Inflammation 1 Flashcards
What can cause inflammation?
Injury (infection), trauma, foreign bodies, immune reactions and necrosis
What is the response to injury?
Vascular changes and cellular changes through chemical mediators and morphologic patterns
What are the vascular changes that occur?
Changes in flow and vessel caliber (vasodilation), which first involves arterioles then capillary beds
What mediates vascular changes?
Histamine and nitric oxide
What is the result of vascular changes?
Increased heat (calor) and redness/erythema (rubor)
What are the 5 types of cellular changes?
Stasis (inhibition of cell growth), white cell margination, rolling (leukocytes slow down and adhere to the wall), adhesions and migration
What is the normal flow of blood?
Central within a vessel. With dilation the rate of flow slows and cells are able to move peripherally (especially large white cells) - also white cell margination (migration towards vessel walls)
Why can cells stick to vessels in inflammation and not normally?
Normally the vessel walls are too slippy so blood cells can’t stick, however in inflammation the vessels express proteins on the lumens surface that match a protein on the white cell surface (lock and key - ligands)
What specific molecules are expressed on cell walls?
Selectins, integrins, vascular cell adhesion molecules (VCAM) and intercellular adhesion molecule (ICAM)
What do integrins bind to?
ICAM
Is integrin/selectin interaction with ligands low or high affinity?
Low affinity (binding on AND off is fast)
What increases selection expression?
Histamine and thrombin (from inflammatory cells)
What increases endothelial cell expression of VCAM and ICAM?
Tumour necrosis factor (TNF) and interleukin-1 (IL-1)
What do chemokines from the site of injury bind to?
Proteoglycans on the endothelial cell surface (which then increase the affinity of VCAMs and ICAMs for integrins
What are leaky vessels?
The loss of proteins from inside the cell to outside, which then causes water to follow = change in the cell’s osmotic balance (swelling)
Why do vessels leak?
Endothelial contraction, direct injury, white cells, transcyotisis and new vessel formation
What molecule makes new vessels but also increases leakiness?
Vascular endothelial growth factor (VEGF)
What is chemotaxis?
Cells follow a chemical gradient and move along it (involves bacterial components, complement, leukotrienes and cytokines (interleukins)
What are the 3 phases of phagocytosis?
Recognition/attachment, engulfment and killing/degradation
What are the recognition receptors in phagocytosis?
Mannose receptors, scavenger receptors and opsonins
Why are mannose receptors used in phagocytosis?
Bacterial surface glycoproteins and glycolipids contain (terminal) mannose residues but mammalian glycoproteins and glycolipids do not (they have silica acid or N-acetylgalactosamine)
Why are scavenger receptors used in phagocytosis?
Similar to mechanism that phagocytes recognise low density lipoproteins
Why are opsonins used in phagocytosis?
Bacteria are protein coated so they stand out from ‘self’ cells. These coats include components of the complement cascade as well as immunoglobulin (IgG)
What happens in engulfment in phagocytosis?
Pseudopods are formed (fake limbs) as are vesicles (phagosomes) that join with lysosomes (phagolysosomes)
What happens in killing and degradation in phagocytosis?
NAPDH oxidase helps oxygen to gain an electron from NAPDH to become superoxide. Nitric oxide synthase combines NO with superoxide to produce ONOO
What are the 4 pillars of inflammation?
Rubor, tumor, calor and dolor
What is rubor?
Redness caused by increased perfusion, slow blood flow and increased permeability of vessels
What is calor?
Heat caused by increased perfusion, slow blood flow and increased permeability of vessels
What is tumor?
Swelling due to vascular changes (eg more perfusion, slow flow and increased permeability)
What is dolor?
Pain mediated by prostaglandin and bradykinin
What is functiono laesa?
Loss of function (technically the 5th pillar of inflammation but not always included)
What inflammatory cell characterises acute inflammation?
Neutrophil (a polymorph/many lobes to the nucleus and granulocyte with phagocytic and cytotoxic abilities)
