1. GEORGE B. JOHNSON Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display PowerPoint ® Lectures prepared by Johnny El-Rady 22 How the Animal Body Defends Itself Essentials of The Living World First Edition

2. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.1 Skin: The First Line of Defense The vertebrate is defended from infection the same way knights defended medieval cities 1. Walls and moats Skin and mucous membranes provide a first barrier 2. Roaming patrols Cellular counterattack should first barrier be breached 3. Sentries Specific immune response scans for foreign cells or viruses

3. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Our largest organ (about 15% of our total weight) Provides the first line of defense against microbes Has two distinct layers Outer epidermis Inner dermis A subcutaneous layer lies underneath the dermis Skin

4. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.2 A section of human skin

5. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Epidermis 10-30 cells thick Stratum corneum – Outermost layer Cells continuously being replaced by others from below Basal layer – Innermost layer Dermis 15-40 times thicker than the epidermis Provides structural support for the epidermis Subcutaneous layer Fat-rich cells that act as shock absorbers and insulators

6. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Digestive tract Lysozyme in saliva breaks down bacterial cell walls Acidic environment of the stomach kills microbes Respiratory tract Cells of the small bronchi and bronchioles secrete mucus Traps microorganisms They also possess cilia Sweep the mucus towards the glottis Other External Surfaces

7. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.2 Cellular Counterattack: The Second Line of Defense Lymphatic system Central location for storage and distribution of immune cells and proteins A network of capillaries, ducts, nodes and organs Fig. 22.3

8. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Three types of white blood cells Macrophages Neutrophils Natural Killer Cells All three can distinguish between body cells (self) and foreign cells (nonself) Failure to make this distinction correctly results in autoimmune diseases Cells That Kill Invading Microbes

9. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Macrophages Ingest bacteria Most patrol the byways of the body as precursor cells called monocytes Fig. 22.4 Neutrophils Release chemicals killing bacteria and themselves in the process Natural killer cells Attack virus-infected body cells and cancer cells Puncture membranes Fig. 22.5

10. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Complement system ~ 20 different proteins Circulate freely in blood plasma in inactive form Aggregate to form a membrane attack complex Form holes in the invading microbe Proteins That Kill Invading Microbes Can augment the effects of other body defenses Fig. 22.7

11. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Interferons Three major categories Alpha Beta Gamma Proteins That Kill Invading Microbes Prevent viral replication and protein assembly Defends against infection and cancer

12. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Can be broken down into three stages 1. Infected or injured cell releases chemicals Histamine and prostaglandins 2. Chemicals cause blood vessel to expand and become more permeable Redness and swelling 3. Phagocytes migrate to the site of infection or injury Neutrophils, then monocytes/macrophages The Inflammatory Response

13. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.8 The events in a local inflammation

14. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display When macrophages counterattack, they send a message to the brain to raise body’s temperature Fever inhibits microbial growth However, very high fevers are dangerous because they can inactivate cellular enzymes Fevers greater than 40.6 o C (105 o C) are often fatal The Temperature Response

15. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.3 Specific Immunity: The Third Line of Defense Specific immunity involves the actions of white blood cells (WBC) WBC are very numerous Two out of every 100 body cells WBC come in different types Lymphocytes T cells and B cells

16. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Originate in bone marrow and migrate to Thymus Develop ability to identify foreign agents by antigens present on their surface An antigen is a molecule that provokes a specific immune response Four main types of T cells Helper (T H ) – Initiate the immune response Cytotoxic (T C ) – Lyse virus-infected cells Memory – Provide a quick response on re-exposure Suppressor – Terminate the immune response T cells

17. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Originate and mature in the bone marrow The B refers to a region of chicken called Bursa, where they were first characterized Circulate in blood and lymph Proliferate upon antigen exposure into Plasma cells Produce antibodies Memory cells Provide a quick response on re-exposure B cells

18. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.4 Initiating the Immune Response Every cell in the body carries surface markers called major histocompatibility (MHC) proteins MHC proteins are different for each individual So they act as “self” markers Antigen-presenting cells Ingest foreign particles and partially digest them Process antigens and move them to surface of cell membrane There they are complexed with MHC proteins T cell receptors can only interact with cells that have this combination of MHC and antigen

19. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.9 How antigens are presented Lymphocyte Antigen- presenting cell

20. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.4 Initiating the Immune Response Macrophages inspect the surface of cells looking for “self” MHC proteins If a cell displays “nonself” MHC protein-antigen combinations The macrophage will secrete an alarm signal, the protein interleukin-1 Stimulates helper T-cells to initiate Cellular immune response by T cells Humoral immune response by B cells

21. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.5 T-cells: The Cellular Response Helper T cells get activated upon binding “nonself” MHC protein-antigen complex of the macrophage Helper T cells secrete interleukin-2 Stimulates proliferation of cytotoxic T cells Recognize and destroy cells with the specific antigen found on the antigen-presenting cell Cytotoxic T cells will also attack transplanted tissue and cause graft rejection The drug cyclosporin inactivates cytotoxic T cells

22. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.10 The T cell immune defense

23. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.6 B-cells: The Humoral Response B cells recognize invading microbes, but do not go on the attack themselves Rather, they mark the pathogen for destruction by non- specific immune defenses B cells can bind to free and unprocessed antigens Antigens are endocytosed, processed and presented on the surface with an MHC protein Helper T cells recognize this complex and stimulate B cells to proliferate into Memory cells Plasma cells, which produce antibodies

24. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.11 The B cell immune defense

25. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Antibodies: Proteins in class immunoglobulins (Ig) Five different subclasses IgM First to be secreted during the primary response IgG Major one secreted during the secondary response IgD Receptor for antigen on surface of B cells IgA Form in external secretions (saliva and milk) IgE Promotes release of histamine

26. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Plasma cells Produce large amounts of the same antibody that initiated the immune response Antibodies bind to the antigens and flag the cells for destruction by complement, macrophages or NK cells Fig. 22.12 Memory B cells Circulate blood and lymph, waiting for future exposure Second response is amplified about a millionfold

27. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display B cells can make an estimated 10 6 to 10 9 different antibody molecules Immune receptor genes are assembled by a process called somatic rearrangement DNA segments that code for different parts of the receptor molecule are stitched together Further antibody diversity is generated by Imprecise DNA rearrangements Random mutations Antibody Diversity

28. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.13 The lymphocyte receptor molecule is produced by a composite gene Constant region Joining region Diversity region Variable region

29. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.15 22.7 Active Immunity Through Clonal Selection The first encounter with a foreign antigen is termed the primary immune response Only a few B cells or T cells can recognize the antigen Binding of antigen to its receptor on lymphocyte stimulates cell division A clone is produced This process is called Clonal selection

30. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The second encounter with a foreign antigen is termed the secondary immune response This time, there is a large clone of lymphocytes that can recognize the antigen The immune response is now swifter and stronger Fig. 22.15

31. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.16 How the immune response works

32. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.8 Evolution of the Immune System Even bacteria can defend themselves from viruses Use restriction endonucleases that cut foreign DNA lacking a specific pattern of methylation Mutlicellular organisms have to defend against cellular invaders as well!

33. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Mark cell surfaces with protein self labels Employ a negative test Special amoeboid cells engulf any invading cell that lacks these labels Invertebrates In 1882, Elie Metchnikoff discovered that invertebrates have immune defenses He pierced sea star larva with a rose thorn Next day tiny phagocytic cells covered the thorn Fig. 22.17

34. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The invertebrate immune response shares several features with that of vertebrates 1. Phagocytes 2. Distinguishing self from nonself 3. Complement 4. Lymphocytes 5. Antibodies Invertebrates

35. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The modern vertebrate immune system first appeared in jawed fishes Sharks are the oldest surviving group Have an immune response similar to that seen in mammals Most notable difference: Antibody-encoding genes are arrayed somewhat differently Vertebrates

36. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.18 How immune systems evolved in vertebrates

37. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.9 Vaccination The year 1796 marked the birth of immunology Edward Jenner observed that milkmaids who got cowpox rarely got smallpox He inoculated patients with cowpox and thus protected them from smallpox Fig. 22.19

38. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Vaccination is the introduction into the body of a dead or disabled pathogen harmless microbe with pathogen proteins displayed on its surface Vaccination triggers an immune response without causing an infection Circulating memory B cells are produced Elicit a quicker and larger immune response in an actual infection Vaccination may not provide effective defense in the future, if pathogen’s surface proteins are altered Example: Influenza virus

39. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.21 Researchers are attempting to construct an AIDS vaccine

40. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.10 Antibodies in Medical Diagnosis Blood typing ABO system is the major group of RBC antigens The immune system is tolerant to its own antigens People who are Type A, make antibodies against the B antigen People who are Type B, make antibodies against the A antigen People who are Type AB, do not make either anti-A or anti-B antibodies People who are Type O, make both anti-A and anti-B antibodies

41. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.22 Blood typing Clumping of RBCs

42. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display A group of antigens found on RBC Rh-positive people have them; Rh-negative people don’t Of particular significance when Rh-negative mothers give birth to Rh-positive babies Mother may be exposed to fetal blood and thus produce anti-Rh antibodies A subsequent Rh-positive pregnancy leads to erythroblastosis fetalis Can be prevented by injecting the mother with anti-Rh antibodies Rh factor Monoclonal antibodies Antibodies specific to one antigen Used in pregnancy tests to detect the hCG hormone

43. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.11 Overactive Immune System Autoimmune Diseases Cytotoxic T cells and B cells lose their ability to distinguish “self” cells from “nonself” cells Body attacks its own tissues Examples: Mutliple sclerosis Type I diabetes Rheumatoid arthritis Lupus Graves’ disease

44. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.23 22.11 Overactive Immune System Allergies Body mounts a major defense against a harmless substance Hay fever House dust mite Mast cells initiate the inflammatory response Release histamine Capillaries swell Mucus production increases

45. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.24 An allergic reaction In asthma, histamine causes the narrowing of air passages in the lungs

46. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22.12 AIDS: Immune System Collapse AIDS (acquired immunodeficiency syndrome) was first recognized as a disease in 1981 Worldwide, 42 million have become infected 24 million have died In the US, the total through the end of 2002 is about 887,000 cases and 502,000 deaths

47. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Fig. 22.25 The AIDS epidemic in the United States

48. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display AIDS is caused by HIV (human immunodeficiency virus) HIV attacks and cripples the immune system by inactivating cells that have CD4 receptors Found in macrophages and helper T cells This leaves the immune system unable to mount a response to any foreign antigen A variety of otherwise commonplace infections prove fatal Death by cancer becomes far more likely