immunology course-general principles
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Immunology Course-General Principles. Repetition is good, especially in different contexts. As good students, you are accustomed to mastering “the syllabus.” At least in this course, you can’t. The syllabus is an illusion, it does not truly exist. - PowerPoint PPT PresentationTRANSCRIPT
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1. Repetition is good, especially in different contexts.
2. As good students, you are accustomed to mastering “the syllabus.”At least in this course, you can’t. The syllabus is an illusion, itdoes not truly exist.
3. It is important to learn the basics, the “party line.”
4. There is no party line; it keeps changing.
Immunology Course-General Principles
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“Do I know the material?”
Simple test to determine whether you have mastered the material:
If you can explain the underlying concepts to the naïve (but motivated)student, you’re heading in the right direction. Therefore: learn whatquestions to ask.
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Immunology--The Whirlwind Tour
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Time Course of thePrimary Immune Response
Innate immunity
Acquired immunity
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Ontogeny of the Acquired Immune System
Step 1. Lymphocytes develop in the bone marrow and thymus
Step 2. Naïve lymphocytes circulate in the blood and lymph
Step 3. The primary immune response occurs in the lymph nodesand spleen
Step 4. Lymphocytes exit the lymph nodes and spleenand become effector lymphocytes--they produce antibody (B cells) or become competent to kill (CD8+ T cells)
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Stages in the Development of a Primary Immune Response
Step 1. The immune repertoire develops Lymphocytes develop early in life in the 1° lymphoid organs (bone marrow and thymus) and are competent to respond to a broad array of antigens. This process is first stochastic in nature and then becomes regulated by the MHC through positive and negative selection.
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Ig Maturation
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Antibodies: Secreted or Transmembrane (BCR)
TCR: Transmembrane
Antibody (Ig) and TCR are the Only Genes that Undergo Somatic Cell Recombination
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Journey of a B Cell
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Ordered TCR gene rearrangement and TCR expression
Ordered expression of surface molecules:CD2CD4 and CD8CD3 and the TCR
Thymocyte Education: Selection of the T cell repertoireNegative SelectionPositive Selection
What Happens in the Thymus?
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Thymic Development
Periphery
Bone marrow
“Educated, but naïve”
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What Happens During aPrimary Immune Response?
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The Primary Immune Response--Input (APCs) and Output
(Lymphocytes et al.)
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Three Types of APCs
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The Itinerant Dendritic Cell
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Functional Anatomy of a Lymph Node
Ag-loadedAPC Naïve
T-cell
Effector orMemory T-cell
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The Clonal Selection Theory
Naïve state
Ag encounter
Clonal expansion
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Functions of MHC I and II
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N
1
2
Structure of Peptide-binding Class I MHC Domains
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Contact Between the TCR and MHC/peptide:
Not All Peptides are Created Equal
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Contact Between the TCR and MHC/peptide:
Not All MHC Molecules are Created Equal
Polymorphisms
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The “Fit” Between MHC Moleculesand Peptide Defines MHC
Restriction
Polymorphisms within the MHC account forthe variability of the immune response between individuals
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AntigenRecognition
T Cell Receptor for Antigen (TCR):One TCR is Specific for One Antigen
T cellActivation
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1. Bound antigen is internalizedand presented to T cells.
2. Bound antigen triggers signals in the B cell to proliferate anddifferentiate.
The B Cell Receptor for Antigen (BCR)
Two Major Functions:
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The “Immunologic Synapse”
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The Two-Signal Theory of T-cell Activation
APC = Antigen-presenting cellsTCR = T-cell receptor for antigenDC = Dendritic cellCD80 = Co-stimulatory receptor
2 1 1 2
No responseNo response
or AnergyActivation
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V
C C
V
peptide
CD3
TCRCD4
MHC II
V
C C
V
CD3
TCR
MHC I
CD8
(1) Interacts with MHC class II expressing cells (APCs)
(2) Helps B cells to synthesize antibody(3) Induces and activates macrophages(4) Secretes cytokines
(1) Interacts with MHC class I-expressing cells (all nucleated cells)
(2) Kill MHC class I-expressing target cells(3) Secretes cytokines
CD4+ T cell CD8+ T cell
peptide
Two Major Functional T Cell Subsets
LckLck
APC APC
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CD4+ T Cells Activate Macrophages and B cells
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CD8+ CTLs Kill Viral-infected Cells
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B cells CD8 CD4
Ab production Cytotoxicity Cytotoxicity Help to B cellsAg presentation IFN- secretion Help to CD8 T cells
Cytokine secretion Macrophages activationInnate
immunity
T cells
Major Lymphocyte Subsets in Peripheral Blood and Selected Effector Functions
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ImmunityImmunity Tolerance Tolerance
AutommunityAutommunity ImmunodeficiencyImmunodeficiency
Activation Suppression
Regulation of the Immune Response:
a Conceptual View
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Systemic Lupus Erythematosis (SLE): AnAutoimmune Disease
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Clinical Manifestations of Rheumatoid Arthritis