infected cells, cancerous, foreign cells –Receptors for Class I MHC –CD8 protein enhances binding to Th cell for activation.

28. Helper T-Cells Usually needed to activate B Cells & their proliferation –T-Dependent antigens Have receptors for class II MHC proteins CD4 protein enhances Th cell binding to B-cell in the humoral response. Function in both types of immune responses: 1. Humoral (free invaders in body fluids) 2. Cell-Mediated (infected, defective, foreign cell)

29. MHC Major histocompatability complex –Glycoproteins embedded in plasma membranes. –“self-markers”; Most polymorphic genes known –2 main classes: Class I MHC: located on all nucleated cells Class II MHC: specialized cells: macrophages & B cells. Function in antigen presentation-bind to antigen & facilitate antigen binding to a T cell.

30. Clonal selection- page 905 Antigens interact with specific lymphocytes, inducing immune responses and immunological memory Clonal selection: antigen-driven cloning of lymphocytes Antigen binds to receptor “Selected” cell proliferates. 2 “clones” of cells are produced. 1.Effector cells: short-lived cells that combat the antigen. 2. Memory cells: long-lived cells that bear receptors for the antigen. “Each antigen, by binding to specific receptors, selectively activates a tiny fraction of cells from the body’s diverse pool of lymphocytes; this relatively small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating the antigen.”

31. Induction of Immune Responses Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen.takes 10-17 days for max response. During this time, selected B- cells generate antibody producing effector cells (clonal selection) called Plasma cells: And Selected T-cells will produce effector T cells (no antibodies) Secondary immune response: immune response if the individual is exposed to the same antigen at some later time ~ Immunological memory Faster, more intense, longer than Primary

32. 2 Types of immune responses Humoral immunity B cell activation Production of antibodies Microbes circulating in blood and lymph (body fluids) Defend against free bacteria, toxins, and viruses in body fluids. Cell-mediated immunity Tc cell activation Binds to and/or lyses cells Defend against cells infected with bacteria, viruses, fungi, protozoa, and parasites; nonself cells, cancer.

33. Helper T cells—bring on the calvary Function in both humoral (antibody production) & cell-mediated immunity Activated by antigen presenting cells (APCs) bearing the class MHCII molecule CD4 (Th surface protein), enhances activation, as does Interlukin 1 (IL-1). Once activated, it proliferates, clone forms, Interlukin II (IL-2)further stimulates and helps activate B-cells and Tc Cytokines secreted (stimulate other lymphocytes): a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells b) interleukin-1 (IL-1): activates helper T cell to produce IL-2

34. Cell-mediated Immunity:cytotoxic T cells Destroy cells infected by intracellular pathogens and cancer cells Infected cell displays antigen (pieces of pathogen) on its…. Class I MHC molecules Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC) T C cell releases perforin, a protein that forms pores in the target cell membrane; cell lysis and pathogen exposure to circulating antibodies

35. Humoral response: B cells Stimulated by T-dependent antigens (help from TH cells) Macrophage (APCs) ingests pathogen; presents fragments on its Class II MHC protein to a … Helper T cell (CD4 protein enhances binding) Activated T cell secretes IL-2 (cytokines) that activate B cell… B cell differentiates into memory and plasma cells (antibodies)

36. Antibody Structure & Function Globular serum proteins Epitope: region on antigen surface recognized by antibodies 2 heavy chains and 2 light chains joined by disulfide bridges 2 Antigen-binding sites (variable region)

37. 5 classes of Immunoglobins IgM: 1st to circulate; First to respond to infection. indicates current infection; too large to cross placenta IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration IgD: do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells IgE: very large; small quantity; releases histamines-allergic reaction

38. Abnormal immune function Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin- dependent diabetes mellitus Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.

39. Antibody-mediated Antigen Disposal Neutralization (opsonization): antibody binds to and blocks antigen activity Agglutination: antigen (and microbe) clumping Precipitation: cross-linking of soluble antigens (proteins) Complement fixation: activation of 20 serum proteins, through cascading action, lyse viruses and pathogenic cells. –MAC attack

40. Immunity in Health & Disease Active: naturally acquired : conferred immunity by recovering from disease Active: artificially acquired: immunization and vaccination; produces a primary response & memory Passive immunity: transfer of immunity (antibodies) from one individual to another. Short term—weeks to months natural: mother to fetus via breast milk artificial: rabies antibodies ABO blood groups (antigen presence) Rh factor (blood cell antigen); Rh- mother vs. an Rh+ fetus (inherited from father). IgG

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