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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)
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Myeloid lineage
- granulocyte/macrophage progenitor --> neutrophil, eosinophil, basophil, mast cell precursor, monocyte --> macrophages
- megakaryocyte progenitor --> megakaryocyte --> platelet
- erythrocyte progenitor --> erythroblast --> erythrocyte
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What cells are in the reticuloendothelial system?
monocyte/macrophage series
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3 functions of monocyte/macrophage series
- engulf and digest RBC/microbes
- make cytokines
- process and present antignes to adaptive immune lymphocytes
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5 types of macrophages
- Kupffer cells
- Alveolar macrophages
- splenic macrophages
- peritoneal macrophages
- microglial cells
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cytokine stimulation triggers macrophage transition into ___
antigen presenting cells (APC)
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Where are immature dendritic cells?
blood and tissues
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What triggers dendritic cell activation?
microbial PAMPs
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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
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lifespan of PMNs and macrophages
- PMNs= short lived
- macrophages= long lived
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3 types of PMNs
- neutrophils: highly phagocytic
- eosinophils: antiparasitic granules
- basophils: antiparasitic granules
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Mast cell function
- allergic responses (histamine granules)
- anti parasitic (worms)
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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
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2 primary lymphoid organs
- bone marrow: maturation of naiive B cells
- Thymus: T cell maturation
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characteristics of mature B cell leaving bone marrow
expression of single, unique antigen-specific receptor
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Thymus compartments
- cortex: densely packed with thymocytes (T cell precursors)
- medulla: mostly mature T cells with single antigen-specific receptor
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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
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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
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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
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primary follicles vs secondary follicles within lymph nodes
- primary follicles: no germinal centers
- secondary follicles: contains germinal centers
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Spleen collects antigens from ____
blood
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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
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2 locationso f antigen delivery in spleen
- marginal sinus via circulating dendritic cells
- marginal zone via macrophage sampling
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Individuals without spleen is susceptible to which type of infection?
encapsulated bacteria (pneumoccocci, meningococci) which require opsonization and phagocytosis for clearance.
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cutaneous immune system structures (image)
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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
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2 locations with mucosal immune system
respiratory tract and GI tract
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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
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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
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homing receptors and addressins for naive T cell to high endothelial venule
- homing receptor: L-selectin
- addressin: CD34, GlyCAM-1
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homing receptors and addressins for naive T cell to mucosal endothelium
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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
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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
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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
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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)
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Homing specificity of:
L-selectin binding to CD34, glyCAM1, sialyl Lewis-X sulfated carbohydrates
naive lymphocytes to lymph nodes
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Homing specificity of:
L-selectin binding to MAdCAM
naive lymphocytes to Peyer's patches
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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
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Homing specificity of:
CLA binding to E-selectin and P-selectin
memory effector cells to skin
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Homing specificity of:
VLA-4/LFA-1binding to VCAM-1, ICAM-1
activated lymphoblasts and memory effectors to site of inflammation
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interactions of the innate and adaptive immune systems
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