BI385 – Immunology
Semester II 2008-2009
Professor Elizabeth Godrick
Boston University Biology Department
Contact Information
SCI301: (617) 353-2472, Godrick@bu.edu
OH: Tr 12noon -1:30pm,; F 8:30am-10:am
Text
Immunobiology 7th ed. Murphy ISBN: 081534123-7
(Available at BU Bookstore)
Course Website
http://webct.bu.edu______________________________
BI 385 Immunology: Prereq: BI 203, Recommended: BI 206, BI 315. The constituents and regulation of mammalian
immune systems are described at the levels of the gene, protein, and cell. Topics include innate immunity; T cell, B
cell, and MHC genetics, development, recognition and responses; signaling pathways; tolerance; memory;
hypersensitivities; autoimmunity; transplantation; evolution and manipulation of defense systems. Three hours lecture,
one hour discussion.
Date
January 15
January 20
January 22
Lecture Topics
Introduction: The Self vs the Nonself
Innate Immunity
Anatomical/Physiological Barriers
Players in Innate & Adaptive Immunity
Cells, Tissues, and Organs
Pattern Recognition
Complement (C’) System
Safeguards for Host from C’ Damage
Chemical Mediators-Cytokines
Chemokines; Tumor Necrosis Factor-,
Interferons
Inflammatory Response
Cell Adhesion Molecules
Leukocyte Migration
Adaptive Immunity: The Large Picture
Response to a Viral Antigen
Response to a Bacterium/Toxin/Toxoid
Exam
January 27
Text Chapters
1
1,2
pp.53-59
pp.61-82
pp. 92-94
pp. 83-86
pp. 90-92
pp. 10-12; 40-53
pp. 87-90
1
January 29
Clonal Selection
Immunogens; Antigens; Superantigens
pp. 14-15
pp. 735-739;120-122
pp.206-207
3: 126-139
February 3
Major Histocompatibility Complexes (MHCs)
Antigen Processing for and Presentation in
MHC class I
MHC class II
MHC Functions and Genetics
February 5
Antigen Recognition by T, NKT,
and Treg Cell Receptors
Antigen Recognition by B Cell Receptors
Immunoglobulin Structure: Light & Heavy
Chains; Variable/Constant Ends
3: 123-138
pp. 354-356
3:111-123
pp. 162-164
February 10
February 12
February 17
February 19
February 24
February 26
Genetics of Lymphocyte Antigen Receptors:
B cell Receptors (Immunoglobulins)
Somatic Recombination: V,D &J gene segments
Generation of Diversity: Combinatorial,
Junctional, H & L Chain Combination, Somatic
Hypermutation, Isotype Switching,
T Cell Receptors
Continue Genetics
Begin Signal Transduction in T Cells and B Cells
Antigen Receptor Structures; ITAM Motifs
5
4
4
6
No class due to Monday schedule
Activation of Transcription Factors
Signal Inhibition
Other Signal Receptors/Systems: Toll-like pathways,
Chemokines, Cytokines
Mechanisms of Apoptosis
6
Exam 2
B Cell Development
Pro, Pre, Premature, Naïve Stages
Gene Rearrangements H and L chains, Allelic
Exclusion; Cell Surface Proteins; Tolerance to Self:
Clonal Deletion, Anergy; Receptor Editing,
Ignorance
7
March 3
March 5
T Cell Development:
Double Negatives, Double Positives,
Single Positives, Naïve
CD4 and CD8 T cell
T Cell Gene rearrangements, Cell Surface Proteins
Differences between T & B Cell Development
Tolerance to Self
T Cell Tumors Reflect Developmental Stages
B/T Cell Survival in Peripheral Lymphoid Tissues
7
Dr. Caroline Genco, BUMC
Role of the Innate Immune System in PathogenInduced Chronic Inflammation
Spring Break
March 7-15
March 17
The Mechanism of HIV Infection
Professor Thomas Gilmore
pp. 527-545
Exam 3
March 19
March 24
March 26
March 31
T Cell Mediated Effector Responses
Production of Armed Effector T Cells
Properties of Armed Effector T Cells
T Cell-Mediated Cytotoxicity
Macrophage Activation by TH1 Cells
Humoral Immune Response
B Cell Activation by Armed TH Cells
Activated B cell Metabolism: Phases I & II
Reactions to Thymus Independent Antigens
Immunoglobulin Isotypes Distribution
Immunoglobulin Functions: Toxin Neutralization,
Viral/Bacterial Inhibition, Complement Fixation,
Fc Receptor Function
Course of Immune Rx to Infection ???
8
9
9
pp.421-442
April 2
Immunological Memory
The Mucosal Immune System
April 7
Immune Manipulation vs Pathogens: Vaccines
Factors to Consider: Safety (attenuation, acellular),
Immunogenicity (adjuvants, conjugates), Memory, Rte
of Immunogen
Immune Manipulation vs.Tumors
April 9
April 14
April 16
April 21
Exam IV
Host Defenses in Time & Space: Infectious Agents
and How They Cause Disease
Pathogens Elude Host Defenses
Immunodeficiency Diseases
pp. 442-455
11
15: 687-702
15:672-687
12: 497-507
12: 507-527
Immune System Pathology
Hypersensitivities: Effector Cells & Molecules
Type I (Anaphylactic) IgE Production;
Types II & III; Type IV (Delayed) T cell Response
Immune System Pathology: Autoimmunity
Genetic Factors & Environmental/ Disease Causes
T & B Cell Contributions to Autoimmunity
Control of Autoimmunity
13
14:599-637
15:664-672
Monday Schedule
April 23
April 28
Responses to Alloantigens: Direct, Indirect,
Hyperacute, Chronic, GVH Reactions; Fetal Tolerance
Manipulation to prevent Rejection
April 30
Evolution of the Immune System
_________________ ____________________________________________
14:637-649
15: 655-664
16
May 5?
Grading
Exams (5)
Discussion
90% (Exam 1: 16%, Exam 2: 18%, Exam 3: 18%, Exam 4: 19%, Exam V: 19%)
10%
100%
CAS Academic Code: The CAS Academic Conduct Code is strictly followed. Academic misconduct involves not only direct cheating on
tests, but some more subtle acts as well. All work handed in for credit must be your own, with the exception that you may refer to other
sources if you cite the references using the guide below. It is not permissible to use another student’s work. You may discuss items with
other students but your written work must be your own. If you have any questions you should consult Professor Godrick or the Teaching
fellow before the deadline. We are required to report cases of suspected academic misconduct to the Dean’s Office. Penalties for
violations of the Academic conduct code may include suspension or expulsion from the University.
Examples of References:
Hartwell, et al 2000. Genetics from Genes to Genomes. Chap. 24. McGraw Hill, NY
Hall, Stephen, 1997. A Commotion in the Blood, Life and Death of the Immune System. Henry Holt & Co. NY. 544 pp.
Shedlock DJ and Shen H Apr 11, 2003. Requirement for CD4 T cell help in generating functional CD8 T cell memory Sci 00:337- 339
Zinkernagel RM and Hengartner H. Jul 13, 2001 Regulation of the immune response by antigen Sci 293: 251-253
Special Section Jul 9,2004 Immunotherapy Sci:193-216
Special Section: Jul 13, 2001 Vaccines and Immunity Sci 293:228-236
Discussion Sections
The objective of the session is to look at current immunological techniques.
Students will select a protocol(s) upon which to report to the group examining a paper published within the
last three years which uses a selected immunological technique. Students can choose from but are not limited
to the repertoire of immunological techniques listed below.
Discussion will center about (1) problems with the technique - accuracy, false negatives/positives etc, (2)
alternative protocols experimenters might have considered, and (3) future work. It is estimated three students
will present per session depending on size of discussion section(s).
Administration:
Each student will give instructor 1st, 2nd, and 3rd choices for topic and then be assigned for presentation
throughout semester. The sessions will be organized so each meeting discusses a different protocol. Prior to
talk, students will submit 1-2 page abstract of their talk for class distribution. Difficulty of protocol will be
taken into consideration of presentation/abstract.
Grading:
Abstract
Presentation
Attendance/Participation
Discussion Section
=
=
=
=
%
%
%
10% of total grade.
You are expected to be punctual. Attendance is not taken after the first five minutes.
Possible Protocols (but not limited to) to Discuss
General
Adjuvant use
Enzyme-Linked Immunosorbent assay (ELISA); Capture/Sandwich ELISA
ELISPOT assays for T cells
Radioimmunoassay (RIA)
Competitive Inhibition Assay
Affinity Chromatography
Hemagglutination and Precipitin Reactions
Equilibrium Dialysis (Measurement of Antibody Affinity and Avidity)
Coombs Tests and Detection of Rhesus Incompatibility
Assays/Staining Techniques for Cytokines & Cytokine-Secreting Cells
Monoclonal Antibodies
Phage Display Libraries for Antibody V-region Production
Immunofluorescence Microscopy & Immunoelectron Microscopy
Immunohistochemistry
Immunoprecipitation and co-Immunoprecipitation
Western Blotting/Immunoblotting
Reverse Genetics Applications in gene product isolation/identification
Production of Antibodies by Genetic Engineering
Cellular Applications
Lymphocyte Isolation Procedures from Tissues/Blood
Flow cytometery- using fluorescence-activated cell sorter
Generation of B or T Cell Clones
Generation of B Cell or T Cell Hybrids from Hybridomas
Intracellular Cytokine Staining/Cytokine Capture
Spectratyping -Assay of Diversity of T-Cell Response
Biosensor Assays to Measure Disassociation of Antigen Receptors & Antigen
TUNEL Assay
Assay for Different Cell Types: CD8 T Cells; CD4 T Cells
Microarrays for Gene Expression in Different Lymphocytes
Manipulation of Immune System
Assessment/Transfer of Protective Immunity
Hematopoietic Stem-Cell Transfers
In vivo Depletion of T or B cells
Small RNAs (RNAi or μ RNAs)
Transgenic Mice
Knockout Genes in Lymphoid Cells
Limiting Dilution Cultures
T-Cell Receptor Identification
Possible Journal Sources:
Adv Immunol
Annu. Rev. Immunol
Bioassays
J. Clin.Invest.
Curr. Opinions in Immunol
Cur. Top. Microbiol. Immunol.
Eur.J. Immunol
Hum. Immunol.
J.Immunol
Immunobiology
J. Immuno. Meth
Immunopharmacology
Immunol. Rev.
Immunol. Today
Immunotech.
Inflammat
Infect. Immun.
J. Infect. Dis.
Nature
New Engl. J. Med.
Proc. Nat Acad. Sci
Science
Sem. Immunol.
Trends in Microbiol
Guidelines for BI385 Technique Talks
Please prepare your talks in the manner of a NOVA presentation i.e. for an intelligent, interested audience
but an audience with NO background in the techniques you will describe or to which you will refer.
Please use bulleted high points for what you want the audience to see. Font 20 allows your audience to read
your image. Copy onto transparency or prepare for power point.
Use diagrams to substitute for words whenever you can.
Remember to let me know a week ahead if you will be using power point. You will have to supply your own
laptop. Plan on arriving in the room 5 mins early to make sure you can set up the laptop/projector.
General Steps in your Talk
1- Big Picture
It helps if you start with the big overview of what you will discuss. If you are
presenting two different unrelated experiments—outline up front the common
thread for your audience.
2- Procedures
What were the investigators attempting to do by using the protocol you are
describing? What question(s) were they attempting to ask?
Focus: What do we Know? How do we Know It?
Flow Chart(s) may help here.
Describe procedures
Use Diagrams/cartoons whenever you can to illustrate your talk.
What works/ what doesn’t
3- It helps the audience to understand the procedures if you give some idea of time
involved to run them. Are you discussing a process that takes a day/week/month to
run or something that is completed within minutes/hour? If both—explain.
4- Talk should end with unanswered questions—where does the researcher go from here.
BI385 Presentation
(hand in this form to instructor at beginning of presentation)
Name__________________________
Date___________________________
Title______________________________
1. Knowledge of Topic
1.00
.75
.50
.25
0
2. Organization of Talk
1.00
.75
.50
.25
0
3. Oral Presentation Skills
1.00
.75
.50
.25
0
4. Quality- Power Pt/Transparencies 1.00
.75
.50
.25
0
5. Ability to Answer Questions
.75
.50
.25
0
1.00
Total _______________ /5 possible points
Ranking Scale: Excellent
Comments:
5
Very Good
4
Good
3
Needs considerable work
1
Unacceptable/Missing
0
Discussion Section Talks
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