Flashcards in Inflammation 2 Deck (17):
WHAT ARE THE CELLULAR EVENTS IN THE INFLAMMATORY RESPONSE?
Movement of leukocytes to site of injury.
Movement of leukocytes to blood vessel walls. They move out of the central axial column of laminar blood flow between capillaries and post capillary venules.
Blood stasis on inflammation caused by increased intravenous pressure and flow helps margination.
Leukocytes 'tumble' along endothelial surface and undergo weak and transient adhesion.
Leukocyte and endothelial molecules adhere- see slide 5.
Integrins on leukocyte surfaces interact with ligands on endothelial cell surfaces.
Induced by cytokines- they induce expression of endothelial receptors for neutrophils. (ICAM1)
Rolling stops when stable adhesion occurs.
Stable= several receptors binding.
Leukocyte passes from blood vessel endothelium to tissue via diapedesis (squeezes between endothelial cells at cell junctions).
Driven by chemokines (PECAM1)
Leukocyte moves from tissue to site of infection down a chemical gradient.
Exogenous and endogenous substances can be chemotactic. eg. Bacterial products, cytokines, complement components (C5a), lipoxygenase pathway of arachidonic acid metabolism products.
Chemotactic agents bind specific cell surface receptors: INCREASED CYTOSOLIC Ca2+
ASSEMBLY OF CYTOSKELETAL CONTRACTILE ELEMENTS
PSEUDOPODIA FORMATION -> MOTILE LEUKOCYTE.
-Stimuli for activation- Microbial substances
Products of necrotic cells
-These are sensed by various cell surface receptors- Toll like receptors
7-transmembrane G protein receptor family.
-Results in ENHANCED FUNCTION.
-> Production of lysosomal enzymes and ROS/RNS.
-> Production of mediators to amplify inflammatory response.
Undertaken by macrophages and neutrophils.
-Recognition and attachment of particle.
-Engulfment, formation of phagocytic vacuole.
-Killing and degradation of ingested material.
Uses specific cell surface receptors.
Opsonins enhance phagocytosis- IgG, complement C3, lectins.
Microbial substances produced in lysosome.
Phagocytosis stimulates oxidative burst.
ROS free radicals produced.
Phagocytosed particles are degraded by lysosomal acid hydrolases.
Phagocyte oxidase is only activated on phagolysosome fusion.
Prolonged inflammation (weeks)
May follow acute inflammation.
Can be an insidious low grade 'smouldering' response (eg. Johne's)
Caused by- persistent infection by certain organisms
- prolonged exposure to toxic agents
MORPHOLOGICAL FEATURES OF CHRONIC INFLAMMATION
Infiltration with mononuclear cells.
(EOSINOPHILS, MAST CELLS)
Attempts at healing by connective tissue replacement of damaged tissue- proliferation of small blood vessels and fibrosis.
When in the blood, are called MONOCYTES.
Adhere to vessel endothelium and leave the blood vessels via diapedesis, in response to infectious agent.
In the tissue- MACROPHAGE.
Macrophages are activated by action of activated T cells, which produce cytokines (particularly IFNy).
Activation can also be non immunogenic eg. action of endotoxin, fibronectin, chemical mediators.
ACTIVATED MACROPHAGES then either cause tissue injury or fibrosis.
ACTIVATED MACROPHAGES- TISSUE INJURY
Caused due to prolonged inflammation due to activated macrophage products.
-Toxic oxygen metabolites
-Neutrophil chemotactic factors
-Arachidonic acid metabolites
ACTIVATED MACROPHAGES- FIBROSIS
-Growth factors (Platelet Derived Growth Factor, Fibroblast Growth Factor, Transforming Growth Factor B)
WHAT ACTION DO ACTIVATED MACROPHAGES HAVE ON T LYMPHOCYTES?
Activated macrophages activate T lymphocytes by action of cytokines (eg. IL-12) and by ANTIGEN PRESENTATION to the T lymphocytes.
They also produce TNF, IL-1 and other inflammatory mediators to cause inflammation.
Activated T lymphocytes then produce IFNy to activate more tissue macrophages.
They also produce TNF and other inflammatory mediators to cause inflammation.
Epithelioid macrophages are modified macrophages, forming cohesive sheets.
Multinucleate giant cells- macrophages with fused nuclei.
LANGHAN'S TYPE GIANT CELLS- nuclei form ring round periphery of cell.
eg. Johne's disease in cattle and sheep.
Granulomatous lymphadenitis, thickened rugal folds in gut, histologically see MN giant cells, lymphocytes, intracellular bacteria (M. avium subspecies paratuberculosis)