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Transcript
Immunology Course-General Principles 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, it does not truly exist. 3. It is important to learn the basics, the “party line.” 4. 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. Immunology-The Whirlwind Tour Time Course of the Primary 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. Ig Maturation Antibody (Ig) and TCR are the Only Genes that Undergo Somatic Cell Recombination Antibodies: Secreted or Transmembrane (BCR) TCR: Transmembrane Journey of a B Cell 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 QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. “Educated, but naïve” What Happens During a Primary Immune Response? The Primary Immune Response-Input (APCs) and Output (Lymphocytes et al.) Three Types of APCs The Itinerant Dendritic Cell 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 Functions of MHC I and II Structure of Peptide-binding Class I MHC Domains a1 N a2 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 Molecules and 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 “Immunologic Synapse” QuickTime™ and a Sorenson Video 3 decompressor are needed to see this picture. The Two-Signal Theory of T-cell Activation 2 No response 1 No response or Anergy APC = Antigen-presenting cells TCR = T-cell receptor for antigen DC = Dendritic cell CD80 = Co-stimulatory receptor 1 2 Activation Two Major Functional T Cell Subsets CD4+ T cell Lck z z g d e Ca Cb CD4 Va CD8+ T cell Vb MHC II Lck CD3 TCR Ca Cb CD8 peptide 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 z z g d e Va Vb MHC I CD3 TCR peptide APC (1) Interacts with MHC class I-expressing cells (all nucleated cells) (2) Kill MHC class I-expressing target cells (3) Secretes cytokines CD4+ T Cells Activate Macrophages and B cells CD8+ CTLs Kill Viral-infected Cells Major Lymphocyte Subsets in Peripheral Blood and Selected Effector Functions T cells gd B cells Ab production Ag presentation CD8 Cytotoxicity Cytotoxicity IFN-g secretion Innate immunity CD4 Help to B cells Help to CD8 T cells Cytokine secretion Macrophages activation Regulation of the Immune Response: a Conceptual View Immunity Tolerance Activation Suppression Autommunity Immunodeficiency Systemic Lupus Erythematosis (SLE): AnAutoimmune Disease Clinical Manifestations of Rheumatoid Arthritis