Inflammation Path Flashcards
Acute vs chronic inflammation
Acute: neutrophils + edema
- seconds initiation days duration
Chronic: macrophages/ lymphocytes + repair
Inflammation
Vascular response to injury/stress leading to the accumulation of protein rich fluid and activate leukocytes to tissue
Three components of acute inflammation
Vasodilation (seconds)
Increased permeability (minutes)
Migration of neutrophils (minutes - hours)
Ex/trans/purulent exudate
Transudate: mostly water, oncotic shift (HTN, starvation) low specific gravity (< 1.020)
Exudate: water, protein, cell debris (s.g. > 1.020)
Purulent exudate: exudate with neutrophils and apoptotic debris
Mechanisms of increased vascular permeability
- Gaps in venules due to endothelial contraction
- Endothelial injury (punching holes)
- Leukocyte adhesion and damage of endothelium in venules and capillaries
- transcytosis via interconnected vesicles and vacuoles (VEGF mediated)
Extravisation of leukocytes
Adhesion via P-selectins stored in weible pilade bodies (released by histamine and thrombin, and synthesized because of the signal IL-1 and TNF signal from macs) in endothelium binding sialyated gptns, and ICAMs on endothelium binding integrins (CD54). Chemokines released from tissue at sight of injury bind leukocytes and increase integrin avidity. Increase permeability allows diapedesis through capillary wall.
Chemotaxis: endogenous, exogenous
Exogenous: bacterial products
Endogenous: C5a, LTB4, cytokines (IL5-eosinophils, IL8-eosinophils and basophils, IL17 - attracts monocytes/neutrophils)
CD14
LPS receptor
CD31
Platelet adhesion molecules
CD44
Leukocyte to ECM binding
CD54
Integrin
IL1-5
1-Hot 2-T-cell proliferation 3-Bone marrow stimulation st 4-E (IgE) 5-A (IgA) k
3 steps in phagocytosis
Attachment: receptor binding
Engulfment: phagosome IP3/DAG
Destruction: phagolysosomes (MPO HOCl OH OONO)
Oxygen independent killing
Lysozyme, MBP, acid hydrolase
LAD 1/2
1 beta chain of integrin sect
2 lack of Sialyated oligosaccarides (no fucosyl transferase)
XLCGD/CGD
XL: membrane component of oxidative burst missing (NADPH oxidase defective)
Normal: cytoplasmic Ox burst missing (NADPH oxidase defective)
MPO deficiency
MPO- H2O2 halide killing defective
Chediak-Higasi syndrome
Defective microbial liking due to ineffective lysosomal docking/fusing
Leukopenia
Bone marrow suppression
Acquired Adhesion/chemotaxis defect
DM, cancer, sepsis, chronic dialysis
Acquired defective phagocytosis and microbiocidal activity
Leukemia, anemia, sepsis, DM, malnutrition premature neonates
Chemical mediators of inflammation
Histamine, serotonin, lysozymal act, eicosenoid derivatives, factor XII -> kinins, clotting factors and compliment
Azeurophilic granules/specific granules
Azeuophilic: Contain myeloperoxidase
Specific: lactoferrin
Sources of histamine: 3
Basophils, mast cells, platelets
- vasoactive amine H1 release, H2 negative feedback reduce.
Compliment components
C3a, C5a anaphalaxins
C5a is strongly chemotactic for neutrophils
C3b fixes compliment
C5b MAC
Thrombin in inflammation
Binds PAR-1 which is proinflammatory
NO in inflammation
Paracrine: seconds duration
Results in vasodilation -> contributes to margination
iNOS also contributes to microbiocidal activity producing peroxynitrite (OONO)
A.C.E.
Vitamins A, C and E reduce free radicals
Vasodilation Vascular permeability Chemotaxis Fever Pain Tissue damage
NO, histamine, PGE
Histamine, serotonin, C3,C5a, Bradykinin, PAF
TNF, ILs,
IL-12
Secreted by MACS; convert naive CD4 T cells into active TH1 cells.
- happens in process to granuloma formation
Granulomatous inflammation
Caseating; TB, fungus, syphillis
- langhans cells, central area of necrosis
Non-caseating; mycobacterium, sarcoidosis, many other infections
Serous inflammation
Bullous, watery filled vesicles with few inflammatory cells