THE IMMUNE SYSTEM

1. THE IMMUNE SYSTEM

2. The Immune System

3. 1st Line of Defense: Surface Barriers • The Skin: heavily keratinized epithelial membrane presents a physical barrier to most microorganisms that swarm on the skin; keratin is resistant to most weak acids and bases and to bacterial enzymes and toxins

4. 1st Line of Defense (cont’d) • Mucous Membranes: serve as physical barriers and produce a variety of protective chemicals • acidity of skin secretions (pH of 3-5) inhibits bacterial growth and sebum contains chemicals that are toxic to bacteria • the stomach mucosa secretes a [ ]’d HCl solution and protein-digesting enzymes to kill microorganisms

5. 1st Line of Defense (cont’d) • Mucous Membranes: • saliva and lacrimal fluid (external eye) contain lysozyme, an enzyme that destroys bacteria • sticky mucous traps many microorganisms that enter the digestive and respiratory passageways • the respiratory tract mucosae also have structural modifications such as vibrissae and cilia

6. 2nd Line of Defense: Internal Defenses • Phagocytes • the chief phagocytes are macrophages which derive from circulating WBCs called monocytes search for cellular debris or foreign invaders; are called free (move about regions) or fixed (permanent to one organ) • neutrophils are the most abundant type of WBC and become phagocytic on encountering infectious material in the tissues; also contain the chemical, defensins, to kill

7. 2nd Line of Defense: Internal Defenses • Phagocytes (cont’d) • eosinophils are another type of WBC and are weakly phagocytic but very important in defending the body against parasitic worms • mast cells, more associated with their role in allergies, have been shown to have an ability to bind with and ingest a wide range of bacteria, and then to kill the internalized bacteria

8. 2nd Line of Defense: Natural Killer Cells • Police the body in the blood and lymph • Can lyse and kill cancer cells and virus-infected body cells before the immune system is activated and enlisted in the fight • Part of large granular lymphocytes • Not phagocytic; attack the target cell’s membrane and release cytolytic chemicals called perforins which causes the nucleus to disintegrate

9. 2nd Line of Defense: Inflammation • Inflammation: tissue response to injury such as a physical trauma, intense heat, and irritating chemicals, as well as to infection by viruses, fungi, and bacteria • (1) prevents the spread of damaging agents to nearby tissues (2) Disposes of cell debris (3) Sets the stage for repair processes

10. 2nd Line of Defense: Inflammation (cont’d) • 5 Cardinal Signs of Acute Inflammation: • (1) Redness (2) Heat (3) Swelling (4) Pain (5) Loss of function • The inflammatory process begins with a flood of inflammatory chemicals into the ECF • Injured tissue cells, phagocytes, lymphocytes, mast cells, and blood proteins are sources of these chemicals (see following slide)

11. Inflammatory Chemicals • Include histamine, kinins, prostaglandins, complement, and cytokines • Cause small blood vessels in the vicinity to dilate and leads to hyperemia; redness and heat • Chemicals also increase the permeability of local capillaries and allows exudate (fluid containing proteins such as clotting factors and antibodies) to seep from the bloodstream into the tissue spaces; swelling and pain (presses on nerve endings)

12. Inflammation (cont’d) • Edema: (1) helps to dilute harmful substances that may be present (2) brings in large quantities of oxygen and nutrients needed for repair (3) allows the entry of clotting proteins • If an epithelial barrier has been breached, -defensins (antibiotic-like chemicals) increases to help control bacterial and fungal colonization

13. Inflammation (cont’d): Phagocyte Mobilization • Leukocytosis: chemicals released by injured cells promote rapid release of neutrophils from red bone marrow • Margination: the neutrophils cling to the inner walls of the capillaries; also known as pavementing • Diapedesis: chemical signaling causes the neutrophils to squeeze through the capillary walls

14. Inflammation (cont’d): Phagocyte Mobilization • Chemotaxis: neutrophils and other WBCs are attracted to the site of injury by chemotactic agents and phagocytosis

15. 2nd Line of Defense: Antimicrobial Proteins • Interferon: a virus-infected cell will help protect cells that have not yet been infected by secreting small proteins called interferons (IFNs); they interfere with viral replication in those cells by blocking protein synthesis at the ribosomes; also has an anti-cancer role by activating macrophages and natural killer cells

16. Inflammation (cont’d): Antimicrobial Proteins • Complement: a group of at least 20 plasma proteins that, when activated, amplify virtually all aspects of the inflammatory process, kill bacteria and other cell types by cell lysis

17. 2nd Line of Defense: Fever • The body’s thermostat (in hypothalamus) is normally set at 36.2 °C (98.2 °F) but resets upward in response to chemicals called pyrogens (pyro=fire), secreted by leukocytes and macrophages exposed to bacteria; moderate fever causes the liver and spleen to sequester iron and zinc, which bacteria need to multiply

18. 3rd Line of Defense: Adaptive (Specific) Defenses • Antigens: substances that can mobilize the immune system and provoke an immune response; most are large, complex molecules (both natural and manmade) that are not normally present in the body; eg. bacteria, viruses, mismatched RBCs • Complete Antigens: foreign proteins, nucleic acids, some lipids, and many large polysaccharides; proteins are the strongest antigens

19. Antigens (cont’d) • Incomplete Antigens: Haptens; small molecules that link up with the body’s own proteins; haptens are reactive but not immunogenic unless attached to protein carriers; include penicillin, poison ivy, animal dander, some detergents, cosmetics • haptens can produce harmful reactions, called allergies

20. 3rd Line of Defense: Adaptive (Specific) Defenses (cont’d) • Antibodies: also called immunoglobulins; soluble proteins secreted in response to an antigen, and they are capable of binding specifically with that antigen; they constitute the gamma globulin part of blood proteins

21. 3rd Line of Defense: Adaptive (Specific) Defenses (cont’d) • Immunocompetent Lymphocytes: arise in red bone marrow and mature into T cells (T lymphocytes) or B cells (B lymphocytes) • T Cells: manage the immune response and some directly attack and destroy foreign cells; oversee cell-mediated immunity • B Cells: produce plasma cells, daughter cells that secrete antibodies into the blood or other body fluids; oversee humoral immunity

22. 3rd Line of Defense: B Cells • Humoral immune response (anti-body mediated) occurs when antigens bind to the B cells • Clonal selection occurs to stimulate the B cell to grow and then to multiply rapidly • Most of the clone become plasma cells, which are antibody-secreting effector cells • B cells secrete limited amounts of antibodies, but plasma cells secrete 2000 molecules per second for 4 to 5 days

23. 3rd Line of Defense: B Cells • The clone cells that do not become plasma cells become long-lived memory cells which will mount an immediate humoral response if they encounter the same antigen again • Primary immune response occurs 3-6 days after the antigen challenge; secondary immune responses are faster, more prolonged, and more effective because the memory cells are already on alert

24. 3rd Line of Defense: B Cells • Active Humoral Immunity: (1) naturally acquired during bacterial and viral infections (2) artificially acquired when we receive vaccines (contain dead or weakened pathogens); tetanus • Passive Humoral Immunity: antibodies obtained from a human or animal donor egs. breast milk, serum to treat snake bites, botulism, rabies (these would kill before active immunity could be established)

25. 3rd Line of Defense: T Cells • 2 major populations of effector T cells • T4 Cells: display cell differentiation glycoprotein 4 (CD4); primarily helper T cells • T8 Cells: display cell differentiation glycoprotein 8 (CD8); cytotoxic cells • destroy any cells in the body that harbour anything foreign • the B cells prepare the antigen for disposal by the T cells

26. 3rd Line of Defense: T Cells • T Cell Activation: (1) Antigen Binding: T cell antigen receptors bind to an antigen-MHC protein (self body cell) complex on the surface of a body cell; not all T cells can bind to all antigen-MHC protein complexes (2) Costimulation: before a T cell can proliferate and form a clone, it must recognize on or more costimulatory signals; physical or chemical signals that nudge the T cells either to complete their activation process or to abort activation entirely

27. 3rd Line of Defense: T Cells • T Cell Activation: (3) Cloning: once activated the T cells proliferate to form a clone of cells that differentiate and perform functions according to their T cell class; occurs within a week after a single exposure; death of T cells occurs between days 7 and 30; clone members become memory T cells for secondary responses

28. Summary • T8 cells prevent infectious microorganisms, hidden within cells from antibody surveillance, from killing their cellular hosts • Helper T4 cells costimulate both other T cells and B cells and recruit nonspecific defenses; without them there is no adaptive immune response because they direct or help complete the activation of all other immune cells (AIDS) • Suppressor T cells prevent undesirable immune reactions

29. “and the Band Played On”Movie – To be shown in PMD lab