Complement ASSIGNED READING CHAPTER 14: p 335-356 OUTLINE/SUMMARY

1. Complement Components
2. Complement Activation
   • Classical pathway
   • Alternative pathway
   • Membrane attack complex
3. Regulation of Complement
4. Biological Consequences
   • Cell lysis
   • Inflammation
   • Opsonization
   • Viral neutralization
   • Solubilization of immune complexes
5. Complement Deficiences

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS:

ON COMPLETION OF THIS SECTION THE STUDENT SHOULD BE ABLE TO:

1. Describe the nomemclature of complement components
2. Draw a concept map of the classical complement cascade
3. Draw a concept map of the alternate pathway of complement activation
4. Describe with specific examples the regulation of complement activation
5. Explain the ESSENTIAL differences between the classical and the alternative complement activation pathways
6. Discuss why the amplification phase in critical to many immune reactions.
7. Specify the major sources of complement and comment on the genetic control of complemt proteins

SHORT ANSWER QUESTIONS

1. Complement is involved in antigen-antibody interactions, yet there is no agglutination or precipitation.
2. What does happen?
3. What are the important functions of complement?
4. If complement activation can lead to lysis of antibody tagged cellular antigens, what is the purpose of complement activation by antibody-tagged non cellular antigens?
5. Differentiate between the classical pathway and the alternate pathway of complement activation
6. Briefly discuss the three stages of the classical pathway of complement activation. What stage is the most important? Why?
7. What is the difference between complement activation by antigen-IgM complexes and antigen-IgG complexes?
8. What is the biologic importance of C4a?
9. What complement components make up C3 convertase and what does it do?
10. Macrophages have receptors for C3b. What is the biologic significance of this fact?
11. What is the last complement component to be split into two biologically active fragments? What are their functions?
12. If the complement cascade is stopped before the membrane attack phase, has complement fulfilled its function in an immune response? If Yes, Why? If No? Speculate on the reason for having the membrane attack phase?
13. What components of the complement system are shared between the classical pathway and the alternative pathway?
14. Why is it important to tightly control complement activation?

Leukocyte Migration & Inflammation

ASSIGN READING CHAPTER 15: pp 357-378 OUTLINE/SUMMARY

1. Lymphocyte Recirculation
2. Cell Adhesion Molecules
   • Selectin family
   • Mucin-like family
   • Integrin family
   • Immunoglobulin superfamily
3. Neutrophil Extravasation
4. Lymphocyte Extravasation
   • High endothelial venules
   • Lymphocyte homing
   • naive lymphocytes
   • effector lymphocytes
   • memory lymphocytes
   • Adhesion molecule interactions
5. Mediatiors of Inflammation
   • Chemokines
   • Plasma enzyme mediators
   • kinins
   • clotting system
   • fibrinolytic system
   • complement
6. Lipid inflammatory mediators
7. Cytokine inflammatory mediators
8. Inflammatory Process
9. Role of neutrophils
10. Acute inflammatory response
    • localized response
    • systemic acute phase response
11. Chronic inflammatory response
    • role of IFNs
    • chronic inflammatory diseases
12. Anti-inflammatory Agents
    • Reduction of Leukocyte extravasation
    • corticostroids
    • Nonsteroidal anti inflammatories

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS:

ON COMPLETION OF THIS SECTION THE STUDENT SHOULD BE ABLE TO:

1. Describe lymphocyte recirculation
2. Describe four classes of cell adhesion molecules
3. Describe four sequential but overlapping steps in neutrophil extravasation.
4. Discuss the role of G proteins in neutrophil extravasation.
5. Describe the location, structure and function of High endothelial venules
6. Distinguish between neutrophilic and lymphocytic extravasation
7. Construct a table to compare the C-C subgroup of chemokines with the C-X-C subgroup of chemokines
8. Describe the inflammatory process.
9. Compare the localized acute inflammatory response with the systemic acute phase response.
10. Draw a diagram to give an overview of the cells and mediators involved in a local acute inflammatory response [371]
11. Draw a diagram to give an overview of the cells and mediators involved in a systemic acute inflammatory response [372]
12. Describe the chronic inflmmatroy response [373]
13. List 5 chronic inflammatory diseases associated with HEV [375]
14. Discuss the use of antiinflammatory agents to reduce long term inflammatory responses in infections, transplants and burns.

SHORT ANSWER QUESTIONS

Immune Effector Responses

ASSIGNED READING: CHAPTER 16: pp 379-412 OUTLINE/SUMMARY

1. Effector Responses of Cell Mediated Immunity
   • Properties of effector T cells
   • activation requirements
   • cell adhesion molecules
   • effector molecules
2. Direct cytotoxic responses
   • CTL mediated cytotoxicity
   • NK cell cytotoxicity
   • antibody dependent cell mediated cytotoxicity
   • experimental methods
3. Delayed type hypersensitivity(DTH)
   • phases of DTH response
   • cytokines in DTH
   • protective role
   • detection of DTH
   • pathological responses of DTH
4. Effect Responses of Humoral Immunity
   • Primary & secondary responses
   • Experimental methods
   • hemolytic plaque assay
   • Elispot assay
   • Hapten-carrier conjugates
5. Regulation of Immune Effector Response
   • antigen mediated regulation
   • antibody mediated suppression
   • immune complexes as regulators
   • idiotypic regulation
   • neuroendocrine regulation

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS

ON COMPLETION OF THIS SECTION THE STUDENT SHOULD BE ABLE TO:

1. Define and conceptualize immunological tolerance
2. Describe and experiment that shows tolerance indcution
3. Outline the mechanisms that induce self tolerance

SHORT ANSWER QUESTIONS

1. Briefly discuss the three phases of an immune response.
2. Which phase is most complex and why?
3. In which phase does antigen have little importance and why?
4. What distinguishes humoral immunity from cell mediated immunity?
5. What do we mean by a primary and a secondary immune response?
6. What characteristics usually distinguish the two responses?
7. Briefly discuss the antigen elimination curve.
8. What things affect the shape of the curve and how does this affect antibody production?
9. Briefly describe the four phases of a primary antibody response.
10. When comparing the primary and secondary antibody responses, three things change during the secondary antibody response.
11. What are they?
12. Which one do you consider the most important? Why?
13. Early experiments showing the importance of lymphocytes to immunity followed two approaches.
14. What were they?
15. How did they differ?
16. What were some of the initial observations that arose from these two approaches?
17. Describe the carrier effect.
18. How did the study of the carrier effect resolve whether T and B cells needed to react specifically with the same epitope on an antigen molecule, and whether T cells and B cells are specific for distinct antigenic determinants on a complex antigen?
19. Claman and his collegues provided the first direct evidence that, for antibody responses, synergy was required between T cells and B cells.
20. Describe the experiment.
21. Did the experiment show which cell did what? Explain. see the following for details
22. Claman, H. N., E.A. Chaperon and R.F. Triplett (1966) Thymus marrow cell combinations. Synergism in antibody production. Proc. Soc. Exp. Biol Med. 122:1167-1171
23. Two kinds of immune cells are needed for antibody responses.
24. Mitchell and Miller's experiment demonstrated which cell did what. How could they do this experiment if they did not have antibodies specific for the two immune cells?
25. Describe how Mitchison used the idea of the carrier effect to determine whether the interacting T and B cells recognized the same or different epitopes on a complex antigen.
26. Design an experiment proving that B cells recognize the haptenic portion of a hapten carrier complex and that T cells provide help in this interaction.
27. B cells can internalize and process antigen.
28. This fact resolves the following question:
    "How could T helper cells with one receptor for both an antigen fragment and an MHC-II molecule on the surface of a macrophage provide antigen-specific help to a B cell bearing antigen in its antibody receptor?"
29. How do macrophages contribute to antibody production?
30. How can the mixed lymphocyte reaction and the cytotoxicity reaction be used to explain how T cells help other T cells and which cell provides help and which cell mediates cytotoxicity?
31. Helper T cells can be divided into two subsets based on their lymphokine secretion profile. Explain.
32. As an immune response progesses, it needs to limit itself and decrease in intensity. How does antibody feedback accomplish this?
33. Niels Jerne states that "antibodies recognize" and are "being recognized" explain this statement in terms of the network hypothesis.
34. Briefly describe the dowregulatory cross regulation between certain cytokines during the humoral immune response.
35. How does immunodificiency differ from immunotolerance?
36. Design an experiment that shows tha "In utero" or "in ovo" exposure to forein antigens leads to tolerance in the adult animal.
37. The clonal selection theory lends support to the idea of immunologic tolerance. Explain.
38. Briefly discuss some of the conditions that affect the initiation of immunologic tolerance.
39. What is common among these conditions?
40. What are some of the basic differences between an antigen and a tolerogen?
41. Tolerance of self- antigens seems to be permanent, while experimentally induced tolerance is not. Explain.
42. The idea of clonal deletion suggests that self reactive cells are eliminated (no cells to react to self antigens; therefore, we tolerant self antigens), yet autoimmune diseases occur (react to self antigens). Explain.

Hypersensitive Reactions

ASSIGNED READING CHAPTER 17: pp 413-439

OUTLINE/SUMMARY

1. Gell & Coombs Classification
2. Type I Hypersensitivity: IgE mediatiated
   • Components
   • allergens
   • IgE
   • Mast cells & basophils
   • IgE binding receptors
3. Mechanisms
   • receptor cross linkage
   • intracellular events
4. Mediators
   • histamine
   • leukotriens & prostoglandins
   • cytokines
5. Consequences
   • systemic anaphylaxis
   • localized anaphylaxis
   • late phase reaction
6. Regulation
7. Detection
8. Theraphy
9. Type II Hypersensitivity: Antibody mediated cytotoxic
   • Transfusion reactions
   • Hemolytic disease of the newborn
   • Drug induced hemolytic anemia
10. Type II Hypersensitivity: Complex mediated cytotoxic
    • Localized reactions
    • Generalized reactions
    • Type IV Hypersensitivity: DTH mediated

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY WORDS:

ON COMPLETION OF THIS SECTION THE STUDENT SHOULD BE ABLE TO:

1. List the Gell & Coombs classification for hypersensitivity reactions; give examples of each type.
2. Describe stimulatory hypersensitivity and give a specific example
3. Discuss the difference between primary and secondary exposure to antigen in imunity and in hypersensitivity
4. Describe the structural and functional characteristics of IgE.
5. Discuss the cytotropic nature of IgE
6. Differentiate betweeen the cyclooxygenase and lipoxygenase pathways of mediator production
7. Describe the role of mast cells in immediate hypersensitivity reactions.
8. Distinguish between release of preformed and newly formed mediators from mast cells and give examples of each type of mediator
9. Discuss the hallmarks of delayed type hypersensitivity
10. Explain the mechanisms of Delayed Type Hypersensitivity induction and development
11. Distinguish between different types of Delayed type hypersensitivity.
12. Describe tuberculosis in terms of hypersensitivity reactions.

SHORT ANSWER QUESTIONS

1. By derivation, what does allergy mean and what does hypersensitivity mean? Are they synonymous?
2. The main difference between immediate and delayed types of hypersensivitiy is the time of appearance of the reactions. True/False? If false, name the main differences.
3. What is the type II reaction described by Gell & Cooombs? Does this reaction require complement?
4. Is there a tendency to immediate hypersenstivity reactions? Explain?
5. Differentiate between antigen and allergen.
6. What immune and nonimmune cells are involved in immediate hypersensivity?
7. What class of antibody in responsible for immediate hypersenstivity?
8. Describe some structural and biological characteristics of this antibody?
9. What do we mean by homocytotropic antibodies?
10. Briefly describe the result of the interaction of IgE, with mast cells
    • in the presence of allergen.
    • in the absence of allergen.
11. What are the chemical mediators of immediate hypersentivity reactions?
12. Some effector molecules of immediate hypersensitivity reactions are preformed mediators; others are newly synthesized mediators.
13. Distinguish between the two.
14. Briefly describe the two pathways for the production of newly synthesized mediators.
15. How can you determine whether a person is allergic to a foreign protein?
16. What is the triple response?
17. Name two "in vitro" test. W
18. hat is the mechanism for desensitization for immediate hypersensitivities?
19. Is this desensitization lifelong?
20. If not speculate on the reasons.
21. What are some other modes of treatment for immediate hypersensitivity?
22. Describe the differences between systemic anahylaxis and atopy?
23. Are the mechanisms of cell-mediated immunity and DTH the same?
24. Name the effector cells in DTH.
25. What are some of the hallmarks of DTH reactions?
26. Describe contact sensitivity.
27. How does contact sensitivity differ from the tuberculin skin reaction?
28. What is the mechanism of the tuberculin skin test?
29. If the test is positive what causes the induration (hardening) of the test site?
30. What substances are used in this test?
31. Name three different types of tuberculin skin tests?