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Preface
Immunology is a relatively recent discipline area in the life / biological sciences. It is an
integration of many sub-disciplines of biology, most notably: microbiology, parasitology,
histology, molecular and cell biology, physiology genetics and biochemistry. The course here is a
series of lectures providing comprehensive introduction to basic defense mechanisms that protect
individuals against infections and cancers.
In Immunology the student will become acquainted with theories and phenomena explaining
the interactions of animals and human beings with their environments, and with other living
organisms. Studies in immunology are leading to advances in clinical medicine, including
understanding allergies, transplant rejection, autoimmune diseases, such as rheumatoid arthritis
and insulin-dependent diabetes, and the development of new vaccines. The course should also
provide ample insights into areas of basic research as well as topics related to modern human
immunology. Students are expected to analyze disease processes in the light of current
immunological thinkinG
Course Objectives:
To develop an awareness of experimental design and scientific methods
To acquire a working vocabulary in immunology.
To understand and discuss the development and evolution of the immune system.
To gain an understanding of the key cells involved in the immune responsE
To understand the relationship of antigen, antibody, and antigen receptor molecules.
To gain a basic knowledge of the generation of diversity involved in antibodies and T-cell
antigen receptors.
To distinguish and understand the humoral and cell-mediated immune responses.
To gain a basic understanding of the current theories on the regulation of the immune
responsE
To discuss the host's ability to mount an immune response to invading microorganisms
Tentative Lecture Syllabus of Immunology
Chapter 1 Introduction To Immunology
Chapter 2 Overview Of The Immune System
Chapter 3 Antigens
Chapter 4 Ig Structure and Function
Chapter 5 Organization and diversity of Ig Genes
Chapter 6 Antigen Antibody Interaction
Chapter 7 Complement System
Chapter 8 Cytokines
Chapter 9 CD And Adhesion Molecules
Chapter 10 MHC
Chapter 11 Innate Immunity And Innate Immune Cells
Chapter 12 APCs, Antigen Processing And Presentation
Chapter 13 Development Of Immune Cells
Chapter 14 T Cell Mediated Adaptive Immunity
Chapter 15 B Cell Mediated Humoral Immunity
Chapter 16 Immune Regulation
Chapter 17 Immune Tolerance
Chapter 18 Hypersensitivity
Teaching outline
Chapter 3 Antigens
A Antigen
1 Antigen
2 Haptens
3 Properties Of Antigen
4 Immunogen Vs. Antigen
B Factor That Influence Immunogenicity
1 Foreigness
a Determined During Embryonic Development
b Foreigness Increases With Phylogenetic Distance
2 Complexity
a Heterogeneity
b Size And Heterogeneity
3 Molecular Size
4 Charge
a Polar Sites Better Than Non-Polar
b What Types Of Bonds Are Necessary For Ag/Ab Binding?
5 Degradability
a Lysosomal Enzymes Must Recognise Ag
b LG Insoluble Molecules Better Than Sm., Soluble Ones
c Proteins With D-Amino Acids Not Immunogenic
C Immunogenicity Of Macromolecules
1 Proteins
2 Carbohydrates
3 Nucleic Acids
4 Lipids
D B-Cell Epitopes
1 Size And Shape Determined By Paratope
2 Epitopes H'philic And Accessible
3 Due To Sequential Or Non-Sequential AA On Protein Surface
4 Immunodominant Epitopes
E T-Cell Epitopes
1 Oligomeric Peptides
a MHC Binding Site Determines Size
b Best Sizes For MHC I And MHC II?
2 Trimolecular Interactions
a Agretope Binds MHC
b Epitope Binds TCR
3 Sequential Amino Acids
a Processed Inside Phagocytic Cell
b No Tertiary Structure Remains
4 Amphipathtic Peptides
a Used To Predict Immunodom.
b 18 Of 23 Immunodominant Peptides Were Amphipathic
5 MHC Determines Immunodominant Peptides:
a L-Cell (Fibroblast Experiment)
b MHC II Genes Transfected Into L-Cells
c Look For Activation Of T-Cells
6 SuperatIgEns
a Potent T-Cell Mitogens
b Cross-Link TCR And MHC Without Specificity
c How Can They Make Us Ill?
Chapter 7 Complement
A Introduction
1 Complement System
2 Proteins Of Complement System
a Innate Component
b Regulatory Protein
c Complement Receptors
B Pathways Of Complement Activation
1 Classical Pathway
a Activators
b Cascade Activation
c Significance
2 Alternative Pathway
a Activators
b Cascade Activation
c Significance
3 Lectin Pathway
a Activators
b Cascade Activation
c Significance
4 Common Lytic Pathway
a Formation O F C5b67 Complex
b Formation Of Membrane Attack Complex(MAC)
C Biologically Active Products Of Complement Activation
1 Kinin Production
2 Anaphylotoxins
a C3a
b C4a
c C5a
3 Chemotactic Factors
a C5a
b C5b67
4 Opsinins
a C3b
b C4b
5 Other Biologically Active Products Of C Activation
a Degradation Product Of C3: C3d, C3e, C3b
D Biological Consequences Of Complement Activaton
1 Cell Ysis
a Broad Spectrum Of Target Lysis
b Major Of MAC
2 Mediate Inflammatory Response
— C3a, C4a, And C5a
3 Opsonization Of Antigen
— C3b And C4b
4 Viral Neutralization
5 Clearance Of Immune Complexes
Chapter 8 Cytokines
A Introduction
1 Cytokine
2 Major functions
B Properties Of Cytokines
1 General features Of Cytokines
2 Actions Of Cytokines: In Three Manners
a Autocrine
b Paracrine
c Endocrines
3 Cytokine Atributiions
a Pleiotropy
b Redundancy
c Synergy
d Antagonism
4 Classications Of Cytokines
a Lymphokines
b Monokines
c Interleukins(IL)
d Chemokines
5 Distinction Between Cytokines, Hormones And Growth Factors
C Cytokine Families: Cytokines Belong To Four Structural Families
1 The Hematopoietin Family
a Members
— IL-2 , 4
2 The Interferon Family
a Members
— IFNα, β, γ
3 The Chemokine Family
a Members
— IL-8, MIP-1
4 The Tumor Necrosis Factor Family
a Members
— TNFα, β
D Cytokine Receptors
1 Cytokine Receptor Families
a Immunoglobulin Superfamily Receptors
— IL-1, M-CSF, C-Kit
b Class I Cytokine Receptor Family (Also Hematopoietin Receptor Family)
— IL-2, 4, 7, 9, 12, 15, prolactin, et al.
c Class II Cytokine Receptor Family (Also Interferon Receptor Family)
— IFNα, β, γ, IL-10
d TNF Receptor Family
— TNFα, β, CD40, NGF
e Chemokine Receptor Family
— IL-8, MIP-1, MCAF, RANTES, et al.
2 Subfamilies Of Class I Cytokine Family: Signaling Units In Common
a GM-CSF Receptor Subfamily (Common β Subunit)
— GM-CSF, IL-3, 5
b IL-6 Receptor Subfamily (Common gp130 Subunit)
— IL-6, 11, CNTF, LIF/OSM
c IL-2 Receptor Subfamily (Common γ Subunit)
— IL-2, 4, 7, 9, 15
3 IL-2 receptor(IL-2R)
a Composition Of IL-2R
— α, β, γ Chains
b Forms Of IL-2R
— Low Affinity IL-2R
— Intermediate Affinity IL-2R
— High Affinity IL-2R
c Comparison Of Chains Of IL-2R Chains And Receptor
4 Cytokine Receptor Activated Signaling Pathways
a Overview of Signaling Pathway By IFNγ
b JAK-STAT Signaling
— STAT-JAK Interaction With Selected Cytokine Receptors
E Cytokine Atangonists
1 Cytokine Atangonists
2 Action of Cytokine Atangonists
a direct binding to cytokine receptors
— Receptor Atangonists: IL-1Ra
b direct binding to cytokines
— Soluble Cytokine Receptors: Soluble IFNγ Receptor
3 Biological Significance Of Cytokine Atangonists
F Cytokine Secretion by Th1 And Th2 Subsets
1 Development of Th1 And Th2 Cells
2 Cytokine secretion by Th1 Subset
a IFNγ, IL-2, TNFα
3 Cytokine secretion by Th2 Subset
a IL-4, 5, 6 10, 13
4 Cross-Regulation between Th1 And Th2 cells: Cytokine Enviroment Determines
a Shift Toward Th1
b Shift Toward Th2
5 Th1/Th2 Balance Determins Disease Outcomes
G Cytokine Related Diseases
1 Bacterial Septic Shock
a Endotoxin And IL-1, TNFα
2 Bacterial Toxic Shock by Superantigen
a Toxins And IL-1, TNFα
3 Lymphoid And Myeloid Cancer
a IL-6 And Cardiac Myxoma, Myeloma
4 Chaga`s Disease Caused By Parasite
H Therapeutic Application Of Cytokines And Cytokine Receptors
1 Application Of Cytokines
a IFNα, IL-2
2 Application Of Cytokine Receptors
a Anti-TAC: Anti high Affinity IL-2R
3 Example Of Clinical Use
I Cytokine In Haematopoiesis
Chapter 18 Hypersensitivity
I Introduction
A Hypersensitivity
Undesirable (Damaging, Discomfort-Producing And Sometimes Fatal) Reactions
B Major Types
a Type I - IgE-Mediated Hypersensitivity
b Type II - Antibody-Mediated Cytotoxic Hypersensitivity
c Type III - IC Mediated Hypersensitivity
d Type IV - Delayed-Type Hypersensitivity
II Type I (Immediate Hypersensitivity)
a IgE Mediated
b Symptoms 2 - 30 Minutes
A Sensitization Phase
1 Allergen Activates T helper
a Release Of Il-4
2 Allergen And Il-4 Bind B-Cell
a Plasma Cells Make IgE
3 IgE Binds Mast Cell Or Basophil
4 Passive Transfer Of Sensitization Possible
5 FcεRI (Member Of Ig Superfamily)
a IgE Receptor
b Alpha Chain Interacts With CH3 - CH3 And CH4 - CH4 Of IgE
c Beta Chain
d Two Gamma
B Activation Phase
1 Cross-Linking Of FcεRI By Allergen
a Aggregation Of Receptors
b Activation Of TPKs Due To Transauto Phosphorylation
c Methylation Of Phospholipids In Plasma Membrane
d Calcium Increases Lead To
e Activation Of Adenylate Cyclase
f Subsequent Decrease In Camp Required For Degranulation
2 Affinity Of IgE For Allergen Important
a If Low Affinity, Aggregate Will Not Persist Long Enough
b High Affinity Means Aggregate Forms Long Enough To Complete Cascade
C Effector Phase
1 Histamine Release (Primary Mediator)
a Increased Vascular Permeability
b Contraction Of Smooth Muscles
c Nasal And Lacrimal Secretions
d Release Of Mucus From Goblet Cells
2 Anti-Histamines
a Compete With Histamine For Histamine Receptors
b Ethylamine Group
3 Leukotrienes And Prostaglandins
a Secondary Mediators
b Cause:
c Effects Longer Lasting
D Allergic Reactions
1 Allergic Rhinitis
a Hay Fever
b Upper Respiratory Problems
c Genetic
2 Asthma
a Contraction Of Smooth Muscle In Airways
b Mast Cells In Lower Respiratory Tract Degranulate
c Leukotrienes May Bear Greatest Responsibility
d Why Seeing An Increase?
3 Systemic Anaphylaxis (Anaphylactic Shock)
a Explosive Release Of Many Mast Cells
b Symptoms:
c Intervention With Epinephrine
4 Food Allergies
a Gi Distress
b Atopic Urticaria
E Diagnosis/Treatment Of Allergies
1 Skin Sensitivity Testing
a Scratching Or Intradermal Injection Of Allergen
b Look For Wheal (Swelling Due To Serum) And Flare
2 Hyposensitization
a Gradually Increase Dose Of Allergen
b Possibly Effective Due To:
F Reasons For Allergic Susceptibility
1 MHC Presents Allergen
2 TCR Recognize MHC/Allergen
3 Differential Response Of T Cells To Allergen
4 Defect In IgE Suppression
5 Increased Permeability Of Respiratory And G I Tracts To Allergen
6 Increased Sensitivity To Histamine
7 Increased IgE Receptors On Mast Cells
III Type II (Ab-Mediated Cytotoxic)
1 Mechanism:
a IgG And IgM Binding To Fixed Target Ags
b Lysis Of Cell
2 .Typical Disease
a Erythroblastosis Fetalis
b Transfusion Rxns
IV Type III (Immune Complex)
1 Mechanism
a Involve Reactions Against Soluble Antigens Circulating In Serum.
b Ab-Ag Immune complex Are Deposited In Organs,
2 Typical Disease
a Serum Sickness (Generalized)
b Localized = Arthus Rxn.
c Autoimmune
V Type IV= Delayed Hypersensitivity
1 Mechanism
a Cell Mediated Immunity
b Sensitization Of Subpopulation Of Th
c Influx And Activation Of Macrophages
— Release Of Lytic Enzymes
— Erythema And Induration
d Variety Of Cytokines Released
2 Examples:
a Tuberculosis
b Graft Rejection
c Contact Dermatitis
— Poison Oak
— Pentadecacatechol (Hydrophob )
— Phagocytosis By Langerhans Cells
— Presentation By MHC II To TDTH
— Phago. By Langerhans Cells
— Presentation By MHC II To Tdth
References:
1 Fundamental Immunology 5th edition (2003): by William E., Md Pau.
2 Immunology 5th edition(2002): by Goldspy AA, Kindt TJ, Osborne BA, Kuby J.
3 Essentials of Clinical Immunology(1999): by Chapel, Helen.; Haeney, Mansel.; Misbah, Siraj.; Snowden,
Neil.
4 Innate immunity: R. Alan B. Ezekowitz MB ChB, DPhil, FAAP.
5 Immunolgy 6th edtion(2001), by Ivan Roiit, Jonathan Brostoff, David Male.
6 Cellular and Molecular Immunolgy 4th (2000): by Abul K Abbas, Andrew H, Lichman Jordan S. Pober.
7 Medical Immunology 10th (2002): by Tristram GP, Daniel PS, Abba IT, John BI.