Immunity

1. Immunity

2. The lymphatic system • Plays an active role in defending the body from pathogens

3. Lymphatic System • Consists of branching network of lymph vessels, lymph nodes, thymus gland, tonsils, appendix, spleen, bone marrow • Lymphatic vesselscarry lymph fluid which is similar to interstitial fluid, contain valves to prevent backflow, and rely on muscles to help squeeze lymph along

4. The Lymphatic System • Three main homeostatic functions: • Lacteals receive (fats) lipoproteins and transport them to the bloodstream • Responsible for production, maintenance and distribution of lymphocytes • Helps defend body against disease

5. Lymphatic System • One-way system that begins with lymphatic capillaries • Take up fluid that has been diffused from, and not reabsorbed by, blood capillaries • Lymph flows one way • From a capillary to ever-larger lymphatic vessels • Finally to a lymphatic duct, which enters a subclavian vein (right and left), most lymph reenters the circulatory system at the left subclavian vein

6. Primary Lymphatic Organs • Thymus Gland • Contain T cells (lymphocytes) which mature here • Located along trachea behind the sternum in upper thoracic cavity • Produces thymic hormones (thymosin) • Red Bone Marrow • Contain stem cells • Area of maturation for B cells (lymphocytes) and most other types of white blood cells

7. Secondary Lymphatic Organs • Lymph Nodes - Capsule surrounding two distinct regions, cortex and medulla • Lymphocytes congregate in cortex when fighting off a pathogen • Macrophages concentrated in medulla - cleanse/filter lymph

8. Lymphoid Organs • Tonsils • Patches of lymphatic tissue located around the pharynx • First to encounter pathogens that enter via the nose and mouth • Spleen • Located in upper left region of abdominal cavity just beneath diaphragm • Lymphocytes cleanse blood of foreign particles

9. An animal must defend itself from the many dangerous pathogens it may encounter in the environment • Two major kinds of defense have evolved that counter these threats • Innate immunity and acquired immunity

10. Innate immunity • Is present before any exposure to pathogens and is effective from the time of birth

11. Acquired immunity, also called adaptive immunity • Develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances

12. INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response (antibodies) Mucous membranes Antimicrobial proteins Secretions Inflammatory response Invading microbes (pathogens) Cell-mediated response (cytotoxic lymphocytes) Natural killer cells Figure 43.2 • A summary of innate and acquired immunity

13. Nonspecific Defenses Against Infections • Bodies first line of defenses against infections are nonspecific, or do not distinguish between different types of invaders • A pathogen that successfully breaks through an animal’s external defenses • Soon encounters several innate cellular and chemical mechanisms that impede its attack on the body

14. External Defenses • Certain cells of the mucous membranes produce mucus a viscous fluid that traps microbes and other particles (protect respiratory and digestive systems)

15. In the trachea, ciliated epithelial cells • Sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs

16. Secretions of the skin and mucous membranes • Provide an environment that is often hostile to microbes • Secretions from the skin give the skin a pH between 3 and 5, which is acidic enough to prevent colonization of many microbes (sweat) • Stomach acid kills most bacteria swallowed with food

17. Internal Cellular and Chemical Defenses • Internal cellular defenses • Depend mainly on phagocytosis • Phagocytes, types of white blood cells • Ingest invading microorganisms

18. Phagocytic Cells • Phagocytes attach to their prey via surface receptors • And engulf them, forming a vacuole that fuses with a lysosome

19. Macrophages, a specific type of phagocyte can be found migrating through the body in the interstitial fluid and can be found in various organs of the lymphatic system • Macrophages and dendritic cells recognize pathogens and release cytokines which stimulate other white blood cells such as neutrophils and monocytes

20. Natural Killer Cells • Natural killer (NK) cells • Patrol the body and attack virus-infected body cells and cancer cells

21. Antimicrobial Proteins • Numerous proteins function in innate defense • By attacking microbes directly or by impeding their reproduction

22. Complement System • A collection of plasma proteins • Activated when pathogens enter the body • About 30 proteins make up the complement system (membrane attack complex) which can cause lysis of invading cells and help trigger inflammation

23. Interferon binds to receptors of non-infected cells • Causes them to prepare for possible attack • Produce substances that interfere with viral replication • Interferons are produced by virus-infected cells that help other cells to resist viruses, provide innate defense against viruses and help activate macrophages

24. Inflammatory Response • Histamine causes blood vessels to dilate and become leaky, increased blood flow and leakiness cause plasma to leak into interstitial fluid, tissues become red, swollen, hot • Chemicals attract white blood cells (phagocytes) to area, and they migrate out into tissues • White blood cells engulf bacteria, cell remains and dead white blood cells

25. Fever stimulates phagocytosis and inhibits growth of microorganisms, may be caused by toxins released by bacteria, or by chemicals released by white blood cells

26. Inflammatory Reaction • Neutrophils and monocytes migrate to the site of injury • Neutrophils and Monocytes mature into macrophages and phagocytize pathogens

27. Specific Immunity • In acquired immunity, lymphocytes provide specific defenses against infection • Acquired immunity is the body’s second major kind of defense, and involves the activity of lymphocytes • Exposure to antigen causes an increase in the number of cells (lymphocytes) that either attack invader directly or produce defensive proteins called antibodies

28. An antigen is any foreign molecule that is specifically recognized by lymphocytes and elicits an immune response from them • A lymphocyte actually recognizes and binds to just a small, accessible portion of the antigen called an epitope or antigenic determinant

29. Antigens usually have several antigenic determinants, so a single antigen can stimulate production of several different antibodies against it

30. Antigens can be molecules on the surface of viruses, bacteria, mold spores, cancer cells, pollen, household dust, or cell surfaces of transplanted organs and donated blood-are usually proteins or large polysaccharides on surface of virus or foreign cells, may also be toxins free in solution • Antigen comes from antibody-generating

31. Antigens that have been previously encountered are reacted to much more promptly and vigorously during the second or subsequent exposures • The body is able to recognize and destroy the foreign invader before it can produce disease, this is called immunity • Immunity is resistance to a specific invader

32. Immunity is usually acquired by natural infection, but can also be caused by vaccination • Vaccination (immunization) involves injecting a harmless variant of a disease-causing microbe (may be a killed bacteria or virus that has it’s DNA destroyed, or the molecules on their surface that are acting as antigens)

33. This causes our immune system to respond as if an actual infection has occurred • When we are actually exposed to the real pathogen (antigen), our immune system acts as if this is the second exposure and reacts more strongly (immunity)

34. Passive immunity, which provides immediate, short-term protection • Is conferred naturally when antibodies cross the placenta from mother to fetus or when antibodies pass from mother to infant in breast milk • Can be conferred artificially by injecting antibodies into a nonimmune person (travelers can be injected with antibodies to pathogens they are likely to encounter)

35. Antigen Recognition by Lymphocytes • The vertebrate body is populated by two main types of lymphocytes • The plasma membranes of both B cells and T cells have about 100,000 antigen receptor that all recognize the same specific antigen • B cells have antibodies (BCR=B-cell receptor) as antigen receptors, T cells have T cell receptors (TCR)

36. There are between 100 million and 100 billion different T cells and B cells each with their own specific antigen receptors • This allows our immune cells to recognize and bind to virtually any antigen we might ever encounter

37. Lymphocytes mount a dual defense • B cells or B lymphocytes mature in the bone marrow and produce antibodies, this results in humoral or antibody-mediated immunity (antibodies are dissolved in the blood or lymph-body fluids were formerly called “humors”) which defends primarily against bacteria and viruses in the body fluids

38. Newly formed lymphocytes are all alike • But they later develop into B cells or T cells, depending on where they continue their maturation

39. B Cell Receptors for Antigens • B cell receptors • Bind to specific, intact antigens • Are often called membrane antibodies or membrane immunoglobulins

40. Antibodies are proteins • Each chain has a constant region made of from the same sequence of amino acids, and a variable region that differs • The variable region forms the antigen-binding site-the part of the antibody that recognizes and binds to the antigen • Each antibody has two identical antigen binding sites, and can bind to two antigens simultaneously

41. Clonal Selection of Lymphocytes • In a primary immune response binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation, a process called clonal selection (expansion) • When antigen is first encountered, it activates a tiny number of lymphocytes, these selected cells divide to form a clone of cells (effector cells) that are specific for the stimulating antigen

42. Clonal selection of B cells • Generates a clone of short-lived activated effectorcells and a clone of long-lived memory cells

43. Primary immune response occurs when lymphocytes are exposed to an antigen for the first time • Lymphocytes previously unexposed to its particular antigen are called virgin cells • When first encountered, it takes several days for lymphocytes to become activated and antibodies to begin showing up in the blood

44. Virgin cells divide to become effector or plasma cells that produce antibodies, and memory cells • Memory cells last for decades, where they remain in lymph nodes ready to be activated by a second exposure to the antigen

45. In the secondary immune response • Memory cells facilitate a faster, more efficient response

46. Secondary immune response occurs during second exposure to same antigen • Elicits faster, stronger response and produces very high levels of more effective antibodies • Lasts much longer then primary response • Memory cell initiate secondary response by multiplying quickly to produce a much larger new clone of B cells

47. Antibody-Mediated Disposal of Antigens • The binding of antibodies to antigens • Is also the basis of several antigen disposal mechanisms • Main function of antibodies is to eliminate invading microbes or molecules by marking them for elimination

48. Effector mechanisms for antigen disposal • Neutralization-antibody binds to antigen to block harmful effects (may block viral binding sites or bind bacterial toxins making them ineffective) • Agglutination-two antigen biding sites on antibody cause agglutination or clumping of antigens • Precipitation-antibodies link dissolved antigen molecules together causing precipitation

49. Effector mechanisms of humoral immunity • Activation of complement proteins-activated complement proteins puncture plasma membrane causing cell to lyse or rupture

50. Immunoglobins • IgG - Main antibody type in circulation • IgM - Found in circulation Largest antibody • IgA - Found in secretions • IgD - Found on surface of immature B cells • IgE - Found as antigen receptors on basophils in blood and on mast cells in tissue