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2011-05-11 15:30:35
Immunology MS1

Immunology Lecture 5 Syllabus complete
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  1. Normal Blood Cell counts per microliter
    (Leukocytes, Lymphocytes, Neutrophils, Eosinophils,
    Basophils, Monophils)
    • Leukocytes 7400 (4500-11000)
    • Neutrophils 4400 (1800-7700)
    • Lymphocytes 2500 (1000-4800)
    • Monocytes 300 (0-800)
    • Eosinophils 200 (0-450)
    • Basophils 40 (0-200)
  2. Hematopoiesis
  3. Myeloid lineage
    • granulocyte/macrophage progenitor --> neutrophil, eosinophil, basophil, mast cell precursor, monocyte --> macrophages
    • megakaryocyte progenitor --> megakaryocyte --> platelet
    • erythrocyte progenitor --> erythroblast --> erythrocyte
  4. What cells are in the reticuloendothelial system?
    monocyte/macrophage series
  5. 3 functions of monocyte/macrophage series
    • engulf and digest RBC/microbes
    • make cytokines
    • process and present antignes to adaptive immune lymphocytes
  6. 5 types of macrophages
    • Kupffer cells
    • Alveolar macrophages
    • splenic macrophages
    • peritoneal macrophages
    • microglial cells
  7. cytokine stimulation triggers macrophage transition into ___
    antigen presenting cells (APC)
  8. Where are immature dendritic cells?
    blood and tissues
  9. What triggers dendritic cell activation?
    microbial PAMPs
  10. What do activated DC do?
    • secrete cytokines to activate both innate and adaptive immune systems
    • express cell surface molecules that activate naiive T cells
    • become APC for initiation of adaptive response
  11. lifespan of PMNs and macrophages
    • PMNs= short lived
    • macrophages= long lived
  12. 3 types of PMNs
    • neutrophils: highly phagocytic
    • eosinophils: antiparasitic granules
    • basophils: antiparasitic granules
  13. Mast cell function
    • allergic responses (histamine granules)
    • anti parasitic (worms)
  14. 2 calsses of lymphoid tissues
    • primary organs= generative, lymphocytes first express antigen receptors and mature
    • secondary organs= peripheral, lymphocyte responds to foreign antigens and develop
  15. 2 primary lymphoid organs
    • bone marrow: maturation of naiive B cells
    • Thymus: T cell maturation
  16. characteristics of mature B cell leaving bone marrow
    expression of single, unique antigen-specific receptor
  17. Thymus compartments
    • cortex: densely packed with thymocytes (T cell precursors)
    • medulla: mostly mature T cells with single antigen-specific receptor
  18. 3 steps to initiating adaptive response
    • cognitive phase: selection of lymphocyte with appropriate receptors by antigen in LN
    • activation phase: proliferation of antigen specific clones in LN
    • effector phase: differentiation into effector and memory cells in periphery
  19. what's the major mechanism by which antigen and activated DC presenting antigen travel from peripheral tissues into lymphatic tissues of the adaptive immune system
    lymphatic system
  20. lymph node structure
  21. Function of lymph node compartments
    medulla, cortex, paracortex, germinal center, marginal zone
    • cortex: mainly B cells
    • paracortex: T cells being activated by DC presenting antigens
    • germinal center: proliferating B cells within a follicle during immune response
    • marginal zone: B cells that are not part of the germinal center /c they are irrelevant antigens
  22. primary follicles vs secondary follicles within lymph nodes
    • primary follicles: no germinal centers
    • secondary follicles: contains germinal centers
  23. Spleen collects antigens from ____
  24. Structure of spleen
    • blood supply: single splenic artery pierces capsule at hilum and divides into arteriolar branches surrounded by trabeculae
    • white pulp: lymphocytes around arteriolar branches, analagous to lymph nodes (contains follicles and PALS)
    • follicles: B cells
    • PALS: periarteriolar lyphoid sheaths with T cells
    • red pulp: sinusoids with all blood cells
  25. 2 locationso f antigen delivery in spleen
    • marginal sinus via circulating dendritic cells
    • marginal zone via macrophage sampling
  26. Individuals without spleen is susceptible to which type of infection?
    encapsulated bacteria (pneumoccocci, meningococci) which require opsonization and phagocytosis for clearance.
  27. cutaneous immune system structures (image)
  28. cutaneous immune system cell population
    • keratinocytes: produce several cytokines for innate response and inflammation
    • Langerhan cells: immature DC in suprabasal epidermis; continuous meshwork that catch antigens entering thorugh skin; mature DC lose adherence to epidermis
    • intraepidermal lymphocytes (memory T cells)
    • resident macrophages in dermis
    • trafficking T lymphocytes in dermis
  29. 2 locations with mucosal immune system
    respiratory tract and GI tract
  30. Mucosal immune system characteristic
    • immune cells scattered in lamina propria
    • M cells: specialized epithelial cells that transcytose macromolecules from intestinal lumen into subepithelial tissue
    • efferent lymphatics only
  31. migration pattern of naiive and effector T lymphocytes
    Naiive T enter LN via HEV --> leave via eferent lymphatic vessel if no antigen --> enter another LN --> encountering antigen allows differentiation into effector T and proliferation --> exit via efferent lymphatic then thoracic duct --> exits peripheral blood vessel into tissue
  32. homing receptors and addressins for naive T cell to high endothelial venule
    • homing receptor: L-selectin
    • addressin: CD34, GlyCAM-1
  33. homing receptors and addressins for naive T cell to mucosal endothelium
    • L-selectin
    • MAdCAM-1
  34. Steps of lymphocyte entry through HEV
    • rolling: L-selectin binds GlyCAM-1 and CD34
    • activation: CCL21 (chemokine on HEV) binding to CCR7 (receptor on T cell) activates LFA-1
    • tight binding: activated LFA-1 binds to ICAM-1
    • diapedesis
  35. homing receptors in effector T cells
    • increased expression of VLA-4 bind to VCAM-1
    • increased expression of LFA-1 bind to ICAM-1
    • L-selectin decrease
  36. Differentiation to mucosal homing lymphocytes
    • Naiive T cells activated by antigens in mucosal system differentiate
    • express alpha4:beta7 integrin homing receptor and CCR9 chemokine receptor
  37. Differentiation of skin-homing lymphocytes
    • CLA (cutaneous lymphocyte antigen) binds E-selectin on surface of cutaneous endothelium
    • CCR4 (chemokine receptor) interacts with CCL17 (endothelial chemokine)
    • once in dermis, CCR10 (receptor) interacts with CCL27 (chemokine secreted by active keratinocytes)
  38. Homing specificity of:
    L-selectin binding to CD34, glyCAM1, sialyl Lewis-X sulfated carbohydrates
    naive lymphocytes to lymph nodes
  39. Homing specificity of:
    L-selectin binding to MAdCAM
    naive lymphocytes to Peyer's patches
  40. Homing specificity of:
    alpha4/beta7 integrin binding to MAdCAM and VCAM1
    • naive lymphocytes to Peyer's patches
    • memory effector celsl to lamina propria of GI tract
  41. Homing specificity of:
    CLA binding to E-selectin and P-selectin
    memory effector cells to skin
  42. Homing specificity of:
    VLA-4/LFA-1binding to VCAM-1, ICAM-1
    activated lymphoblasts and memory effectors to site of inflammation
  43. interactions of the innate and adaptive immune systems