1. Chapter 17 Genetics of Immunity Genetics Spring 2016

2. I. The Importance of Cell Surfaces A. Viruses 1. Nonliving a. single or double stranded DNA or RNA wrapped in protein b. needs host cell to replicate

3. 2. Human chromosomes have viral DNA sequences a. virus inserts its DNA into host genome b. host cell will replicate viral DNA along with its own c. viral DNA also gets translated into viral protein

4. 3. Viral DNA cannot be repaired a. complex viruses have high mutation rates b. creates many strains of the same virus c. vaccine development is difficult

5. B. Genetic control of immunity 1. Affects are usually polygenic a. susceptibility or resistance to diseases b. risk of developing autoimmune or allergic conditions

6. 2. Powerful single genes a. encode antibodies or cytokines i. proteins that attack foreign antigens b. encode antigens i. molecule on the surface of a cell ii. Elicits an immune response iii. Also used to mark body’s cells as “self”

7. C. Blood groups 1. ABO Blood Groups a. Combinations of two antigens- antigen A and antigen B- create 4 blood types b. Combinations of two antibodies- Anti-A and Anti-B- are associated with each c. Antibodies will attack specific antigens and cause blood cells to clump

8. Blood TypeAntigenAntibody Type AAAnti-B Type BBAnti-A Type ABA and BNeither Type ONeitherAnti-A and Anti-B

10. 2. The Rh Factor a. ABO blood types are further differentiated i. either positive (+) or negative (-) b. this is determined by the Rh antigens i. there are actually 3 Rh antigens ii. A person who has any of the Rh antigens is Rh+ iii. A person who has NO Rh antigens is Rh-

11. c. Anti-Rh antibodies are only created upon stimulation i. ex. An Rh- woman who has Rh+ children ii. First pregnancy is ok iii. After birth, mother’s body makes Anti-Rh antibodies iv. Second pregnancy, antibodies will attack fetal blood cells

13. D. The human leukocyte antigens 1. The Major Histocompatibility Complex (MHC) a. refers to a 6 million-base-long cluster of genes i. located on the short arm of chromosome 6 b. includes about 70 genes ii. Classified into 3 functional groups

14. 2. Class I and II MHC encode Human Leukocyte Antigens (HLA) a. HLAs are located on every cell, except Red Blood Cells b. Some HLAs are used to alert the immune system of invaders i. cells with these are called antigen-presenting cells

16. II. The Human Immune System A. Physical barriers 1. Structures and fluids that keep pathogens from entering the body a. Skin b. Mucous membranes 2. Barriers are nonspecific- keep out anything foreign

18. B. The Innate Immune Response 1. Provides a rapid, broad defense 2. Inflammation creates a hostile environment a. Phagocytes are sent in b. Plasma accumulates i. dilutes toxins and ii. brings in antimicrobial chemicals c. increased blood flow warms area

20. 3. Three major classes of proteins participate in innate response a. The Complement System i. plasma proteins that assist in several other defense mechanisms ii. Puncture bacterial plasma membranes iii. Dismantle viruses iv. Trigger the release of histamine

21. b. Collectins i. detect slight differences in cell surfaces ii. Used to decipher bacteria and yeast from human cells iii. Can even detect some viruses c. Cytokines i. alert the immune system to cells infected with viruses ii. Cause fever to stop the growth of microbes

22. C. The Adaptive Immune Response 1. Carried out by B cells and T cells a. B cells produce antibodies i. called the Humoral immune response b. T cells produce cytokines and activate other cells i. called the Cellular immune response

23. 2. The Humoral Immune Response a. Antibody response begins with antigen-presenting cell i. Activates T cell ii. In turn activates B cell that corresponds with foreign antigen

24. b. T cells release cytokines i. stimulates B cell to divide c. B cell produces two types of cells i. plasma cells that secrete antibodies ii. Memory cells respond to foreign antigens faster

25. d. Construction of Antibodies i. made of several polypeptides ii. Simplest antibodies are Y shaped iii. Able to bind certain antigens at the tips of the Y e. Functions of antibodies i. binding may inactivate a pathogen ii. Can clump pathogens to make them more visible

26. 3. The Cellular Immune Response a. T cells i. descend from stem cells in bone marrow ii. Travel to the Thymus to mature and differentiate b. Types and functions of T cells i. Helper T cells stimulate B cells to produce antibodies ii. Killer T cells contain toxic chemicals to kill infected body cells

27. III. Abnormal Immunity A. Inherited immune deficiencies 1. More than 20 types a. affect both innate and adaptive immunity

28. 2. Chronic Granulomatous Disease a. some phagocytes are unable to kill bacteria i. lack the enzyme called oxidase b. 4 genes encode this enzyme i. so there are 4 ways to inherit the disease ii. All are X linked

29. 3. Severe combined immune deficiencies (SCID) a. affect both humoral and cellular immunity i. i.e. ALL adaptive immunity b. about half of SCID cases are X-linked i. severe cases cause death by 18 months of age c. lack of B and T cells means the person cannot fight infection

31. B. Acquired immune deficiency syndrome (AIDS) 1. Acquired by infection with HIV a. a virus that gradually shuts down the immune system

32. 2. Progression of HIV a. begins by entering macrophages i. virus binds surface receptors ii. Contorts cell in a way that allows virus to enter iii. Once inside, virus inserts DNA into a chromosome to be transcribed and translated iv. New viral parts are assembled and burst from the cell

33. b. Same process occurs with Helper T Cells i. loss of helper T cells inhibits B cells ii. B cells never receive signals to make antibodies iii. Bacterial infections become a serious problem c. later during infection, Killer T Cells are killed i. body becomes more vulnerable to viral infections and cancer

34. 3. Treatments for AIDS a. AIDS has become treatable i. still a chronic, lifelong illness ii. no longer a death sentence b. 3 types of drugs have cut death rates dramatically i. reverse transcriptase inhibitors ii. Protease inhibitors iii. Entry inhibitors

35. C. Autoimmunity 1. The immune system attacks the body a. antibodies that attack the body are called “autoantibodies” b. symptoms reflect the cell types under attack i. ex. Ulcerative colitis affects colon cells ii. Causes severe abdominal pain

36. 2. Symptoms of autoimmune conditions can arise by other mechanisms a. makes diagnosis difficult b. ex. Hemolytic anemia may be: i. autoimmune ii. Inherited iii. A reaction to toxin exposure

37. 3. Autoimmune disorders are more common among women a. Ex. Scleroderma i. means “hard skin”

38. b. Symptoms i. fatigue ii. Swollen joints iii. Stiff fingers iv. A masklike face c. may actually be caused by lingering fetal cells

39. D. Allergies 1. An allergy is an immune response a. responds to an “allergen” i. substance that doesn’t actually present a threat b. allergens are usually carried in the air i. enter the respiratory tract

40. c. size of allergen may determine type of allergy i. grass pollen is large & causes hay fever ii. Dust mites are small & trigger asthma

41. 2. Both humoral & cellular immunity produce allergic responses a. Humoral i. specific antibodies (IgE) trigger release of histamine and heparin ii. Causes inflammation b. Cellular i. allergens activate Helper T cells to release specific cytokines ii. These cytokines control IgE antibody production

42. 3. Allergies have become very common over the last century a. suggests an environmental influence over genetics b. could also be a holdover of immune function that was important in the past

43. IV. Altering Immune Function A. Vaccines 1. Inactive or partial form of a pathogen a. stimulates immune system i. B cells make antibodies ii. Secondary response occurs when person encounters pathogen

44. 2. Some vaccines contain whole virus or bacteria a. slight chance of illness b. pathogen may mutate

45. 3. Methods of delivery a. injections i. most common b. nasal sprays c. modified fruits & veggies i. makes sense in theory ii. Difficult in practice

46. B. Immunotherapy 1. Monoclonal antibodies a. mass production of a single B cell i. causes mass production of a single antibody b. targets a specific disease ii. Such as cancer c. boosts humoral immunity

47. 2. Cytokines a. used to treat a variety of conditions i. interferon (IF) treats cancer, genital warts & multiple sclerosis ii. Interleukin-2 (IL-2) treats kidney cancer reoccurrence b. drug development is difficult i. cytokines only remain active for a short period of time ii. Must be delivered precisely when needed

48. C. Transplants 1. Types a. Autograft i. transfers tissue from one part of a person’s body to another b. Isograft i. tissues from a monozygotic (identical) twin

49. c. allograft i. tissues from the same species but not genetically identical d. xenograft i. transplants tissues from one species to another

50. 2. Rejection reactions – or acceptance a. Immune system recognizes foreign tissues i. more differences in cell surfaces causes faster rejection b. methods to dampen rejection i. matching HLA types ii. Stripping donor tissue of antigens iii. Immunosuppressive drugs inhibit antibodies & killer T cells