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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.
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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. 3. It is important to learn the basics, the “party line.” There is no party line; it keeps changing.
“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 what questions to ask.
Time Course of thePrimary Immune Response Innate immunity Acquired immunity
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 nodes and spleen Step 4. Lymphocytes exit the lymph nodes and spleen and become effector lymphocytes--they produce antibody (B cells) or become competent to kill (CD8+ T cells)
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.
Antibody (Ig) and TCR are the Only Genes that Undergo Somatic Cell Recombination Antibodies: Secreted or Transmembrane (BCR) TCR: Transmembrane
What Happens in the Thymus? Ordered TCR gene rearrangement and TCR expression Ordered expression of surface molecules: CD2 CD4 and CD8 CD3 and the TCR Thymocyte Education: Selection of the T cell repertoire Negative Selection Positive Selection
Thymic Development Bone marrow Periphery “Educated, but naïve”
The Primary Immune Response--Input (APCs) and Output (Lymphocytes et al.)
Functional Anatomy of a Lymph Node Ag-loaded APC Naïve T-cell Effector or Memory T-cell
The Clonal Selection Theory Naïve state Ag encounter Clonal expansion
Contact Between the TCR and MHC/peptide:Not All Peptides are Created Equal
Contact Between the TCR and MHC/peptide:Not All MHC Molecules are Created Equal Polymorphisms
The “Fit” Between MHC Moleculesand Peptide Defines MHC Restriction Polymorphisms within the MHC account for the variability of the immune response between individuals
T Cell Receptor for Antigen (TCR):One TCR is Specific for One Antigen Antigen Recognition T cell Activation
The B Cell Receptor for Antigen (BCR) Two Major Functions: 1. Bound antigen is internalized and presented to T cells. 2. Bound antigen triggers signals in the B cell to proliferate and differentiate.
The Two-Signal Theory of T-cell Activation 2 1 1 2 No response or Anergy Activation No response APC = Antigen-presenting cells TCR = T-cell receptor for antigen DC = Dendritic cell CD80 = Co-stimulatory receptor
Two Major Functional T Cell Subsets CD4+ T cell CD8+ T cell z z z z g g d d e e Lck Lck CD3 CD3 C C a b C C a b TCR TCR V CD4 b V b V a V a CD8 peptide peptide MHC I MHC II APC APC (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
Major Lymphocyte Subsets in Peripheral Blood and Selected Effector Functions T cells B cells gd CD8 CD4 Ab production Cytotoxicity Cytotoxicity Help to B cells Ag presentation IFN-g secretion Help to CD8 T cells Cytokine secretion Macrophages activation Innate immunity
Regulation of the Immune Response:a Conceptual View Immunity Tolerance Activation Suppression Autommunity Immunodeficiency