Test 3 Study Guide Innate Defenses 1. Describe the general characteristics of an innate defense.

-Nonspecific-present at birth -Offer immediate protection against a wide variety of pathogens and foreign substances -The protective mechanisms function the same way, regardless of the type of invader or injury 2. How does keratin contribute to defense? Keratin is resistant to bacterial enzymes and toxins 3. Describe how the following contribute to defense: a. Sebum- contains chemicals toxic to bacteria b. Stomach mucosa- is acidic (HCL) and has protein-digesting enzymes c. Mucus- traps microorganisms d. Saliva and tears- contains lysozyme e. Normal flora- produces antimicrobial substances f. Vaginal secretions- acidic secretions 4. What is the difference between free and fixed macrophages? Free macrophages can move to different areas: Ex- Neutrophils can squeeze inbetween endothelial cells via diapedesis. 5. Name three fixed macrophages. Kuppler cells of liver, Microglia of brain, and mast cells 6. Which phagocytes are mobilized by the inflammatory response? Neutrophils and macrophages 7. What is margination? How does it occur? -Endothelial cells develop adhesion molecules (CAMs) called selectins. -Neutrophils have CAMs called integrins. (The adhesion of white blood cells to the endothelial cells of blood vessels that occurs at the site of an injury during the early phases of inflammation.)

8. What is diapedesis? Neutrophils squeeze in between the endothelial cells to reach the injured site. 9. What is chemotaxis? Chemical signals that attract neutrophils and other white blood cells to the injured site. 10. Describe the process of phagocytosis. Cytoplasmic extension (amoeba-like) and membrane lined vacuole (vesicle) termed phagosome; fuses w/ lysosome to form phagolysosome. 11. What is adherence and how is it enhanced by opsonization? Adherence is recognition and binding to surface carbohydrates of the microorganism; opsonization makes the microbe more easily phagocytized. (Complement molecules, antibodies) 12. What is the respiratory burst? Liberation of free radicals (including nitric oxide) that can kill some more difficult to kill bacteria: tuberculosis -Oxidizing chemicals (hydrogen peroxide, H202, and a bleach) which result in potassium entry into phagolysosome that activate digestive enzymes 13. What are defensins? -Produced by a number of cells including neutrophils; antibioticlike chemicals that pierce the microorganisms. 14. What are natural killer cells? -Unique cells that can kill cancer cells and virus-infected cells before the adaptive response is activated -Type of large granular lymphocytes 15. How do natural killer cells detect pathogens? Detect a lack of self surface markers and/or presence of sugar surface markers on the target cell Use a dual receptor system in determining whether to kill or not to kill human cells. When cells are either under stress, are turning into tumors, or are infected, various stress-induced molecules are produced and are put on the surface of that cell.

The 1st NK cell receptor, called the killer-activating receptor, recognizes these stress-induced molecules. This interaction sends a positive signal which enables the NK cell to kill the cell to which it has bound unless the second receptor cancels that signal. 16. How are natural killer cells prevented from killing self cells? -This second receptor, called the killer-inhibitory receptor, recognizes MHC-I molecules that are also usually present on all nucleated human cells. -If MHC-I molecules are expressed on the cell, the killerinhibitory receptor sends a negative signal that overrides the kill signal and prevents the NK cell from killing that cell. 17. Under what conditions do formerly self cells fail to carry out #16? When viruses and malignant transformation sometimes interferes with the ability of the infected cell or tumor cell to express MHC-I molecules. 18. How does an NK cell kill another cell? Without the killer-inhibitory signal, the killer-activating signal is not overridden and the NK cell releases pore-forming proteins called peforins and granzymes. 19. What are perforins? Proteolytic enzymes that lyse the plasma membrane of the cell 20. What are granzymes? Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destructions of its structural cytoskeleton proteins and by chromosomal degradation. 21. Name four tissue responses to injury and infection in the inflammatory response. -Physical trauma -Intense heat -Irritating chemicals -Infection

22. What are the effects of the inflammatory response? -Prevents spread of microbes -Disposes of cell debris -Sets the stage for tissue repair 23. Where do the following physical features of inflammation come from? a. Redness- Vasodilation b. Warmth- Vasodilation c. Edema- Increased capillary permeability d. Pain- Pressure from exudate, lack of nutrition and bacterial toxins; prostaglandins and bradykinin e. Loss of function

24. What is exudate? Fluid containing clotting factors and antibodies 25. What purposes does edema serve in inflammation? -dilutes harmful substances brings in nutrients and oxygen -allows entry of clothing factors: gel-like fibrin mesh -the injured area is isolated and prevents spread of bacteria and other harmful substances to adjacent tissue 26. What are cytokines? Small protein hormones that stimulate or inhibit many normal cell functions. 27. What types of cells secrete cytokines (just give me the first 4)? Lymphocytes, antigen presenting cells, monocytes, & fibroblasts 28. Describe the action of cytokines (e.g., working distance and interaction with cell membrane). Act over short distances; they act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior (gene expression). 29. Describe the origin and function of the following cytokines: a. Interleukin-1- produced by monocytes and macrophages; promotes proliferation of helper T cells; acts on hypothalamus to cause fever.

b. Interleukin-2- secreted by helper T cells; costimulates the proliferation of helper T cells, cytotoxic T cells, and B cells; activates NK cells c. Interleukin-4- produced by activated helper T cells; costimulator for B cells; causes plasma cells to secrete IgE antibodies; promotes growth of T cells d. Interleukin-5- Produced by certain activated CD4+ T cells and activated by mast cells; costimulator for B cells; causes plasma cells to secrete IgA antibodies. 30. How do mast cells release histamine? Kinin Cascade 31. What are the effects of histamine? Vascular effects; dilation, increased permeability; exudation 32. What triggers the kinin cascade? Coagulation factor XII: Hageman factor 33. What does bradykinin do? -causes increased permeability of capillaries -causes arteriole vasodilation -chemotaxis of leukocytes -prompts neutrophils to release lysosomal enzymes -pain 34. How do prostaglandins contribute to the inflammatory response? Activation of the inflammatory response, production of pain, and fever. When tissues are damaged, white blood cells flood to the site to try to minimize tissue destruction. Prostaglandins are produced as a result. 35. How do prostaglandins contribute to clotting? PG12 is produced to have the opposite effect on the walls of the blood vessel where clots should not be forming. 36. What is complement? Group of 20 plasma proteins that circulate in blood in inactive state

37. What is the MAC and how does it kill bacteria (you do not have to know the specific proteins or the order in which they attach)? Membrane attack complex- Hole in target cell & influx of calcium kills cells 38. What are other functions of complement than forming an MAC? -Opsonization -Stimulation of mast calls and basophils to release histamine -Chemotaxis of neutrophil and other inflammatory cells 39. What do interferons do inside the cell when activated? -Infected cell releases interferons which are small proteins to protect adjacent uninfected cells -Stimulate the synthesis of a protein called PKR 40. What do pyrogens do? -fire starters secreted by leukocytes -in fever they are the chemical secreted by leukocytes and macrophages exposed by fibrogen substance, they reset the thermostat upwards 41. What happens to Zn and Fe during a fever and how does this contribute to defense? -they are stored in the spleen and liver and are unavailable to bacteria (which require these to multiply) 42. What do Toll-like receptors (TLRs) trigger the release of? -trigger immune response triggers the release of cytokines Test 3 Study Guide Adaptive Defenses 1. What are the two major types of adaptive immunity? Specific and Systemic

2. Describe humoral immunity in terms of: a. Mediation- Antibody-mediated b. Cells involved- B lymphocytes/plasma cells c. Targets- bacteria, bacterial toxins, free viruses in blood

3. Describe cellular immunity in terms of: a. Mediation- Cell mediated (direct cell killing or chemicals that enhance inflammation) b. Cells involved- T lymphocytes c. Targets- Virus-infected cells, parasite-infected cells, cancer cells, cells of foreign grafts 4. What are antigens? Substances that can evoke an immune response What are the two main characteristics of a complete antigen? Immunogenicity- ability to activate lymphocytes and antibodies Reactivity- ability to react with the activated lymphocytes and antibodies Name some molecules that can be a complete antigen. -Proteins (are the strongest antigens) -Nucleic acids -some lipids -many large polyschharides

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What is an incomplete antigen? -(haptens) the hapten combines with a body protein and can now evoke a full immune response 8. What is a hapten? Hapten- a small molecule that can elicit an immune response only when attached to a large carrier such as a protein What types of molecules are haptens? Small molecule- peptides, nucleotides, hormones 9. Which type of antigen is involved in allergies? Incomplete antigens

10. What are antigenic determinants? Are they single or multiple? -The specific portion of the molecule that evokes the immune response -most antigens have multiple different antigenic determinants

11. What is an epitope? Site of reaction by the immune response; triggers a specific immune response 12. How do plastics avoid evoking an immune response? Simple molecule with regularly repeating units 13. What type of chemical is an MHC protein? glycoproteins 14. What does MHC stand for? Major histocompatibility complex 15. Which type of cell does not have MHC I proteins? RBCs 16. How do MHC proteins respond to protein synthesis? MHC proteins take fragments of synthesized proteins to the cell surface -these fragments are what is recognized as self or foreign 17. What happens to MHC proteins when an intracellular pathogen has hijacked protein synthesis? MHC proteins will then take fragments of pathogen proteins to the surface: this prevents pathogens from hiding in cells 18. How do the following cells carry out their immune function? a. B lymphocytes- humoral (antibody mediated) b. T lymphocytes- cellular c. Antigen Presenting Cells (APCs)- macrophages, dendritic cells, some B lymphocytes 19. Where do all lymphocytes originate? -In the red bone marrow 20. Where do T cells become immunocompetent? In the thymus gland

21. What must T cells do and not do to become immunocompetent? -Can detect self and do not attack -Can detect non-self and do attack 22. What is self-recognition and why is it positively selected? T cells must be able to recognize your own MHC proteins 23. What is self-tolerance and why is it negatively selected? T cells that with T cell receptors that recognize self-antigens are weeded out 24. Where do B lymphocytes mature? In the red bone marrow where they form 25. What is anergy? Inability of an immune cell to mount a complete response against its target 26. What is clonal deletion? Deletion of lines that react to self or do not recognize self 27. What is the difference between primary and secondary lymphoid organs? Primary: Thymus & red bone marrow Secondary: All other lymphoid tissue 28. At what point do B and T lymphocytes become immunocompetent? When they can recognize foreign antigens 29. How is diversity of antibodies generated? Genetically determined- diversity of antibodies is generated by shuffling a few hundred genes to create millions of permutations 30. Where do lymphocytes colonize lymphoid tissue? Spleen, Lymph nodes, & lymphoid follicles 31. What is the very last stage of maturation in lymphocytes (look at (3) on slide 20)? Mature (antigen-activated) immunocompetent lymphocytes circulate continuously in the bloodstream and lymph and throughout the lymphoid organs of the body

32. What do APCs do? Engulf antigens and present fragments of the antigen on their own cell surface 33. What types of cells can be APCs? Macrophages, dendritic cells in connective tissue, Langerhans cells in skin, activated B lymphocytes 34. Describe the steps of antigen presentation (slide 24). 1. phagocytosis or endocytosis of antigen 2. digestion and turn into peptide fragments 3. vesicles containing peptide fragments and MHC-II molecules fuse 4. peptide fragments bing to MHC-II molecules 5. vesicles undergoes exocytosis and antigen MHC-II complexes are inserted into plasma membrane 35. What is the difference between MHC-I and MHC-II proteins? The Class I MHC molecules process endogenous (intracellular) peptides/antigens whereas the Class II process exogenous (extracellular) peptides/antigens. 36. How does a nave B lymphocyte become activated? When it binds to a foreign antigen 37. What is clonal selection? This is a specific B cell now begins to divide to make many other B cells exactly like it 38. What are memory B cells? These cells will be triggered if some person encounters the same antigen again 39. Distinguish between the primary immune response and the secondary immune response. -Primary immune response: first exposure to antigen, takes 3-6 days to develop, the antibodies produced by the plasma cells peak at 10 days, then decline, most associated with IgM -Secondary immune response: occurs if re-exposed to same antigen,

faster 2-3 days, higher concentration of antibodies, more prolonged weeks to months, more effective (potent), most associated with IgG 40. Which immunoglobulin is most associated with the primary immune response? IgM 41. Which immunoglobulin is most associated with the secondary immune response? IgG 42. What is the difference between naturally and artificially acquired active immunity? Naturally acquired- you get the illness Artificially acquired- vaccines 43. How do vaccines work? Only a portion of the antigen given, most are dead or attenuated (thus minimizing symptoms of disease), cause a primary immune response and development of memory cells 44. What is passive humoral immunity? Antibodies (immunoglobins) come from another person or animal, not made by your own plasma cells, maternal transger to fetus: IgG, gamma globulins in serum 45. How does passive humoral immunity affect immunity memory? Memory does NOT occur 46. What is the basic structure of antibodies? 4 polypeptide chains: 2 identical heavy chains (H), 2 identical light chains (L) 47. What is the constant region? Same within an immunoglobulin classes 48. What is the variable region? Vary among immunoglobulin classes

49. What is the difference between the Fab region and the Fc region? Fab region- 2 on each antibody, site for binding antigen Fc region- site where antibodies bind to other cells of the immune system

50. Which immunoglobulin is the most abundant, is involved in the secondary immune response, and is the only one to cross the placental barrier? IgG 51. Which immunoglobulin is found in many secretions and is decreased during stress? IgA 52. Which immunoglobulin is first to be secreted by plasma cells in the primary immune response? IgM 53. Which immunoglobulin is involved in activation of B cells? IgD 54. Which immunoglobulin is involved in allergic reactions? IgE 55. What is somatic recombination? Shuffling and recombination of gene segments 56. How is antibody diversity achieved?

57. Name four ways in which antibody binding contributes to the immune response (slide 47).

58. How do APCs contribute to the function of T lymphocytes? Activation 59. What is the trigger for T cell action? Binding to a specific antigen (same as in B cells)

60. What does T cell recognition require? The antigen (non-self) and Self (a MHC protein) 61. What are TAPs? Transporter associated with antigen processing within a cell 62. Which type of T cell responds to MHC-I proteins (slide 66)?

63. What protein is used by cytotoxic T cells to bind foreign MHC-I proteins? 64. Which type of T cell uses MHC-II proteins (slide 67)?

65. What protein is used by helper T cells to bind to MHC-II proteins?

66. How does a helper T cell respond to CD4 binding with a foreign antigen (slide 68)? 67. What do TH2 cells do? 68. What do TH1 cells do? 69. What are the targets of cytotoxic T cells? 70. How do cytotoxic T cells kill their targets? 71. What is the function of suppressor T cells? 72. Describe the function and type of antigen response of (slide 80) a. Helper T-cell b. Cytotoxic T-cell c. Memory T-cell d. Suppressor T-cell e. Plasma cell f. Memory B-cell g. NK cell