Immunology Course Outline/Summary

For Campus Course
updated 16/09/02

General Info Deadlines Grade Distribution Midterm Exams Sample Exam Final Exam Lecture Sequence Lab Sequence

IMMUNOLOGICAL TOLERANCE (How to survive your first course in immunology)
Immunology is an exciting and challenging field with theoretical and practical applications. For many students, the challenge of immunology can be intimidating yet it need not be. Like many areas in biology it builds steadily from simple beginnings. If you learn not only the facts, vocabulary and concepts of immunology, but also master the problem solving process, you will be able to apply these ideas to new problems. This is the true adventure of immunology; "To boldly go where no one has gone before".

Mastery of the problem solving process improves with practice. Fortunately, you need not practice alone. Use your friends, colleagues, teaching assistants and professors as foils to develop you skills. Professor Tom Carney calls this "Liberation Learning" the true function of the university.

While the facts and vocabulary of immunology can be learned in a few "all-nighters", mastery of the concepts and processes takes time, so start early.

"Go Forth and Prosper"

General Info

UPDATED May  24,2002

COURSE INFORMATION PREREQUISITES 55-140, 55-141

COREQUISITE 59-230

COURSE DESCRIPTION A study of antibody formation, the structure of antibodies and antigens and the mechanisms of antigen-antibody interactions

LECTURES Mon/Wed/Fri 12:30-1:20 Room 264 Dillon Hall

LABORATORY Mon,Tues, Fri 2:30- 5:20 Room 303, 305 Biology Building

INSTRUCTOR Professor Hugh B. Fackrell Room 320 Biology Building Office 253-4232 ext 2705

TEXTBOOK Kuby Immunology 4th Ed W.H. Freeman, New York

EXAMINATION DATES The dates for the mid term and lab exams are tentative. The class may reset the dates to accommodate other courses. However change of an examination date will require approval of a majority of the class and 10 days notice.

CONSULTING HOURS I will be available in BB 313 from 8:00-9:30 AM Mon, Wed, & Fri in addition to being in labs during the regular lab periods. I have an open door policy and the coffee pot is always on so feel free to drop by.

WEBSITE A Website for the course contains all the lecture presentation material, extensive detailed textual information for reference, Performance Objectives, and question databanks.

The Website is Password protected. The passwords are given during the first class

Deadlines For  Campus Course

Sept 6 Classes Begin
Sept 19 Last day for registration
Oct 8 Thanksgiving
Oct 15 MIDTERM EXAM 20%
Oct 31 Last day of partial refund
Oct 31 Last day for voluntary withdrawal
Nov 16 MIDTERM EXAM 20%
Dec 5 Last day of classes
Dec 7 FINAL EXAMINATION 30%

Grade Distribution For Campus Course

GRADE DISTRIBUTION

Exam Date Time Place Value
Midterm 1 Oct 15 12:30-1:20   20%
Midterm 2 Nov 16 12:30-1:20   20%
Lab Projects Every 2 weeks   2:30 BB305 30%
Final Exam Dec 7 12:00-3:00 PM TBA 30%

GRADE EQUIVALENTS

A+(95), A (85), A- (80) Excellent
B+(77) B (74) B- (70) Good
C+(67) C (64) C- (60) Fair
D+(57) D (54) D- (50) Pass
F (42) F-(22)   No Credit
Inc     Incomplete (becomes an F after 6 weeks)
NR     No Report

MARK CONVERSION TABLE

MARK GRADE MARK GRADE MARK GRADE
0-35.99 F- 36-49 F    
50-53.99 D- 54-56.99 D 57-59.99 D+
60-63.99 C- 64-66.99 C 67-69.99 C+
70-73.99 B- 74-76.99 B 77-79.99 B+
80-84.99 A- 85-94.99 A 95-100 A+

Class marks will not be scaled or curved

Missed Exams or Reports

Missed exams or reports will be assigned a mark of 0

If either the 1st or 2nd Midterm examination is missed for a legitimate reason (ie university business, illness or compassionate grounds) then the examination will be prorated.

 

Mid Term Exams Campus Course

Examinations will be constructed DIRECTLY from the Performance Objectives and the Self Evaluation Questions.

A databank of all the questions is availableon the website.

Examinations will be a combination of objective,short essay questions, problems, diagrams and tables.

Answers will be evaluated on organization, pertinence and clarity as well as factual content.

Representative answers will be posted on the Website.

Midterm 1 on Oct 15 at 12:30-1:20 in will exam the material covered from Sept 6 to Oct 8 inclusively.
Midterm 2 on Nov 16 at 12:30-1:20 in will exam the material covered from Oct15 to Nov 10 inclusively.

Each midterm examination will concern the information covered since the previous examination.

Grades will NOT be posted on the Website

Exams will be remarked when requested in writing with specific reasons. A request for a remark means that the marking was flawed and the entire exam will be remarked. An remarked exam may have a similar, higher or lower grade than the original. The remarked grade replaces the original grade.

Sample Exam

55-242 Immunology Midterm examination

Length: 50 min Date........... Student name........... Student number..........

IMPORTANT!!! This examination will NOT be marked if this registration is not signed

General Instructions: No study materials, notes, calculators, or textbooks are allowed in the examination room. Examination proctors are not permitted to provide any help with the questions. Examination proctors will ask you to provide proper identification . Examination proctors have the right to select your seating position in the examination room and to change your seating position during the course of the examination. Examination proctors have the right to replace your examination materials during the course of the examination. Replacement of examination materials will only occur under exceptional circumstances such as errors in the exam materials, disaster, illness, washroom breaks, or suspected cheating. If replacement of examination materials occurs, DO NOT START OVER BUT CONTINUE THE EXAMINATION ON REPLACEMENT COPY. Answer the questions to the best of your ability. Answer the questions ONLY in the space provided. Information that you provide outside the allotted space will not be marked.

I have read the above general instructions and agree to comply with them

Student Signature........................................

Part A: Multiple Choice Questions These questions are taken directly from the on line interactive multiple choice quizzes which are found in the Self Evaluation Section of each topic

Question 1-15: Multiple Choice Questions The 15 multiple choice questions are worth 2 marks each.

Part B: Definitions Theses are taken directly from the lists of definitions provided under the Performance Objectives for each topic

Question 16 Each of the definitions is worth 3 marks Define the following terms in sentence form:

Part C: Short Answer Questions

These short answer questions are derived directly from the Performance Objectives and the Self Evaluation Sections of each topic.

Question 17: (20 marks) In the space provided, construct a table comparing the biological characteristics of the five classes of immunoglobulins

Question 18: (10 marks) Describe and Draw MHC-II molecules

Question 19: (10 marks) Describe the V-J joining for light chain genes in terms of the 7-9 and the 12-23 rules

Final Exam

FINAL EXAMINATION (30%) The final examination is a 3 hour examination that covers the entire course material from labortories, lectures, and textbook.

The final Examination will be constructed DIRECTLY from the Performance Objectives and the Self Evaluation Questions for the entire course.

Answers will be evaluated on organization, pertinence and clarity as well as factual content.

Lecture Sequence

Topic # Chapter Assigned Reading 4th Ed Assigned Reading 3rd Ed
01 Background & History Ch 1 Ch 1
02 Innate Immunity  Ch 1 Ch 1
03 Acquired Immunity Ch 1 Ch 1
04 Cells and Organs of the Immune System Ch 2 ch 3
05 Antigens Ch 3 Ch 4
06 MHC Ch 7 Ch 9
07 Antigen Processing and Presentation Ch 8 Ch 10
08 Immunoglobulins: Structure & Function Ch 4 Ch 5
09 T-cell Receptor Ch 9 Ch 11
10 Organization and Expression of Immunoglobulin genes Ch 5 Ch 7
11 Antigen-Antibody Interactions Ch 6 Ch 6
12 B cell Maturation, Activation & Differentiation Ch 11 Ch 9
13 T cell Maturation, Activation & differentation Ch 10 Ch 12
14 Complement Ch 13 Ch 14
15 Cytokines Ch 12 Ch 13
16 Hypersensitivity Reactions Ch 16 Ch 17
17 Leukocyte Migration and Inflammation Ch 15 Ch 15
18 Cell mediated and Humoral Effector Responses Ch 14 Ch 16
19 Vaccines Ch 18 Ch 18
20 The Immune System in AIDS Ch 19 Ch-22
21 Autoimmunity Ch 20 Ch 20
22 Immunodeficiency diseases Ch 17 Ch 21
23 Transplantation Immunology Ch 21 Ch 23
24 Cancer and the Immune System Ch 22 Ch 24

 

NOTES: Topic #:= number on the Website Assigned Reading: J. Kuby 4th Ed Immunology

Laboratory Sequence


LABORATORY SEQUENCE

LAB TOPIC
1 Cells of the Immune System
2 Tissues and Organs of the Immune System
3 Antigenic Epitopes: Humoral Immunity
4 Antigenic Epitopes: Cell Mediated Immunity
5 ImmunoAssays: Precipitin Reactions
6 ImmunoAssays: ELISA

LABORATORY REPORTS Six (6) lab reports are required. Each report is worth 5%

MISSED REPORTS IF A LABORATORY REPORT IS MISSED FOR A VALID REASON, (MEDICAL, COMPASSIONATE OR UNIVERSITY BUSINESS), THE FINAL GRADE WILL BE PRORATED. OTHERWISE A MARK OF ZERO (0) WILL BE GIVEN FOR A MISSED GRADE.

Overview of Immunity

ASSIGNED READING

CHAPTER 1 pp 3-24
Innate immunity I6-11
Phagocytosis 65,68,467
Phagocytic deficiences  
Inflammation 357, 369-377
Complement 348-353
Lysozyme 8, 10
Interferon (INF) 460-461, 590-591, 373-375
Tumour necrosis factor (TNF) 370-375
NK Cells 387-390
NK Cells and TNF 391
Phagocytic deficiencies 507-511

 

OUTLINE/SUMMARY

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY WORDS:

Innate immunity non specific immunity lysozyme
interferon complement phagocytes
monocytes neutrophils natural killer (NK) cells
Null cells, chemotaxis diapedesis
phagocytosis primary exposure secondary exposure
mmunological memory    

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

  1. Appreciate three functions of the immune system
  2. Distinguish between innate immunity and acquired immunity
  3. Discuss how thew clonal selective theory explains the immune systems's
  4. ability to recognize millions of antigens
  5. Describe the basic structural and functional components of the immune system

SHORT ANSWER QUESTIONS

  1. One of the functions of the immune system is surveillance. What can happen to the host if surveillance is naturally or artificially suppressed?
  2. How does clonal selection explain antibody diversity, antibody specificity and immunologic memory?
  3. Why was the discovery of DNA structure important in describing the development of humoral immunity?
  4. Differentiate between cell mediated and humoral immunity.
  5. LIST the cellular components required for a completed immune system.
  6. Why are humans resistant to many animal diseases; for example canine distemper, feline leukemia, and cowpox?
  7. Differentiate and discuss the characteristics of innate immunity from those of acquired immunity.
  8. Differentiate between variolation and vaccination.
  9. Why is active immunity better than passive immunity?
  10. We exist in a preimmune state. Explain.

Experimental Systems

CHAPTER 2 IS BACKGROUND READING ONLY !!!!

Organs of the Immune System

ASSIGNED READING CHAPTER 3: pp 47-83
OUTLINE/SUMMARY

  1. Hematopoiesis
  2. Immune System Cells
  3. Organs of the Immune System

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS:

Accessory cells activated macrophages Antibody depentdent cell mediated cytotoxicity (ADCC)
ntigen presenting cells (AAPCs) B cell Bone marrow
Bursa of Fabricius Cytotoxic T cells Dendritic cells
germinal centre Helper T cells hematopoiesis
monocytes lymphocytes High endothelial venules (HEVs)
Lymph node: lymphoid organs Large granular lymphocytes
natural killer cells plasma cells lymphoid system macrophages
primary follicles (nodules) secondary follicles mucoals associated lymphoid tissuse (MALT)
primary lymphoid organs T lymphocytes thymic hormones,
secondary lymphoid organs cortex Thymus dependent area
High endothelial venules Spleen thymus independent area
marginal zone afferent lymph vessels periarteriolar lymphoid sheath (PALS
medulla paracortex efferent lymph vessels
red pulp white pulp trabeculae
Thymus medulla  

 

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

  1. Describe the life history of leukocytes
  2. Construct a table to compare and contrast B Lymphocytes and T lymphocytes with respect to structures, roles in immunity, origin, maturation and location
  3. Differentiate among helper T cells, Cytotoxic T cells and regulatory T cells
  4. Describe macrophages in terms of ther origin, location and nomenclature
  5. Describe the role of macrophages in immunity
  6. Describe the role of dendritic cells
  7. Describe the characteristics of NK (Null cells)
  8. Describe the role of NK cells (Null cells) in Immunity
  9. Locate the different types of lymphoid tissues in the body
  10. Differentiate betweeen primary and secondary lymphoid organs
  11. Differentiates between bone marrow and thymus
  12. Differentiate among lymph nodes, spleen and MALT
  13. Compare the Bursa of Fabricius with Peyer's Patches
  14. Draw and label diagrams of the structure of the thymus, lymph node, and spleen
  15. Interpret the role of the thymus in the establishment of the immune system in the body.

SHORT ANSWER QUESTIONS

  1. Although the immune system has B cell and T cells, the statement has been made " no T cells, no immunity". Explain.
  2. Compare how null cells and cytotoxic T cells kill their targets.
  3. Briefly describe the specific roles of helper and cytotoxic T cells in normal immunity. Correlate these roles with CD4+ T cells and CD8+ T cells.
  4. Unlike B cells and T cells, macrophages are neither clonally restricted nor antigen specific. Explain. Differentiate between primary and secondary lymphoid.
  5. Name four morphological areas of the lymph node and give the cellular composition of each.
  6. Which area of the lymph node is called the thymus independent area? Why?
  7. Which area of the lymph node is called the thymus dependent area? Why?
  8. Describe T cell differentiation in the thymus using CD4 and CD8 markers.

Antigens

ASSIGNED READING CHAPTER: 4 pp 87-106
OUTLINE/SUMMARY

  1. Immunogenicity vs antigenicity
  2. Factors that influences immunogenicity
  3. Epitopes
  4. Haptens
  5. Mitogens

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS

Accessibility antigen antigenic determinants
antigenic site mobility antigenicity agreotopes
continous (linear) determinants) epitopes haptens
discontinous(conformational) determinants immunogen immunodominance
immunogenicity    

 

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

  1. Differentiate between and antigen's inductive and reactive abilities.
  2. Explain the factors that bestow immunogenicity on molecules
  3. Describe the discrete and distinctive sites on and antigen that are recognized by a B cell
  4. Immunoglobulin
  5. Describe the discrete and distinctive sites on and antigen that are recognized by a T cell receptor
  6. Describe the discrete and distinctive sites on and antigen that are recognized by the Major
  7. Histocompatability Complex
  8. Discuss some important characteristics of protein antigenic determinants

SHORT ANSWER QUESTIONS

  1. Differentiate between immunogenicity and antigenicity.
  2. All immunogens are antigens but all antigens are not immunogens. Explain with the use of specific examples.
  3. An entire microbe or molecule does not induce and immune response. Explain.
  4. Irrespective of the number of epitopes that a molecule has, the immune response is biased and sees what it wants to see. Explain.
  5. Haptens are usually coupled to a carrier molecule before they are immunogenic. How can you demonstrate that the selected immunoglobulins are specific for the hapten and not for the carrier? As a corollory, would you expect ALL of the antibodies to be specific for the hapten? explain.
  6. Why is the definition of an antigen considered to be an operational definition.
  7. Differentiate between epitopes and agreotopes.
  8. Differentiate between epitopes recognized by B cell receptor and epitopes recognized by T cell receptors.

Immunoglobulin Structure & Function

ASSIGNED READING CHAPTER 5: pp 107-142
OUTLINE/SUMMARY

  1. Basic Structure
  2. Immunoglobulin Sequencing Studies
  3. Immunoglobulin Fine Structure
  4. B Cell Receptor
  5. Antigenic Determinants of Igs
  6. Ig Classes
  7. Immunoglobulin Superfamily
  8. Monoclonal Antibodies (MABS)

PERFORMANCE OBJECTIVES

 

DEFINE THE FOLLOWING KEY TERMS:

allotypes allotypic determinants Am determinants
Gm determinants Km determinants Bence Jones proteins
Antibodies immunoglobulin classes antibody subclasses
Fab fragment constant region (C Fab' fragment
F(ab')2 fragment Framework residues (FR) Fc fragment
Heavy chain hinge regions chimeric antibodies
hybridoma hypervariable regions (HVRs) idiotypic determinants
idiotypes complematrarity determining regions(CDRs) variable regions (V)
immunoglobulins Hypoxantinine-Aminoopterin-Thymidine medium (HAT) immunoglobulin domains
isotype isotypic determinants joining chain (J)
Light chain monoclonal antibodies, multiple myeloma
Secretory IgA Segmental flexibility  

 

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

  1. Distinguish between the overall structure and the fine structure of immunoglobulins
  2. Describe the variable and constant regions of immunoglobulins light and heavy chains
  3. Explain the structural organization of the variable regions of an immunoglobulins light and heavy chains
  4. Differentiate between Hypervariable regions and complementarity determining regions
  5. Contrast monoclonal antibody production vs polyclonal antibody production
  6. Discuss the differences in the biological effector functions of the different classes of immunoglobulins
  7. Diagram the procedure for monoclonal antibody production
  8. Construct a table comparing the biological characteristics of the five classes of immunoglobulins
  9. Construct a table comparing the biochemical and biophysical characteristics of the five classes of immunoglobulins

SHORT ANSWER QUESTIONS

  1. The analysis of IgG molecules after hydrolysis by pepsin and papain led to similar yet different results. Explain.
  2. What is the difference between and immunoglobulin and a myeloma protein?
  3. Why were myeloma proteins and Bence Jones proteins critical to the early studies on antibody structure? What has largely replaced them?
  4. Differentiate among, complementarity determining regions, hypervariable regions and framework regions.
  5. Explain the statements:
  6. Discuss the terms immunoglobulin isotypes, immunoglobulin allotypes and immunoglobulin idiotypes and give examples of each.
  7. Compare conventional antibody production with monocloanl antibody production and recombinant antibody production.
  8. What are antibody domains?
  9. Why can't light chains be used to classify antibodies?
  10. The function of an immunoglobulin molecule is related to its structure. Explain.
  11. Different cellular fusion products can potentially occur in a hybridoma fusion.
  12. Distinguish between idiotypes and anti-idiotypes.

Antigen-Antibody Interactions

ASSIGNED READING CHAPTER 6: pp 144-164
OUTLINE/SUMMARY

  1. Strength of Antigen-Antibody Interactions
  2. Cross Reactivity
  3. Precipitin Reactions
  4. Agglutination Reactions
  5. Radioimmunoassay (RIA)
  6. Enzyme Linked Immunosorbent Assay (ELISA)
  7. Western Blots
  8. Immunofluorescence
  9. Immunoelectron Microscopy

PERFORMANCE OBJECTIVES

 

DEFINE THE FOLLOWING KEY TERMS

agglutination direct agglutination reaction indirect agglutination reaction
antibody affinity association constant (K) average affinity
antiserum verage intrinsic association constant(Ka) avidity
ELISA equilibrium constant equilibrium dialysis
fluorescein fluorochromes hemagglutination
passive hemagglutination passive hemagglutination inhibition immune precipitation
immunofluorescence reverse passive hemagglutination ring test
Ouchterlony methods immunoelectrophoresis Indirect fluorecent antibody test
plasma primary antigen-antibody interactions Radioimmunoassay
Rhodamine secondary antigen-antibody interactions serology
serum titer zone phenomena
antibody excess antigen excess equivalence

 

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

  1. Explain a primary antigen-antibody interaction and include at least three important charactistics
  2. Describe the forces that encourage primary antigen-Antibody interactions
  3. Distinguish betweeen antibody affinity and avidiy.
  4. Describe the strength of the primary antigen-Antibody interactions using equilibrium dialysis. Include the terms K and Ka
  5. Compare and contrast RIA and ELISA
  6. Describe direct and indirect fluorescent antibody methods.
  7. Describe a secondary antigen-antibody interaction in terms of lattice formation and antigen:antibody ratios.
  8. Explain zone phenomena.
  9. Construct a table to compare the various procedures used to determine the presence of solbule antigen or antibody in a fluid and in a gel.
  10. Assess the reasons for using the different gel preciptitin reactions
  11. Distinguish between agglutination and preciptin reactions and give the advantages and disadvantages of each.

SHORT ANSWER QUESTIONS

  1. Cross reactivity of antibodies creates problems for their application in serology. Explain.
  2. Differentiate between a primary and a secondary antigen-antibody reaction. What are three important characteristics that distinguish the two reactions?
  3. What kinds of noncovalent interactions are important in antigen-antibody interactions? What aspect of these interactions is most important and why?
  4. How is equilibrium dialysis used to measure PRIMARY antigen-antibody reactions?
  5. Differentiate between avidity and affinity.
  6. Discuss the term lattice formation.
  7. What are the pros and cons of RIA?
  8. Describe two types of immunofluorescence tests.
  9. What is the advantages of the indirect procedure over the direct procedure?
  10. What are some commonly used fluors?
  11. What colour does each fluor emit?
  12. What makes precipitin reactions visible?
  13. What two factors are important in the development of precipitin reactions?
  14. Three patterns can be observed in the Ouchterlony test.
  15. DRAW and LABEL diagrams to illustrate these patterns.
  16. What does each pattern show?
  17. What is the major advantage of immunoelectrophoresis over immunodiffusion?
  18. What are the disadvantages?
  19. How does agglutination differ from precipitation?
  20. Why are agglutinatin tests more sensitive that precipitin tests?
  21. Differentiate between direct and indirect agglutination reactions?
  22. What is a major advantage of indirect agglutination reaction over direct reactions?

Immunoglobulin Genes

ASSIGNED READING CHAPTER 7: pp 165-194

OUTLINE/SUMMARY

  1. Genetic models
  2. Multigene Organization of Immunoglobulin Genes
  3. Variable-Region Gene Rearrangements
  4. Generation of Antibody Diversity
  5. Class Switching in C Region Genes

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS:

allelic exclusion class switching combinatorial freedom of chain association
Constant (c) gene segments Diversity (D) gene segements comibinatorial association of gene segments
Palindromes acceptor junctions donor junctions
enhancers exons 7-9 rule
12-23 rule Germline theory somatic theory
mprecise DNA rerangement introns Insertion of random N regions
Joining (J) gene segments junctional diversity leader sequence
Membrane (M) exons n regions promotors
recognition sequences spacer sequences somatic hypermutation
switch recombination switch (S) regions variable(V) gene segments

 

 

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

  1. Describe how the number and organization of immunoglobulin gene segements or exons contribute to the generation of antibody diversity
  2. Draw the organization of Kappa light chain genes.
  3. Draw the organization of Lambda light chain genes.
  4. Draw the organization of heavy chain genes.
  5. Describe the V-J joining for light chain genes in terms of the 7-9 and the 12-23 rules
  6. Describe the V-D-J joining of heavy chain genes in terms of the 7-9 and the 12-23 rules.
  7. Explain how allelic exclusion leads to cells that produce immunoglobulins with a single antigen binding site.
  8. Describe how transcription controls immunoglobulin gene expression
  9. Describe at least four mechanisms that contribute to antibody diversity
  10. Describe the coexpression of IgM and IdD in terms of RNA processsing
  11. Describe the mechanisms for class switching
  12. Correlate B cell differentiation with immunoglobulin gene rearrangements

SHORT ANSWER QUESTIONS

  1. Why is it important to have antibody diversity?
  2. Differentiate between the germline theory and the somatic theory of generation of antibody diversity.
  3. How are BOTH germline and somatic mechanisms sources of antibdoy diversity?
  4. Why did the amino acid sequencing of antibody light chains lead Dryer and Bennet to abandon the one gene- one polypeptide theory and propose that two genes code for a single polypeptide?
  5. Describe Tonagawa's approach to answering Dreyer and Bennett's hypothesis that two genes code for a single polypeptide.
  6. In addition to showing that DNA seqments come together to form a functional antidoby gene, Tonagawa's experiments showed two other things. What were they?
  7. The phrases "race car", "Madam I am Adam" and "sex at noon taxes" represent pallindromes in the english language. What are pallindromes in the genetic code and what is their importance in V region construction?
  8. What are the two DNA recombinational events required to assemble a functional heavy chain V region gene?
  9. The two DNA recombinational events required to assemble a functional heavy chain V region gene, are governed by the 7-9 and the 12-23 rules. Explain.
  10. Discuss four mechanisms that contribute to antibody diversity.
  11. Describe the differential splicing of RNA that progresses from membrane bound IgM to secreted IgM.
  12. Explain how a particular B cell can secrete different antibody isotypes, yet remain specific for the same epitope.
  13. What are the two stages of class switching?
  14. Dicuss allelic exclusion; what it is and how it is regulated.
  15. List in correct chronological order the events leading to the synthesis of a Kappa light chain and its incorporation into an antibody molecule.
  16. List in correct chronological order the events leading to the synthesis of a Gamma chain and its incorporation into an antibody molecule.

B Cell Maturation

ASSIGNED READING Chap 8 pp 195-222

OUTLINE/SUMMARY

  1. B Cell Maturation
  2. B Cell Activation & Proliferation
  3. In Vivo induction of Humoral Response
  4. B Cell Differentation
  5. Regulation of B Cell Development

PERFORMANCE OBJECTIVES

 

DEFINE THE FOLLOWING KEY TERMS:

affinity maturation apoptosis avidity
capping carrier effect cell mediated immunity
Cytotoxic T cells Helper T cells TH1 cells
TH2 cells humoral immunity immunologic memory
perforin plasma cells primary antibody
programmed cell death secondary antibody thymus dependent antigens
thymus independent antigens    

 

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

  1. Describe the sequential development of the humoral immune response.
  2. Draw a contemporary model for T cell B cell macrophage interaction
  3. Describe antigen processing and presentation by B cells
  4. Outline the sequence of helper (T/(TH) cell involvment in antibody production
  5. Describe the interplay between TH1 and Th2 cells in the development of immune responses

QUESTIONS

Major Histocompatability Complex

ASSIGNED READING CHAPTER 9:pp 223-248

OUTLINE/SUMMARY

  1. General Organization of MHC
  2. MHC Molecules & Genes
  3. Genomic maps of MHC
  4. Cellular Distribution of MHC
  5. Regulation of MHC Expression
  6. MHC and Immune Responsiveness

OBJECTIVES

 

DEFINE THE FOLLOWING KEY TERMS

alleles alloantigens bone marrow chimeras
Class I molecules Class I regions Class II molecules
Class II regions Class III molecules Class III regions
Determinant selection model H-2 complex K region
D region I region L region
S region hole in the repertoire locus
immune response genes congenic mice Human Leukocyte Antigens
Major histocompatibility complex MHC restriction, negative thymic selection
positive thymic selection public specificities private specificities
region Specificities superantigens.

 

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

  1. Explain the connection between a trait and a gene using the specific example that MHC genes encode for molecules that allow specific immune responses.
  2. Describe the use of inbred mice for the elucidation of the genetics of the imune response
  3. Describe how congenic strains of mice are developed.
  4. Describe and draw MHC-I molecules
  5. Describe the function of MHC-I molecules
  6. Describe and Draw MHC-II molecules
  7. Compare the detailed differences in the structure of the aggreotope binding sites of MHC-I and MHC-II
  8. Describe the function of class III genes and in which cells they are expressed.
  9. Describe MHC restriction
  10. Discuss the differences between MHC restriction of CD4+ T cells and MHC restriction of CD8+ T cells.
  11. Draw maps of either the MHC gene complex in mice or HLA gene complex in humans
  12. Describe how the collection of MHC genes of an individual dictates either the ability or inability of the animal to respond to a particular antigen
  13. Describe an experiment that shows MHC restriction: between T and B cells, between T cells and macrophages between cytotoxic T cells and virally infected cells.
  14. Discuss the biological relevance of MHC molecules
  15. MHC molecules exhibit a range of structural diversity at the species level that is roughly equivalent to the range of antibody diversity at the level of the individual animal. DISCUSS

SHORT ANSWER QUESTIONS

  1. Null cells are not MHC restricted. Explain.
  2. Even though the immune system rejects transplanted kidneys and hearts its
  3. function is not to protect us against grafts.
  4. Why do we need histocompatability antigens?
  5. If we do not need protection against attack from foreign organs and tissues, why are MHC-I molecules so polymorphic?
  6. What is the connection between immunity and MHC genes.?
  7. Why are inbread/congenic mice important to immunlogical studies?
  8. Draw and label a diagram of a class I MHC molecule as it is found in the membrane.
  9. Draw and label a diagram of a class II MHC molecule as it is found in the membrane.
  10. How is the polymorphism or diversity of MHC, different from the generation of diversity in antibodies?
  11. How do MHC-II molecules allow immune cells to communicate with each other? Why is this communication important?
  12. What is the relationship between MHC-II molecules and Ir genes?
  13. Class III MHC molecules are not cell membrane proteins.
  14. What are they and what do they do?
  15. Describe an experiment to show MHC restricted cytotoxicity
  16. T-cells do not recognize free antigen, as antibody receptors do. Speculate why?
  17. Briefly discuss MHC restriction.
  18. Describe and experiment that describes MHC restriction.
  19. Why do T cells have such an elaborate way of reacting with antigen?
  20. Explain the following statement:
  21. "There is a direct relationship between an animal's MHC haplotype and its ability or inability to respond to a specific antigen."
  22. What is the difference between and F1 hybrid animal and a bone marrow chimera animal?
  23. What is the importance of a bone marrow chimera animal in immunological studies?
  24. Explain how the control of MHC restriction is the genetic basis for the functional specificity of T cells.
  25. Describe T cell differentiation in the thymus using CD4 and CD8 markers.
  26. T cell receptor diversity results from gene rearrangements, but T cells are also MHC restricted. MHC restriction is not preporgrammed into T cells. Describe two possible selective processes that program T cells to be MHC restricted. Where do these processes occur?
  27. T cells can react only with protein fragments. What is this process called? How does it occur? Which pathway leads to antigen interaction with MHC-I molecules? Which pathway leads to interaction with MHC-II molecules?

Antigen Processing

ASSIGNED READING Chapter 10: pp 249-262

OUTLINE/SUMMARY

  1. Self MHC Restriction of T Cells
  2. Role of Antigen Presenting Cells
  3. Two Presentation Pathways
  4. Cytosolic Pathway: Endogenous Antigens
  5. Endocytic Pathway: Exogenous Antigens
  6. Clinical Applications

OBJECTIVES

 

DEFINE THE FOLLOWING KEY TERMS:

antigen presenting cells[253] cytosolic pathway[255] endocytic pathway[258]
professional antigen presenting cells[253] ubiquitin [255] proteosome[255]
nonprofessional antigen presenting cells[253] calnexin[ 257] invariant (Ii) chain [258]
Transportors associated with antigen processing (TAP) [256] CLIP [259] molecular chaperones[257]

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

  1. Describe self MHC restriction.
  2. Compare the cytosolic pathway for antigen presentation with the endocytic pathway for antigen presentation
  3. Compare profession with non professional antigen presenting cells.
  4. Draw a flow diagram comparing cytosolic and endocytic pathways for processing antigens [Fig 10-4]
  5. Describe peptide generation by proteasomes.
  6. Describe transport of antigenic peptides from the cytosol to the Rough Endoplasmic reticulum
  7. Draw a concept map for the separate antigen presenting pathways for endogenous and exogenous antigens.
  8. Describe the assembly of MHC-II molecules within the Rough endoplasmic reticulum.
  9. Describe the development of a viral vaccine that uses the cytosolic pathway.
  10. Describe the development of a vaccine that used the endocytic pathway.

SHORT ANSWER QUESTIONS

  1. Name thee types of professional APCs.
  2. For each type indicate whether it expresses MHC-II molecules and a co-stimulatory signal constitutively or must be activated before doing so.
  3. Describe the role of ubiquitin in the processing of endogenous antigens.
  4. Describe the role of calnexin in the assembly of MHC-I.
  5. T cells can react only with protein fragments.

T Cell Receptor

ASSIGNED READING CHAPTER 11: pp 264-283

OUTLINE/SUMMARY

  1. Early Studies
  2. Structure of T cell Receptors
  3. TCR Genes
  4. T Cell Receptor Complex
  5. TCR-Peptide-MHC Complex
  6. Alloreactivity of T Cells

OBJECTIVES

 

DEFINE THE FOLLOWING TERMS

CD2 CD4 CD8
CD28 CD54 CD58
integrins T cell receptors alpha beta TCR
gamma delta TCR Transcription factor NF-KB  

 

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

  1. Draw the structure of the T Cell Receptor (TCR)
  2. Compare and constrast the structure of TCR with B cell receptor
  3. Draw a diagram of the T cell receptor gene organization
  4. Describe the stragetgies for diversification of T Cell Receptors
  5. Describe how a T cell Receptor recognizes an antigen
  6. Describe the TCR-Antigen-MHC complex

QUESTIONS

  1. Hedrick and Davis used the technique of subtractive hybridization to isolate cDNA clones encoding for the T cell receptor.
  2. Briefly explain the method of subtractive hybridization.
  3. State why this method was so important in the characterization of the TCR.
  4. What does it mean to say that TCRs belong to the Ig supergene family? Briefly describe the heterodimeric structure of the TCR.
  5. TCR genes use the same strategies as antibody genes to develop receptor diversity; however, TCR genes do not exhibit somatic hypermutation. Why?
  6. The TCR is closely assoicated with another surface protein compolex. What is its name and function?
  7. Describe the three way complex that occurs during antigenic recognition by T cells.
  8. T cells can react only with protein fragments.
  9. What are accessory molecules?
  10. Give some examples.
  11. briefly discuss how they may be involved in antigen recognition by T cells.

T cell Maturation

ASSIGNED READING CHAPTER 12: pp 285-310

OUTLINE/SUMMARY

  1. T Cell Maturation
  2. T helper Cell Activation
  3. T Cell Differentiation
  4. Peripherial gamma delta T cells

PERFORMANCE OBJECTIVES

 

DEFINE THE FOLLOWING KEY TERMS:

accessory molecules antigen processing associatve recogonition model
independent recognition model cell adhesion molecules subtractive hybrization

 

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

  1. Outline antigen processing and presentation to TCR
  2. Describe the molecular pathways for T cell activation
  3. Describe positive and negative selection
  4. Discuss the role of accessory molecules in T cell antigen recognition

SHORT ANSWER QUESTIONS

  1. T cell proliferation and differentiation lead to important immunological functions. What are they?
  2. Briefly discuss the molecular events, collected called T-Cell activation, that lead to biologic function.
  3. What is the importance of diacylglycerol and IP3 in T-cell activation?
  4. What transcription factors are involved in T cell activation?

 

Cytokines

ASSIGNED READING CHAPTER 13: pp 313-334

OUTLINE/SUMMARY

  1. Properties of Cytokines
  2. Cytokine Receptors
  3. Cytokine Antagonists
  4. Cytokine Secretion by T cells
  5. Cytokine Related Diseases
  6. Therapeutic Uses of Cytokines

PERFORMANCE OBJECTIVES

DEFINE THE FOLLOWING KEY TERMS:

autocrine chemokine colony stimulating factors( CSF)
granulocyte CSF cytokines tumour necrosis factor (TNF
monokines lymphokines interleukin IL-1 through IL-15
paracrine Interferons  

 

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

  1. Describe the role of cytokines in the development of immunity
  2. Construct a table of the major interleukins and their functions
  3. Discuss the role of IL-2 in immune regulation
  4. classify the major families of cytokines
  5. Describe the positive and negative regulatory roles of transforming growth factor Beta
  6. Discuss Tumour Necrosis Factors (TNF)

SHORT ANSWER QUESTIONS DIFFERENTIATE the following terms:

  • The difficulty in characterizing IL-1 is caused by the fact that it seems to be made by every cell and seems to be able to affect every cell. Explain.
  • What is Il-1's primary function in immune cell interactions?
  • Distinguish betweeen IL-1alpha and IL-1-beta.
  • Briefly discuss some important immune functions of IL-2. IL-2 is an autocrine Tcell growth factor. Explain.
  • Briefly, discuss the significance of the three forms of the IL-2 receptor.
  • What is the connection between IL-2 production fna IFN-gamma production?
  • Compare and contrast TNF-beta and TNF-alpha.
  • Briefly describe the CSFs.
  • Why do you think IFN-gamma was considered to be a "magic bullet"?
  • Explain how some cancer cells that can make TGF-beta are immunosuppressive.
  • Helper T cells can be divided into two subsets based on their lymphokine secretion profile. Explain.

    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:

    C1q anaphyltoxin inactivator anaphylatoxins
    C1 C1 inhibitor (C1-INH) alternative pathway
    C1r C3 convertase amplification phase
    C1s C3b/C4b receptor(CR1) activation phase
    C2 C4 binding protein (C4-bp) complement
    C2a C5 convertase Factor B
    C2b classical pathway Factor D
    C3 membrane attack phase Factor H
    C3a complement system Factor I
    C3b immune adherence opsonization
    C4 C5b C7
    C4a C4b C6 C8
    C5 C9 CD59
    C5a membrane attack complex(MAC) properdin
    S protein    

    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:

    Inflammation[357] extravasation [358] cell adhesion molecules(CAMs)[358]
    selectin [358] integrin [358] Leukocyte adhesion deficiency (LAD)[359]
    mucin [358 chemoattractants [360] G proteins [361]
    kinins [367] chemokines[361 365] High endothelial venules (HEV) [361]
    fibrin [367] naive lymphocytes[362] cyclooxygenase pathway [368]
    clot [367] effector lymphocytes [363] trafficking or homing of lymphocytes[361]
    plasmin[367] leukotriense [368] lipoxygenase pathway [368]
    complement[367] chemotaxis [369] respiratory burst [369]
    arachidonic acid [368] opsonization [369] Slows reacting substances of anaphylaxis (SRS-A)[368]
    prostaglandins [368] vasodilation [370] acute phase proteins [371]
    fibrosis [373] granuloma [373] multinucleated giant cells [373]
    corticosteroids [376]    

    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

    clonal anergy clonal deletion immunological tolerance
    tolerogen Suppressor T cells  

    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:

    allergen allergy anaphylactic shock
    anaphylaxis anergy contact sensitivity
    basophils atopy delayed type hypersensitivity
    degranulation hypersensitivity homocytotropic antibodies
    desenstization hyposensitivity immediate hypersensitivity
    granulomas late phase reaction mast cells
    sensitization senstizing dose shocking dose
    systemic anaphlyaxis triple response edema
    erythema wheal and flare tubercles
    Type I hypersensitivity tuberculosis tuberculin skin reaction
    Type II hypersensitivity Type II hypersensitivity Type IV hypersensitivity

    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?

    Vaccines

    ASSIGNED READING CHAPTER 18: pp 443-458 OUTLINE/SUMMARY

    1. Active vs Passive Immunization
    2. Vaccines for Active Immunization
    3. Whole Organism Vaccines
    4. Attentuated viral or bactrial vaccines
    5. Inactivated viral or bactrial vaccines
    6. Purified macromolecules as vaccines
      • polysaccharides
      • toxoids
      • Recombinant antigens
    7. Recombinant Vector Vaccines
    8. DNA Vaccines
    9. Synthethetic Peptide Vaccines
    10. Multivalent Subunit Vaccines
    11. Anti-Idiotype Vaccines
    12. Vaccines for Passive Immunization
      • Applications
      • Humanized antibodies

    PERFORMANCE OBJECTIVES

    DEFINE THE FOLLOWING KEY TERMS:

    passive immunization [444] active immunization [445] vaccine[445]
    boosters[445] herd immunity [446] attenuated vaccines [448]
    inactivated vaccines[448] reversion [449] toxoid[451]
    vector [451] vector vaccines [451] antiidiotype vaccine [455]
    Immunostimulating Complexes (ISCOMS) [454    
    solid matric antibody antigens (SMAA) [454    

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

    1. Compare the acquisition passive and active immunization and give specific examples of each [444]
    2. Discuss the recommended program for Childhood immunizations.[445]
    3. Construct a table to compare the advantages and disadvantages of attentuated vs inactivated vaccines.
    4. compare the risks associated with attenturated or inactivated vaccines vs specific purified macromolecular vaccines.
    5. Compare the three general forms of purified macromolecular vaccines; polysaccharide, toxoid, and recombinant antigens
    6. Draw a diagram to show the steps in the production of a vaccina virus vector vaccine[452]
    7. Draw a diagram to show the uses of an anti-idiotypeantibody as a vaccine.
    8. Discuss the advantages of anti-idiotype vaccines[455]
    9. Compare solid matrix antibody-antigen complexes with immunostimulating complexes in the development of multivalent subunit vaccines. [455]

    SHORT ANSWER QUESTIONS

    1. Differentiate between variolation and vaccination.
    2. Define vaccine. Name fouR types of vaccines and give examples of each.

    Infection & Immunity

    CHAPTER 19: Immune Response to Infectious Disease

    THIS CHAPTER WILL NOT BE DEALT WITH IN THIS COURSE AS IT IS THE FOCUS OF THE INFECTIOUS DISEASE COURSE AND THE MEDICAL MICROBIOLOGY COURSE

    Autoimmunity

    ASSIGNED READING

    CHAPTER 20: pp 485-505

    OUTLINE/SUMMARY

    1. Organ Specific Autoimmune Diseases
    2. Direct cellular damage
      • Hashimoto's thyroiditis
      • autoimmune anemias
      • Goodpasture's syndrome
      • insulin dependent diabetes mellitus (IDDM)
    3. Antibody effects
      • Grave's disease
      • myasthenia gravis
    4. Systemic Autoimmune Diseases
      • systemic lupus erythematous (SLE)
      • multiple sclerosis (MS)
      • rheumatoid arthritis (RA)
    5. Animal Models
      • Spontaneous autoimmunity
      • Experimentally induced
    6. TCR & MHC in Autoimmunity
      • CD4+ cells
      • MHC
      • TCR
    7. Induction of Autoimmunity
      • Relase of sequestered antigen
      • molecular mimicry
      • Wrong expression of MHC-II
      • Polyclonal B cell activation
    8. Experimental Treatment
      • T cell vaccination
      • Peptide blockage
      • MABs
      • Tolerance induction

    PERFORMANCE OBJECTIVES

    DEFINE THE FOLLOWING KEY TERMS:

    autoantigens autoimmunity autoimmune hemolytic diseases
    cold antibody Graves disease autoimmune hemolytic anemia
    Warm antibody Hasimoto's thyroiditis thrombocytopenic purpura
    glomerulonephritis myasthenia gravis autoimmune hemolytic anemia
    rheumatic fever Horror Autoxicus Insulin dependent diabetes millitus ( Type I)
    rheumatoid arrthritis allergic encephalomyeltis Organ specific autoimmune diseases
      systemic lupus erythematosis systemic autoimmune diseases

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

    1. Show how the origins of autoimmune disease may lie in the immune process, the self antigens or both.
    2. Describe two major events that may lead to autoimmune disease
    3. Distinguish between cell mediated and antibody mediated autoimmune diseases, give two specific examples of each and discuss these examples.
    4. Discuss the treatment of autoimmune diseases

    SHORT ANSWER QUESTIONS

    1. 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.
    2. The idea of "Horror autotoxicus" was proposed in 1901 to suggest that reactions against self could not occur.
    3. Current evidence suggests otherwise. Explain.
    4. Other than the characteristic of foreigness, self antigens and exogenous antigens are not inherently different. Explain?
    5. What are Witebsky's postulates?
    6. Why are they important in describing autoimmune disease?
    7. The origin of an autoimmune disorder may lie in the immune process, the self antigens, or both. Explain.
    8. What are the two major events that could lead to an autoimmune disease?
    9. List some other possibilities.
    10. The description of SLE includes three mechanistic elemtns; What are they?
    11. In Hashimoto's disease, high levels of antibodies against thyroglobulin are found. Yet these antibodies do not seem to cause the disease. Explain.
    12. Compare and contrast the three lines of treatment for RA.
    13. Briefly discuss some autoimmune disease that can follow bacterial infections.
    14. Why would the induction of tolerance to an autoantigen, which is causing disease, be one of the most effective treatment approaches for autoimmunity?

    Immunodeficiency Diseases ASSIGNED READING Chapter 21: pp 507-521 OUTLINE/SUMMARY

    1. Phagocytic Deficiencies
      • Reduced Neutrophils
      • Defective phagocytes
      • adherence defects
      • chemotactic defectgs
      • killing defects
    2. Humoral Deficiencies
      • X-linked agammaglobulinemia
      • X-linked hyper-IgM Syndrome
      • Common variable hypogammaglobulinemia
      • Selective immunoglobulin deficiences
    3. Cell mediated Deficiences
      • DiGeorge sysndrome
      • Nude mice
    4. Combined Immunodeficiences
      • Reticular dysgenesis
      • Bare lymphocyte syndrome
      • SCID
      • Wiskott-Aldrich Syndrome
    5. Complement Deficiences

    PERFORMANCE OBJECTIVES

    DEFINE THE FOLLOWING KEY TERMS:

    immunodeficiency [507] Wiskott-Aldrich syndrome (WAS)[519]
    neutropenia[508] congenital agranulocytosis [508]
    granulocytopenia[508] leukocyte-adhesion deficiency [508]
    agranulocytosis[508] lazy leukocyte syndrome [510]
    selective Iga Deficiency [ 514] chronic granulomatous disease (CGD)[510],
    nude mice [515] X linked agammaglobulinemia [511],
    reticular dysgenesis [516 X-linked hyper IgM (XHM) syndrome [512]
    bare lymphocyte syndrome [516] common variable hypogammaglobulinemia(CVH) [513
    X linked SCID [518] DiGeorge Syndrome (Congential thymic aplasia) [515]
      severe combined immunodeficiency disease (SCID)[517]

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

    1. construct a table comparing four different
    2. phagocytic deficiency diseases [510]
    3. Construct a table comparing 4 different humoral deficiences;
      • X linked agammaglobulinemia [511],
      • X-linked hyper IgM (XHM) syndrome [512],
      • common variable hypogammaglobulinemia(CVH) [513],
      • selective Iga Deficiency [514]
    4. Draw a diagram of hematopoiesis and indicate congential defects that impair the immune response for
      • phagocytic deficiences,
      • humoral deficiences
      • cell mediated deficiciences
      • combined immunodeficiencies
    5. Discuss the impact of T cell deficiencies
    6. Construct a table of the combined immunodeficiences that shows the disease, the immune system deficiency and the possible mechanism [517]
    7. Discuss the use of CB-17 SCID mice as a model system

    SHORT ANSWER QUESTIONS

    1. How does immunodificiency differ from immunotolerance?

    AIDS

    ASSIGNED READING Chapter 22: pp 523-554 OUTLINE/SUMMARY

    1. Discovery
    2. Human Immunodeficiency Virus (HIV)
      • Retroviruses
      • Structure of HIV
      • HIV Infection of Targety Cells
      • Transmission of HIV
      • HIV Genome
      • Activation of HIV Provirus
      • Expression of HIV proviral DNA
      • Genetic variation
    3. Diagnosis of HIV
      • Serology
      • Screening tests
    4. Diagnosis of AIDS
    5. Destruction of CD4+ T cells
    6. CD4+ T cells infected with HIV
    7. Destruction of CD4+ T cells uninfected with HIV
      • Anti GP120
      • GP120
      • Syncytia
      • Maturation inhibition
    8. Immunologic Abnormalities in Aids
      • Lymph node pathology
      • Reduced response to antigen
      • Ineffective antibody
      • Cytokine imbalance
      • Decreased DTH response
      • Impaired CTL activity
    9. Development of AIDS Vaccine
      • Obstacles
      • glycoproteins
      • Attenutated viruses
      • Recombinant viruses
      • Synthetic peptides

    PERFORMANCE OBJECTIVES

    DEFINE THE FOLLOWING KEY TERMS:

    long terminal repeats[531 Acquired immunodificiency syndrome(AIDS) [524] fusin[529]
    HIV-1 Human immunodeficiency virus (HIV)[524] integrase[530]
    HIV-2 simian immunodificiency virus (SIV) [526] budding[530]
    HIV-0 cytopathic retroviruses[524] syncytium[]542]
    retroviruses [524] transforming retroviruses [524] Karposi's sacrcoma
    V3 loop[536] reverse transcriptase [526] fusogenic domain[528]
    seroconversion[536] opportunistic infections [524] crown region[536]

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

    1. Draw and label cross sectional diagram of an HIV virion
    2. Draw and label a diagram of the genome of HIV-1
    3. Discuss the factors that contribute to the genetic variation of HIV
    4. Construct a table of the cell types that can be infected by HIV[530].
    5. Draw and label a diagram show the steps in the infection of a target cell by HIV[528]
    6. Draw and label a diagram that shows activation of HIV provirus [528]
    7. Discuss the origins of HIV-1, HIV-2 and HIV-0.
    8. Draw a diagram to show the early and late stages in the expression of HIV-1 proviral DNA [534]
    9. Label a diagram of HIV-1 envelope glycoproteins.
    10. Describe the screening tests for HIV infection [537].
    11. Describe the clinical symptoms of AIDS[537]
    12. Describe the various mechanisms for the depletion of CD4+ cells in AIDS patients[538-543]
    13. Construct a Table summarizing the immunologic abnormalities associated with HIV infection.
    14. Construct a table showing the estimated incidence of AIDS around the world[525]

    SHORT ANSWER QUESTIONS

    Transplantation Immunology ASSIGNED READING CHAPTER 23: pp 555-572 OUTLINE/SUMMARY

    1. Immunological Basis of Graft Rejection
      • Specificity & memory
      • Cell mediated responses
      • Transplantation antigens
      • Mechanisms of graft rejection
      • Sensitization stage
      • Effector stage
    2. Clinical Manifestions of Graft Rejection
      • Hyperacute rejection
      • Acute Rejection
      • Chronic rejection
    3. Tissue Typing
    4. General Immunosupressive Therapy
      • Mitotic inhibitors
      • Corticosteroids
      • Cyclosporin A
      • Total irradiation
    5. Specific Immunosupressive Therapy
      • MABs to T cells
      • Block co-stimulatory signal
      • Microchimeras
    6. Clinical Transplantation
      • Bone marrow transplants
      • Organ transplants
      • Xenotranplants
      • Immunologically priveleged sites

    PERFORMANCE OBJECTIVES

    DEFINE THE FOLLOWING KEY TERMS:

    allogtraft alloreactivity autograft
    chronic rejection Class I MHC Class II MHC
    first set rejection graft grafting
    Graft vs host reaction privileged sites privileged tissues
    mixed lymphocyte reaction syngraft transplant
    second set rejection transplantation xenograft
    transplantation immunity    

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

    1. Show that the cell mediated response to transplants in the same as the immune response to any other foreign antigen
    2. Describe four types of grafts
    3. Describe the five transplantation laws
    4. Distinguish among first set rejection, second set rejection and chronic rejection;
    5. Differentiate between host versus graft reaction and graft versus host reaction.
    6. Compare the contribution of Class I and Class II MHC to graft rejection.
    7. Comment on which T cells are responsible for graft rejection
    8. Describe serologic tissue typing.
    9. Describe the mixed lymphocyte reactions and why you would want to use the MLR in tissue typing
    10. Rank the success rate for transplants of different tissues and organs

    SHORT ANSWER QUESTIONS

    1. What do we mean when we say that the immune system is the greatest obstacle to most transplants?
    2. What is the difference between autograft and syngraft? Give examples of both.
    3. How do we know that the immune system is involved in allograft rejection?
    4. Are antibodies or T cells the main mediators of rejection?
    5. ompare and contrast first set rejection and second set rejection.
    6. What does second set rejection suggest about the similiarity of transplantation antigens?
    7. What conditions could lead to a graft vs host response (GvHR)?
    8. Even though class II antigens are found mainly on immune cells, they can still contribute to graft rejection. How?
    9. What may be the biologic significance of alloreactivity?
    10. Describe serologic tissue typeing.
    11. Describe the MLR. Why is this test done in addition to serologic tissue typing?
    12. Differentiate between privileged sites and privileged tissues.

    Cancer & Immunity ASSIGNED READING Chapter 24: pp 573-596 OUTLINE/SUMMARY

    1. Origins & Terms
    2. Malignant Transformation
    3. Oncogenes
      • Induction of cell proliferation
      • Inhibition of cell proliferation
      • Regulation of apotosis
    4. Tumours of the Immune System
    5. Tumour Antigens
      • Tumour specific Antigens
      • chemically induced
      • virally induced
    6. Tumour associated antigens
      • oncofetal tumour antigens
      • oncogene proteins
      • TATAs on human melanomas
    7. Immune Response to Tumours
      • NK cells & macrophages
      • Immune surveillance theory
    8. Tumour Evasion of Immune Response
      • Immunologic enhancement
      • Modulation of tumour antigens
      • Reduce MHC-I
      • No co-stimulatory signal
    9. Cancer Immunotherapy
      • Modify Co-stimulatory signal
      • Enhance APC activity
      • Cytokine therapy
      • MABs
      • Tumour cell vaccines

    PERFORMANCE OBJECTIVES

    DEFINE THE FOLLOWING KEY TERMS:

    Antibody dependent cell mediated cytotoxicity (ADCC) benign tumour carcinogens
    tumour specific transplantation antigens natural killer cells (NK) immunotoxins
    immalignancymune surveillance Specific immunotherapy neoplasm
    non specific immunotherapy tumour specific antigens oncogens
    Lymphokine activated killer cell(LAK) malignant tumour tumour
    tmour associated transplantation antigens oncofetal antigens cancer
    tumour associated antigens proto oncogens metastasis

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

    1. Differentiate between a benign tumour and a malignant tumour.
    2. Describe the concept of immunosurveillance
    3. Describe the different ways that tumours can camouflage themselves to evade immune defenses,
    4. Discuss the advantages of immunotherapy over other forms of cancer therapy.
    5. Distinguish between specific and nonspecific immunotheraphy with the use of specific examples.
    6. Describe immunotoxins.
    7. Describe the development of humanized antibodies to tumour antigens
    8. Evalulate the contribution of T cells, NK cells, Macrophages, and B cells to tumour immunity.
    9. Distinguish between tumour specific transplantation antigens and tumour assoicated transplantation antigens.
    10. Describe oncofetal antigens.

    SHORT ANSWER QUESTIONS

    1. Explain how some cancer cells that can make TGF-beta are immunosuppressive.
    2. Tumours and transplants are similar to one another,yet very different. Explain this observation in the context of what the immune system recognizes and the result of this recognition.
    3. The qualities of proliferation and differentiation are essentially all that distinguishes a normal cell from a cancer cell. Explain.
    4. Design an experiment using mice that proves that the immune system provides immunity against tumours.
    5. Distinguish between tumour-specific transplantation antigens (TSTA) and tumour associated transplantation antigens (TATA).
    6. Design an experiment to show Tumour associated Transplantation Antigens (TATA).
    7. What is the main difference separating cell surface antigens from chemically induced and virually induced cancers? Speculate on why this difference leads to difficulty in designing anticancer vaccines.
    8. What are oncofetal antigens? Are they important in tumour immunity? Why?
    9. What is immune surveillance? All evidence for immune surveillance is indirect. Speculate on how you could get direct evidence.
    10. What immune cells play a role in tumour rejection? Briefly describe how each accomplishes this task. Include such things as cytokines, perforins, ADCC etc.
    11. Cancers camouflage themselves to evade antitumour defenses. Pick three possible forms of camouflage that you think are most important, describe them and state why you think they are most important.
    12. What are immunotoxins?
    13. Surgery, radiation and chemotherapy are the methods most widely used to treat cancer patients. What are the problems with this regimen, and how could immunotherapy overcome these problems. Distinguish between specific and nonspecific immunotherapy.