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52 Cards in this Set
- Front
- Back
Polymorphonuclear neutrophils (PMNs)
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-represent 50-60% of total circulating leukocytes
-devel in BM takes about 2 weeks -healthy adult 10^11/day, 10^12/day in inflam conditions; 1/2 life 4-10 h, in tissue 1-2 days |
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What are the 6 morphological stages of PMNs?
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1. Myeloblast
2. Promyeloblast 3. Myelocyte 4. Metamyeloctye 5. Non-segmented (band)neutros 6. Segmented (mature cell) |
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What are the 3 main types of Neutrophil granules?
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1. Primary (azurophil)
2. Secondary (specific) 3. Tertiary (small storage) |
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What do Primary (azurophil) granules contain?
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1. Myeloperoxidase
2. Defensins 3. Elastase 4. Phospholipase A2 |
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What do Secondary (specific) granules contain?
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1. Lysozyme
2. Lactoferrin 3. Collagenase 4. Phospholipase A2 |
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What do Tertiary (small storage) granules contain?
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1. Gelatinase
2. Cathespins 3. Glucoronidase 4. Mannosidase |
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Monocytes
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-originate in BM
-possess migratory, chemotactic, and phagocytic activities as well as PRRs and receptors for opsonins such as IgG, Fc domains, CRP, C3b |
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Macrophages
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-possess migratory, chemotactic, and phagocytic activities to a greater extent than monocytes
-possess similar receptors |
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What are the 4 types of normal macrophages?
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1. Histiocytes of CT
2. Kupffer's cells of the liver 3. Alveolar macrophages 4. Pleural and peritoneal macros |
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What are M1 macrophages?
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-inflammatory macrophage
1. aggressively destroy micros and tumor cells 2. Release proinflamm cytokines 3. Process and present Ags |
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What are M2 macrophages?
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-inflammatory macrophage
1. Remove dead/dying cells 2. Promote angiogenesis 3. Promote tissue remodeling 4. May be involved in tumor cell survival |
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Mast cells
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-dev in BM from myeloid precursors
1. From CT whose granules contain heparin 2. Associated with mucosal surfaces of resp and GI system which are smaller and with granules that contain chondroitin sulfate instead |
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Immune mediated (Type 1 hypersensitivity) degranulation
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IgE which is cytophilic for mast cells and basophils binds by means of its Fc domain
-Ag binding that results in cross linking of IgE molecules triggers degranulation |
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Nonimmune mechanisms of degranulation
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1. Physical injury
2. Frags of the C (C3a and C5a) 3. Toll receptors binding PAMPS 4. Leukocyte derived histamine releasing proteins 5. Neuropeptides (Sub P) 6. Cytokines |
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What are 3 types of production of other inflammatory mediators?
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1. Prostaglandins and leukotrienes
2. Cytokines, esp TNF 3. Platelet activating factor (PAF) |
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How are basophils similar to mast cells?
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-cytophilic for IgE, granules contain heparin, histamine, and serotonin
-they syn similar secondary mediators of prostaglandins, lukotrienes, PAF, and cytokines |
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How are basophils different from mast cells?
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1. basophils are normally found in circulation
2. arise from different BM progenitor cells 3. follow diff maturation pathways 4. synthesize significant amounts of IL-4 |
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What is a major role of IL-4?
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-The development of Th2 type immunity (humoral)
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Eosinophils
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-characteristic of IgE mediated rxns
-Type 1 hypersensitivities -Primary defense against fungi, protozoa, parasitic worms, and pathogens that are too large to consume by endocytosis |
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What do eosinophils produce?
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-prostaglandins, leukotrienes, and various cytokines such as IL-1, IL-6, IL-8, and TNF
-have granules that contain hydrolytic enzs and MBL and cationic protein |
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Major basic protein (MBL)
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-toxic to parasites
-also toxic to other cells, plays a role in airway damage in asthma -cytotoxic to tumors -modulate allergic inflam by releasing enzymes that breakdown hist and leukotrienes |
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NK cells
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-lymphocytes of null cells, part of innate immunity
-receptors called killer inhibitory receptors (KIRs) that recognize class I MHC, binding results in inhib of killing |
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What does NK killing involve?
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-release of perforins
-granzymes--> enter target cell thru pores to activate apoptosis |
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Activated NK cells are major sources of?
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cytokines such as IFN-Gamma and TNF
-also participates in Ab dependent cell cytoxicity (ADCC)--> killing of cells, including bact, bound with surface Abs |
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Platelets
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-play a primary role in hemostatis involving the formation of the hemostatic plug and initiation and regulation of clot formation
-sources of inflammatory mediators, vasoact substances |
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What are the 4 dense or delta granules?
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1. Histamine
2. Serotonin 3. Ca 4. ADP |
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What are alpha granules?
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1. Fibrinogen adn various other clotting factors
2. Platelet derived growth factor--> fibroblast prolif and act in repair 3. Transforming growth factor beta (TGF-B)--> epithelial and fibroblast development |
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What are 3 ways that platelet adherence, aggregation and degranulation occur?
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1. contact w/ damaged endo cells
2. contact w/ collagen following vascular injry 3. with thrombin after act of coagulation system -release of vasoact mediators serotonin & hist* (Neg amounts) |
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What do E and P selectins on endothelial cells reversibly bind?
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-leukocyte glycoproteins
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What are leukocytes activated by?
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-IL-1, IL-8, PAF and C5a
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Vascular Cell Attachment Molecule-1 (VCAM-1) on endothelial cells bind to?
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Very Late Activation - 4 (VLA-4)
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Intercellular Attachment Molecule-1 (ICAM-1) on endo cells bind to?
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1. Leukocyte Function Associated molecule-1 (LFA-1)
AND/OR 2. Myelin associated glycoprotein-1 (Mac-1) |
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Emigration (diapedesis, transmigration)
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-by ameboid motion btwn endo cells at the intercellular junctions
-PECAM-1 is maj protein of process -present on both act leukocytes and endothelial cells |
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Intravascular activation of Leukocytes
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-PRRs when bound to PAMPs
-chemotactic factors, esp IL-8 that result in full expression of leukocyte cell surface integrins |
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Extravascular activation of Leukocytes
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PMS are stimulated to undergo:
1. Degranulation and release of lysosomal contents 2. Gen of the oxidative burst 3. Production of eicosanoids 4. Production of cytokines |
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Unenhanced attachment in Endocytosis
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-involves recognition of PAMPs such as peptidoglycan, techoic acids, lipopolysch, mannans, glucans, by surface membrane PRRs
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Enhance attachment (opsonization)
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-moleucles such as C3b, CRP and Abs IgG and IgM that attacht to and coat microbial surfaces
-phag cells have surface receptors for these molecules, so serve as points of enhanced attachement, facilitating endocytosis |
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Oxygen dependent mechanism of killing
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-involves a resp/oxid burst characterized by a sudden increase in O2 consumption w/ the production of toxic reactive O2 metabolites
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What are 4 toxic reactive O2 metabolities?
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1. Superoxide (O2-)
2. Hydrogen peroxide (H2O2) 3. Hypochlorous acid (HOCL) 4. Hydroxyl radical (OH) |
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What are 5 oxygen independent mechanisms of killing?
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1. Lysosomal hydroolytic enzymes
2. Bactericidal/permeability increasing protein 3. Defensins 4. Lactoferin 5. Lysozyme (G- bact resistant to its actions) |
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Digestion
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1. Lysosomes (primary) w/ hydrolytic enzymes fuse w/ phagosome to form the phagolyxosome (secondary lysosome)--> digestion
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What are 4 types of tissue damage that can be caused by leukocytes?
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1. Cell death
2. Frustrated phagocytosis 3. Regurgitation 4. Autoimmune disease |
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Frustrated phagocytosis
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attempts at phagocytosing targets that cannot be ingested often result in degranulation adn release of damaging substance into tissues
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Leukocyte defects
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-functional defects may affect the mechanisms of adhesion, emigration, chemotaxis, phagocytosis, or microbial killing
-characterized by overwhelming infx |
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What are 5 examples of inherited leukocyte defects?
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1. Chronic granulomatous disease
2. Chediak-Higashi Disease 3. Leukocyte Adhesion Deficiency 4. Lazy Leukocyte Syndrome 5. Myleoperoxidase Deficiency |
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Chronic ganulomatous disease
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microbial killing defect due to lack of NADPH oxidase necessary to produce H2O2 and the superoxide radical
-autosomal recessive and X-linked |
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Chediak-Higashi Disease
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-dysfunction of the microtubules resulting in poor chemotaxis and failure of the lysosomes to fuse w/ phagosomes
-Autosomal recessive |
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Leukocyte Adhesion Deficiency
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Adhesion molecule deficiencies that interfere w/ cell adhesion prior to emigration
-autosomal recessive |
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Lazy Leukocyte Syndrome
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-cytoskeletal defects that interfere w/ cell movement including chemotaxis
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Myeloperoxidase Deficiency
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defect in microbial killing due to the lack of production in HOCL
-since other mechanisms compensate for this defect, ti is the least serious in nature |
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Reactive Lymphadentis
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enlarged lymph nodes that are the result of delivery of APCs to the nodes by lymphatic circulation
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What are 4 possible outcomes of acute inflammation?
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1. Resolution
2. Regeneration 3. Non-function (fibrous) repair 4. Chronic inflammation |