Lecture 1: Inflammation I Flashcards
Types of inflammation
- Acute (0-7 days)
- Subacute (7-30 days)
- Chronic (30+ days)
Inflammation
Host response to injury or insult
Types of leukocytes (WBCs)
- Granulocytes (PMNs, eosinophils, basophils)
- Lymphocytes (T, B, NK)
Types of T cells
- CD4+ T
- Th1: pro-inflam.; IL-1/6, TNF, IFNγ
- Th2: IL-4/5/13
- Th17: recruit PMNs, IL-17
Other inflammatory cells
- Monocytes/macrophages
- APCs
- Fibroblasts (scarring)
M1 vs M2 macrophages
Aka classical vs alternative activation; microbicidal vs remodeling/repair
M1: ROS, NO, lysozymes, pro-inflam. (IL-1/6/12)
M2: fibrosis, repair, anti-inflam. (IL-10, TGFβ)
Cell-derived acute inflam. molecules
Preformed in storage granules or synthesized rapidly de novo
- Histamine
- Prostaglandins
- Cytokines
Plasma protein-derived acute inflam. molecules
Complement molecules; mainly formed by liver, present in inactive form
Cardinal signs of inflammation
- Rubor
- Calor
- Tumor
- Dolor
Steps in acute inflammation
- Blood vessel changes to increase flow
- Microvascular changes to allow protein/cells to leave vessels (PMNs = hallmark inflam. cell)
- Emigration, accumulation, activation of leukocytes
Acute inflammation blood vessel changes
- Dilation due to resident macrophage mediator release
- Causes edema, cell recruitment, hyperemia
General characteristics of inflammatory mediators
- Stim. other cells to release secondary effectors and amplify/oppose a given response
- Very quickly destroyed or removed; limited time/space activity
Types of vasodilators
- Vasoactive amines
- Arachidonic acids from COX enzymes
- NO
- Bradykinin
- Platelet Activating Factor (PAF)
Vasoactive amines
Histamine, serotonin
- Earliest mediators (preformed granules)
- Release by mast cells + platelets
- Stim. by physical injury, Ab binding to mast cells, complement fragments C3a, C5a
- Cause arteriole dilation/increased permeability
Arachidonic acid metabolies
Prostaglandins, leukotrienes, lipoxins
- From PLs in cell membrane (phospholipase A2 releases AAcids)
- From COX enzyme (prostaglandins, thromboxane; aspirin inhib. COX)
- From 5-lipoxygenase (leukotrienes, lipoxins)
Platelet Activating Factor
- From membrane PLs
- Created by leukocytes, mast cells, endothelial cells, platelets
Effects: - Platelet aggregation
- Vasodilation @ low levels
- Leukocyte oxi. burst, adhesion, chemotaxis, degranulation
Nitric oxide
- Relaxes smooth muscle to cause vasodilation
- Bacterial killing
- From NO synthetase
Plasma protein inflammatory mediators
- Activated by cleavage e.g. bradykinin by kallikrein cleavage
Microvascular changes that allow proteins/cells out of vessels
Endothelial cell retraction (histamine, PGs, NO, bradykinin; dual effect w/ vasodilation)
Complement
- Soluble proteins + receptors present in larger inactive forms
- Cleavage activation by classical, alternative, lectin paths
- MAC lysis, C3b opsonization, C5a/C3a inflam./leukocytes
Complement actions
C3a, C5a anaphylatoxins:
- Histamine mast cell release
- Vasodilation, permeability
C5a:
- Chemotaxis esp. PMNs
- Activate lipoxygenase for AraAs
C3b:
- Opsonization
Transudate
Fluid leaving vessels due to hydrodynamics, low in cells/protein content
Exudate
Fluid escaping vessels due to inflam.; high cell/protein content
Effusion
Escape of fluid to defined cavity; drainable
