Cellular response in inflammatory response
Movement of luekocytes to the site of injury
Nb: blood demonstrates laminar flor and WBCs are usually in the central column
5 steps of movement of leukocytes to injury
Margination: blood stasis helps WBCs fall towards edges of lumen
Rolling: bouncing/creeping along
Adhesion: connection between endothelial lining and WBC becomes much stronger
Transmigration: squeezing through of WBC
Chemotaxis: migration from endothelial cell wall to site of injury
Cytokines are messengers telling endothelial cells to express receptors to which WBCs can adhere.
movement of leukocytes to blood vessel walls
Laminar flow of blood between capillaries and post-capillary venules.
leukocytes move out of central axial column of blood
enhanced by blood stasis suring inflammation
leukocytes tumble along endothelial surface and undergo weak and transient adhesion
Endothelial molecule: P-selectin and E-selectin
Leukocyte molecule: sialyl-lewis x-modified proteins
Endothelial and leukocyte molecule: glycam1 (CD34) and L-selectin.
mediated by integrins on leukocyte surfaces
interact with ligands on endothelial surfaces
induced by chemokines (IL-1, IL-6, TNF, PDGF, PAF)
Endothelial molecules: ICAM-1 (intracellular adhesion molecule; VCAM-2 (vascular cell adhesion molecule); and E-selectin
Leukocyte molecule: CD11/CD18 integrins; VLA-4 integrin; silalyl-lewis x-modified proteins
leukocytes squeeze between endothelial cells at intracellular junctions--DIAPEDESIS
driven by chemokines
Endothelial molecule: ICAM-1; PECAM-1 (platelet endothelial cell adhesion molecule)
Leukocyte molecule: CD11/CD18 integrins; PECAM-1
leukocytes migrate along a chemical gradient towards site of injury
Both exogenous and endogenous susbstances can be chemotactic
-bacterial products, CKs, components of complement cascade, products of lipoxygenase pathway of arachidonic acid metabolism
These products/substances will also bind specific cell receptors: increase cytosolic calcium, assembly of cytoskeletal contractile elements; pseudopodia formation- enhances ability of leukocyte to move.
occurs upon arrival to site of injury
Stimuli for activation: microbial substances, products of necrotic cells
Sensed by various cell surface receptors (toll-like receptos, and 7-transmembrane G protein receptor family)
Result: enhanced function--> phagocytosis, production of lysosomal enzymes and reactive oxygen and nitrogen species; production of mediators to amplify inflammatory reaction
Phagocytosis: macrophages and neutrophils
recognition and attachment of particle
engulfment and formation of phagocytic vacuole
killing and degradation of ingested material: use specific cell- surface receptors; opsonins (attract phagocytes): IgG, complement C3 and lectins
Intracellular killing and degradation
production of microbicidal substances in the lysosome- protects cell from itself by keeping it in packets
phagocytosis stimulates oxidative burst
production of ROS free radicals
particles are degraded by lysosomal acid hydrolases
phagocyte oxidase activated only when phagosome and lysosome fuse- helps corner off microbicidal activity.
prolonged inflamm (weeks)
may follow acute inflammation
can be an insidious, low grade or "smoldering" response
Causes: persistent infeciton by certain organisms, prolonged exposure to toxic agents, autoimmunity.
Morphological features: infiltration with mononuclear cells, tissue destruction, attempts at healing by connective tissue replacement of damaged tissue by proliferation of small blood vessels and fibrosis
Cells of chronic inflamm: macs, lymphocytes, plasma cells, eosinophils, mast cells
Activated macs can damage tissue if uncontrolled, also responsible for fibrosis.
monocyte has vacuolated cytoplasm in edta, rounded nucleus in tissues with much more cytoplasm.
Interactions between macs and lymphocytes- what can activated macs do?
1) support inflammation with stimulation of inflammatory mediators (i.e. IL-1 and TNF) which stimulate neutrophils
2) can present antigen to T-cells
3) can stimulate cytokine (IL-2) to go to T-cells
Activated T-cell can also stimulate TNF and other inflammatory mediators. Also can stimulate IFN-gamma to stimulate macrophage production.
mycoplasma adhere to ciliated epithelium
bifurcations of bronchi and bronchioles
hyperplasia of lymphocytes and plasma cells (typical chronic inflammation response)-->formation of lymphoid follicles.
epithelioid macrophages: modified macrophages that form cohesive sheets
multinucleate giant cells: Langhan's type giant cells--> nuclei form ring around periphery. if macrophages can't get rid of injurious agent, get formation of multinucleate giant cells.
acid fast intracellular bacilli
organisms usually abundant in cattle, sparse in sheep-- cause inflamed rugae of GI tract. can be pigmented in sheep
cutaenous actinobacillosis- caused by actinobacillus lignieresii
Pyogranulomatous inflammation--> neutrophils, macrophages, epithelioid macrophages, langhan's giant cells, lymphocytes, plasma cells
Splendore-Hoeppi material: "club" (suit of card club) shaped colonies-- sulphur granules; precipitated material around bacterial colonies