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OVERVIEW of THE IMMUNE SYSTEM
Diseases
Immunocompetence/Immunodeficiency
Infectious Disease
InflammationAllergy
Organ-Specific Immunologic Disorders
Connective Tissue Disorders
Immunohematology
Transplantation Immunology
Cancer/Therapy
Reproductive Immunology
Neuro Immunology
Historical Immunology
Infectious Disease
Serology
Immunochemistry
Cellular Immunology
Immunological Heroes – Nobel Prize WinnersMetchnikoff, Bordet, Landsteiner, Macfarlane Burnet, Porter, Dausset
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Host Defense Systems
A. Innate (Nonspecific) Immunity -
1. Skin & Mucous Membranes - First Line of Defense
a. Skin
b. Membranes
Respiratory Tract
Eyes
c. Stomach
d. Genitourinary
2. Immunological Surface Protective Mechanisms
a. Immunoglobulins A and E
IgE
IgA
3. Non-Ig Humoral Factors(Physiologic Barriers)
4. Neutrophil/Macrophage Functions - a. Phagocytosis
5. Inflammatory Response
B. Adaptive (Specific) Immunity
1. Characteristics
a. Recognition
b. Specificity
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c. Effector Response
d. Memory
e. Heterogeneous (Diversity)
2. Cells of the Immune System
a. Lymphocytes
B- Cells
T- Cells
b. Antigen Presenting Cells Macrophages & Others with MHC
3. Lymphocyte Functions
a. Humoral Response
b. Cell Mediated Response
Immune Mechanisms In Tissue Damage
Double Edge Sword
Type I Anaphylactic Type III Immune Complex
Type II Cytotoxic Type IV Delayed Hypersensitivity
.
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NONLYMPHOID CELLS OF THE IMMUNE SYSTEM
I. The Myeloid System
A. Granulocytic Series
1. Neutrophils
2. Eosinophils
3. Basophils
B. Platelets
C. Mast cells
II. Mononuclear-Phagocytic System
A. Monocytes
B. Macrophage
1. Structure
2.Location
3. Functions
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a. Phagocytosis
b. OtherHas surface receptorsSynthesize & secrete proteinsPromotes healing
c. Antigen Processing
d. Antigen Presentation
Th cell with interleukin 1
e. Activation - Both Tc cells and B cells
C. Dendritic Cells
1. Description -
a. Myeloid
b. Langerhans
c. Interstitial
d. Lymphoid
2. Follicular Dendritic Cells
3. Development
III. Lymphocytic System - 15-20% of peripheral WBC's
T-Cells- 70-90% B-Cells- remainderA. Function
B. Morphology
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LYMPHOID CELLS OF THE IMMUNE SYSTEM
I. The Lymphoid Cells
A. General Description
B. Morphology-
C. Stages of Development
1. Small Lymph------> Go, G1, S1, M
D. Life Span
E. Lymphocyte Surface Molecules
1. Antibodies
2. Major Histocompatibility Antigens (MHC)
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3. TCR - T receptor complex
4. CD Antigens
a. Kinds of Lymphocyte Receptors- Antigen
- Cytokine
-Antibody
-Complement
b. Lymphocyte Adherence Molecules-
II. B-Lymphocytes
A. Description
III. T- Lymphocytes
A. Description
B. Role of the Thymus
C. Mature Peripheral T-Cell Populations
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1. Naive T Cells
2. Effector Cells
a. Th
b. Tc
c. Ts
d. Tdth
3.Memory Cells
IV.Killer Cells and Natural Killer Cells
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ORGANS OF THE IMMUNE SYSTEM
I. Lymphoid System
A. Description
II. Organs of the Immune System
A. Primary
1. Thymus
a. Structure
Lobes
Cortex - Germinal Centers
Medulla
b. Function
2. Bone Marrow - Bursa of Fabricius equivalent
a. Structure
b. Function
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B. Secondary
1. Lymph Node
a. Structure
Cortex
Paracortex
Medulla
Germinal Centers
b. Function
2. Spleen
a. Structure
White Pulp
Germinal Centers
Red Pulp
b. Function
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3. Mucosal-Associated Lymphoid Tissue (MALT)
a. Structure & Location
M Cells
b. Function
III. Lymphocyte Circulation
A. Circulation Diagram
B. Circulation - Vessels
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ANTIGENS
Molecular Events
Antigens
Immunocompetent Cells
Membrane Events
Information Transfer
Nuclear Events
Cytoplasmic Events
Immune Molecules
Humoral
Cell Mediated
Definitions/Concepts
Antigens
Epitope
B-cell
T-cell
Hapten
Crossreactivity
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Heterophile
Mitogen
Antigen Classification
Chemical Basis
Complete
Incomplete
Common Antigens
Bacteria
Viruses
Blood Elements
Drugs
Organ Grafts
Autoantigens
Fetuses
Factors Influencing Immunogenicity
1. Antigen Foreigness
Graft
Xenograft
Allograft
Isograft
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Autograft
2. Antigen Complexity & Size
3. Catabolism/Degradability
4. Antigen Dose
5. Route of Immunization
6. Immunocompetence
7. Genetics
8. Nutritional Factors
Summary
1. The physical properties of the antigen2. The biological system3. The route of administration of the antigen4. The method of immunization5. The dose of the antigen
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IMMUNOGLOBULINSI. Immunoglobulins
A. General Descriptions
B. Basic Immunoglobulin Structure
1. AbbreviationsF - fragment, ususally obtained by digestionab- antibody-combining portionFc- crystallizable portionC - constant regionV - variable regionH - heavy chainL - light chain
2. Purified Molecule Visualized
3. Heavy Chain
4. Light Chain
C. Classes - 5
D. Immunoglobulin Variants - Antibody Heterogeneity
1. Isotypic variants
2. Allotypic variants
3. Idiotypic variants
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E. Basic Structure of Five Classes
1. IgG
2. IgD
3. IgE
4. IgA
5. IgM
F. Properties & Biological Activities
G . Subclasses 1.
2.
3.
H. B-cell receptors
I. The Immunoglobulin Superfamily
J. Monoclonal Antibodies
Problems
Production
Limitations
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COMPLEMENT
I. Definition:
A. Complement - An interrelated group of serum proteins that is maintained in a biologically inactive, native state and is enzymatically and sequentially activated by the combination of complement-fixing antibody with antigen or by other alternate substances. The essential feature is the sequential enzymatic cleavage of each complement component (C'1a is an exception). The system is designed to:
1. Lysis
2. Inhance phagocytosis
3. Participate in Inflammation
4. Remove immune complexes
II. Characteristics of Complement
A. Components
1. Classical
2. Alternate
3. Terminal
4. Control Proteins
B. Terminology
C. Physiochemical
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III. Classical Complement Pathway
A. Activation
B. Reaction Mechanisms
C. Steps in Reaction
IV. The Alternate Complement Pathway
A. Description
B. Activators
C. Reactions
V. Terminal Complement Pathway
A. Description
B. Reaction
VI. Regulation of the Complement System -
A. Labile
B. Inhibitors
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VII. Receptors for Complement A. Description
B. Receptors
VIII. Biological Consequences of Complement
A. Cell Lysis
B. Inflammatory Response
C. Opsonization
D Virus Neutralization
E. Removal of Immune Complexes
IX. Complement Deficiencies
A. Inborn Abnormalities
B. Acquired Abnormalities
1. Increased utilization
2. Decreased synthesis
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THE MAJOR HISTOCOMPATIBILITY COMPLEX
I. Location
A. Class I
B. Class II
C. Class III
II. Structure and Function
A. The Class I Genes and Proteins
1. Polymorphic
2. Co-dominate, allelic, inherited
3. -1, 2, 3
4. β - 2 Microglobulin
5. Function
B. The Class II Genes and Proteins
1. Two-peptide protein
2. Variation
3. Function
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ANTIGEN PRESENTATION
I. General Background
A. Self-MHC Restriction
B. APC Cells
C. Target Cells
II. Antigen Processing
A. Endogenous
B. Exogenous
1. Endocytosis
2. Phagocytosis
III. Antigen Presentation -
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T-CELL RECEPTOR (TCR) T CELL MATURATION, ACTIVATION, & DIFFERENTIATION
I. T-Cell Receptor (TCR)
A. TCR Structure
B. T-Cell Receptor Complex: TCR-CD3
C. T-Cell Accessory Membrane Molecules -
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T-Cell Maturation, Activation, and Differentiation
I. T-Cell Maturation
II. Thymic SelectionA. Selection of the TCR
1. Positive
2. Negative
III. T-Cell ActivationA. Peripheral Circulation
B. Antigen Encounter
C. Mechanism
D. Signaling Pathways
E. Co-Stimulatory Signal
F. Clonal Expansion vs. Clonal Anergy
G. Super Antigen
III. T-Cell Differentiation
A. Effector Cells
B. Memory Cells
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B-Cell Generation, Activation, & Differentiation
I. General Description
II. B-Cell MaturationA. Bone Marrow
1. Stages - Pro-B
2. Stages - Immature B
3. Selection
III. B-Cell Activation and Proliferation A. General Description
1. Site
2. Paracortex/Cortex
3. Antigen
B. Thymus-Dependent and Thymus-Independent Antigens
1. Properties
2. Thymus-Independent
3. Thymus - Dependent
C. Signaling
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IV. The Humoral Response
A. Primary
1. Description -
2. Characteristics -
B. Secondary
1. Description
2. Characteristics
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CYTOKINES
I. Cytokines
A. Function
1. Autocrine
2. Paracrine
3. Endocrine
B. Biological Activities
C. Interleukins
1. Interleukin 1
2. Interleukin 2
D. Interferons
1. α and β
2. γ
E. Tumor Necrosis Factors
1. Tumor necrosis factor - alpha
a. Trigger
b. Sequelae
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II. Secretion of Cytokines by Th
A. Th1 Subset
B. Th2 Subset
Leprosy -
III. Cytokine Receptors
A. Structures
B. Function
IV. Cytokine-Related Diseases
A. Bacterial Septic Shock
B. Bacterial Toxic Shock
C. Chagas' Disease
V. Therapeutic Uses of Cytokines
VI. Cytokines In Hematopoiesis
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LEUKOCYTE ACTIVATION AND MIGRATION
I. General
A. Lymphocyte Recirculation
B. Leukocyte Migration
C. Cell-Adhesion Molecules
1. Selectins/Mucins
2. Integrins/ICAMS - Ig Superfamily
D. Neutrophil and Lymphoycyte Extravasation - See online @ www.whfreeman.com/immunology6e
E. Lymphocyte Exravasation
1. High-Endotheial Venules
2. Homing of Lymphocytes
II. Mediators of InflammationA. Biologic Activity of Mediators
B. Types1. Chemokines
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2. Plasma Enzyme Mediators
a. Kinin System
b. Clotting System
c. Fibrinolytic System
d. Complement System
3. Lipid Inflammatory Mediators
a. Slow Reacting Substance of Anaphylaxis (Leukotriens)
b. Prostaglandins
c. Platelet Activating Factor
III. Acute Inflammatory Response
A. Causes of Inflammation
B. Hallmarks of Inflammation
C. Features of Inflammation
IV. Acute Phase (Local)
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A. Increased vascular permeability
B. Chemotaxis
C. Phagocytosis
V. Acute-Phase (Systemic) Response
A. Characteristics
1. Fever
2. Acute Phase Proteins
a. Example
C- Reactive
VI. Chronic Inflammation
A. Description
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CELL-MEDIATED CYTOTOXIC RESPONSES
I. Description
II. Effector ResponsesA. Cells involved
1. Specific Cells
2. Non-specific Cells
B. Categories of Cell Mediated Immunity
1. Direct Cytotoxic Response
2. Delayed-type Hypersensitivity Reactions
C. General Properties of Effector T-Cells
III. Cytotoxicity Involving Antigen-Specific Cytotoxic Tc
A. Antigen-specific cytoxicity
1. Description
2. Tc-Cell Generation
3. CTL-Mediated Destruction of Target Cells
4. Natural Killer Cell (NK) Mediated Destruction
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5. Antibody-Dependent Cell-Mediated Cytolysis
IV. Graft vs Host Disease
A. Description
B. Symptoms
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HYPERSENSITIVITY REACTIONS
I. Hypersensitivity
A. Definition
B. Types
1. Humoral (Immediate)
2. Cell Mediated (Delayed)
3. Gell & Coombs Classifications
II. Type I – Anaphylactic
A. Components
B. Systemic Anaphylaxis
1. Symptoms
2. Causes
3. Mechanism
4. Treatment
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C. Localized - Atopic Allergy
1. Description
2. Causes
3. Mechanisms
a. Food Allergy
b. Upper Respiratory
c. Lower Respiratory
4. Treatment
D. The Late Phase Reaction
E. Detection of Type I Hypersensitivity
III. Type II - Cytotoxic
A. Mechanism
1. Antibody Mediated Tissue Damage
2. Blockage of Normal Cell Function
3. Complement-Mediated Cell Lysis
4. Antibody Dependent Cell Mediated Cytolysis (ADCC)
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IV. Type III - Immune Complexes
A. Description
B. Localized
1. Arthus Reaction
C. Generalized
1. Serum Sickness
a. Symptoms
2. Others
V. Type IV - Cell Mediated (DTH)
A. Description
B. Primary (Sensitization Phase)
C. Secondary (Effector Phase)
D. Cytokines and Chemokines Involved
E. Protective Role of DTH
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F. Examples
1. Tb, Leprosy, Histo, Cocci
2. Contact Sensitivity
G. Detection
1. Tb, Histo, Cocci
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TOLERANCE & AUTOIMMUNITY
I. Definitions
A. Autoimmunity
B. Self-Tolerance
1. Central
2. Peripheral
3. Aptosis
II. Establishing and Maintaining Tolerance
A. Central
B. Peripheral
C. Peripheral Regulatory T-Cells
D. Sequestered Antigen
E Tolerance Failure
III. Proposed Mechanisms for Induction of Autoimmunity
A. Release of sequestered Antigen
B. Molecular Mimicry
C. Inappropriate Expression of Class II MHC Molecules
D. Polyclonal B-Cell Activation
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IV. Organ Specific Autoimmune Disease
A. Auto-Antibodies - Cell Surface Components
1. Stimulating - Grave's Disease
2. Blocking - Myasthenia Gravis
B. Direct Cell Damage - Auto-Antibodies
1. Sensitized T-cells + Auto-Antibodies Hashimoto's Thyroiditis
2. Auto-Antibodies - Goodpasture's Syndrome
V. Systemic Autoimmune Diseases
A. Auto-antibody/Antigen Complexes
1. Systemic Lupus Erythematosis
2. Rheumatoid Arthritis
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MHC AND TRANSPLANTATION IMMUNOLOGY
I. General Statements
A. Givens
1.
2.
3.
B. System Involved
C. Early Pioneers
1. Dausset2. Payne3. Terasaki
II. Major Histocompatility Complex
A. Gene
B. Locus
C. Biochemical Make-up of Transplantation Antigens
1. Class I
2. Class II
D. Alloantigenic Determinants
1. HLA SpecificitiesHLA - A, HLA - B , HLA - C
HLA - DR, HLA - DQ, HLA - DP
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E. Nomenclature
G. Immunogenetics
1. Phenotype
2. Haplotypes
3. Inheritance of HLA Antigens
III. Testing
A. Lymphocytotoxicity Testing
B. Mixed Lymphocyte Culture
C. Determining Genotypes
Example
IV. Transplantations
A. Organ and Cell Transplantations
. B. Effects of Matching
C. Mechanisms Involved in Graft Rejection
D. Clinical Manifestations of Graft Rejection
1. Antibody Mediated
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E. General Immunosuppressive Therapy
1. Mitotic Inhibitors
2. Fungal Metabolites
F. Specific Immunosuppressive Therapy
1. Antibodies
2. Signal Blocking
G. Immune Tolerance to Allographs
1. Privileged Site
2. Specific Tolerance
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IMMUNE RESPONSE TO INFECTIOUS DISEASE
I. Basic Definitions
A. Adaptive Immunity
1. Humoral
a. Actively Acquired
i. Natural
ii. Artificial
b. Passively Acquired
i. Natural
ii. Artificial
B. Innate Immunity
1. Barrier Cells
2. Phagocytic Cells
3. Mediator Cells
4. Acute Phase Response
5. Inflammation
6. Phagocytosis
II. Process of Phagocytosis A. Steps
1. Chemotaxis and Attachment
2. Ingestion
3. Killing
a. Non-Oxidative
b. Oxidative
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4. Digestion and Release
III. Immunity to Infectious Pathogens
A. Bacterial
1. Nonspecific
2. Specific vs Evasion Mechanisms
a. Attachment to host cells
b. Proliferation
c. Invasion of Host Tissue
d. Toxin Induced Damage to Host Cells
B. Viral
1. Nonspecific
2. Specific
3. Evasion
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C. Protozoa
1. Nonspecific
a. Species and genetic influences
2. Specific
3. Evasion
D. Helminths
1. Nonspecific
a. competition
2. Specific
a. IgE
E. Fungal Diseases
1. Innate
2. Acquired
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AIDS AND OTHER IMMUNODEFICIENCIES
I. General
A. Cells
1.
2.
3.
B. Derivation of Immunodeficiencies
1. Primary Immunodeficiency
2. Secondary - May be acquired
C. Distribution -
1. Phagocytic - 14%2. Humoral - 53%3. Cell-Mediated - 7%4. Combined - 23%5. Complement & Undeciphered - <3
II. PrimaryA. Phagocytic Cell Deficiencies
1. Cause
2. Diagnosis
3. Diseases
a. Reduction in Function
1.1 Chronic Granulomatous Disease
1.2 Chediak-Higashi
1.3 Bare Lymphocyte Syndrome
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b Reduction in Neutrophil Count
B. Humoral - Immunodeficiencies Involving B Lymphocytes
1. Diagnosis
2. Diseases
a. Bruton's Agammaglobulinemia
b. Common Variable Hypogammaglobulinemia
c. Hyper IgE - Job's Disease
d. Selective IgA Deficiency
C. T-Cell-Mediated Deficiencies
1. Diseases
a. DiGeorge's Syndrome
D. Combined B-Cell and T-Cell Immunodeficiencies
1. Diseases
a. SCID
b. Wiskott-Aldrich Syndrome
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c. Bare-lymphocyte Syndrome
E. Treatment
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III. Secondary Immunodeficiencies - AIDS
A. Epidemiology
B. Etiologic Agent
C. Transmission
D. Regulatory Genes
E. Laboratory Tests
1. Hematology
2. Serology
3. Antigen Tests
F. Pathogenesis
1. T-cells
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2. T-helper
3. B- Cells
G. Clinical Diagnosis
H. Treatment
I. Vaccines
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CANCER AND THE IMMUNE SYSTEM
I. General Information
A. Description & Terms
1. Benign
2. Malignant
3. Cancer
4. Metastasis
5. Embryonic origin
a. Carcinoma
b. Sarcoma
c. Leukemia & lymphoma
B. Properties of Cancer
1. Clonally Derived
2. Change in Cell Growth
3. Altered Tissue
4. Biochemical Changes
5. Disorganized Cytoskeleton
6. Chromosomal Abnormalities
II. Etiology
A. Chemical
B. X-Ray
C. Viruses
D. Human Oncogenes
III. Tumor Antigens
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A. General
1. TATAs - Tumor Associated Transplantation Antigens ( Inappropriate expression of embryonic gene)
a. Oncofetal Antigens
CEA
AFP
2. TSTAs - Tumor Specific Transplantation Antigens (Mutation generates new peptide in Class I MHC molecules)
a. Chemical or Physical
b. Virally induced
3. TATAS - Oncogene Proteins as Tumor Antigens - (Over expression of normal proteins).
IV. Tumor Immunity
A. General
B. Tc cells
C. NK cells
D. Macrophage
V. Tumor Evasion of the Immune System
A. Reduction In Class I MHC Molecules
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B. Modulation of Tumor Antigens
C. Immune Enhancement
D. Lack of Co-Stimulatory Signals
E. Immunodeficiency
VI. Cancer Therapy - Surgery - Radiotherapy-Chemotherapy - ImmunotherapyA. Surgery
B. Immunotherapy
1. Defined
2. Manipulation of Co-Stimulatory Signals
3. Monoclonal Antibodies
4. Enhancement of APC Activity
5. Cytokine Therapy
3/09
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