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
Edema
Fluid in alveolus/tissue interstitum
Types of exudates
- Serous (few cells, clear)
- Purulent (pus; many inflam. cells)
- Hemorrhagic (RBCs, capillary dmg)
- Fibrinous (fibrin layer deposition)
Leukocyte migration across vessel wall process
Dilation slows blood, allowing margination
1. Margination when dilation occurs
2. Rolling (selectins, integrins)
3. Tight adhesion (integrins)
4. Extravasation across wall
Neutrophil chemotactic factors
- IL-8 CXC chemokines, C5a, PAMPs, PAF, leukotriene B4 (LTB4)
- Attracts PMNs to site of inflam.
- Also important for lymph node T/B migration
Systemic effects of acute inflammation
- Fever (cytokines to hypothalamic thermoregulatory center)
- Leukocytosis (colony-stim. factors to bone marrow for leukocyte release)
- Tachycardia, tachypnea
- Acute phase reactants (IL-6 to liver protein synth.
2 important functions of acute inflammation
- Recognize
- Remove
Types of bacterial killing by phagocytic cells
- EC traps
- IC killing (phagocytosis, engulfment, killing/degradation)
EC traps for bacterial killing
Neutrophil NETs (chromatin/protein strands)
Opsins
Bind to pathogens to target for destruction; complement + ABs
Phagocytosis process
- Recognition w/ phagocyte receptors
- Engulfment (phagosome creation)
- Degradation (phagolysosome; phagocyte oxidase activation)
Phagocyte oxidase
Activation triggers oxidative burst reaction for ROS generation:
- Superoxide
- H2O2
- OH-
- OONO- (peroxinitrite)
Detrimental effects of inflammation
Tissue injury due to overinflam.
- ROS/protease release
- Inappropriate coagulation
