Inflammation and the Cellular response

Question 1

Cellular response in inflammatory response

Answer 1

Movement of luekocytes to the site of injury

Nb: blood demonstrates laminar flor and WBCs are usually in the central column

Question 2

5 steps of movement of leukocytes to injury

Answer 2

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.

Question 3

Margination

Answer 3

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

Question 4

Rolling

Answer 4

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.

Question 5

Adhesion

Answer 5

between receptors

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

Question 6

Transmigration

Answer 6

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

Question 7

Chemotaxis

Answer 7

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.

Question 8

Leukocyte activation

Answer 8

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

Question 9

Phagocytosis: macrophages and neutrophils

Answer 9

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

Question 10

Intracellular killing and degradation

Answer 10

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.

Question 11

Chronic inflammation

Answer 11

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.

Question 12

Monocyte/macrophage appearance

Answer 12

monocyte has vacuolated cytoplasm in edta, rounded nucleus in tissues with much more cytoplasm.

Question 13

Interactions between macs and lymphocytes- what can activated macs do?

Answer 13

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.

Question 14

Mycoplasmal pneumonia

Answer 14

mycoplasma adhere to ciliated epithelium

BALT

bifurcations of bronchi and bronchioles

hyperplasia of lymphocytes and plasma cells (typical chronic inflammation response)–>formation of lymphoid follicles.

Question 15

Granulomatous inflammation

Answer 15

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.

Question 16

Johne’s disease

Answer 16

mycobacterium paratuberuclosis

acid fast intracellular bacilli

organisms usually abundant in cattle, sparse in sheep– cause inflamed rugae of GI tract. can be pigmented in sheep

Question 17

Pyogranulomatous inflammation

Answer 17

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

Fibrosis

Abscessation