Acute Inflammation

Question 1

What is acute inflammation?

Answer 1

the reaction of vascularizezed tissue to injury

Question 2

acute inflammation involves the interaction of ___

Answer 2

• pathogen/injury
• host inflammatory cells
• complement and coagulation cascades
• chemokines and cytokines

Question 3

acute inflammation involves the accumulation of

Answer 3

fluid, plasma proteins, and innate immune cells

Question 4

the intensity of the response of AI is determined by

Answer 4

the stimulus, the duration of the stimulus, genetics of the host local factors, and medical interventions

Question 5

causes of inflammation

Answer 5

infections, tissue necrosis(ischemia, thermal injury, etc), foreign bodies, and immune reactions (hypersensitivity)

Question 6

inlfammasome

Answer 6

• multi-protien complex characterized by activation of CASPASE 1
• it cleaves IL-1 to its active form to set the inflammatory cytokines in action

Question 7

what activates monocytes?

Answer 7

pamp and damps (pathogen and damage assoc molecular pathogens)

Question 8

inflammatory cytokines that recruit neutrophils

Answer 8

IF-1 and TNFa

Question 9

cellular response of GPCRs in AI

Answer 9

cytoskeletal changes and signal transduction which causes:

• increased integrin avidity causing adhesion to endothelium
• chemotaxis and migration into tissues

Question 10

Cellular response of Toll-like receptors

Answer 10

• production of mediators which amplify the inflammatory reaction
• production of reactive oxygen species and lysosomal enzymes

Question 11

cellular response of cytokine receptors

Answer 11

production of reactive oxygen species and lysosomal enzymes

Question 12

cellular response of phagocytic receptor

Answer 12

• phagocytosis of microbe into phagosome

- production of reactive oxygen species and lysosomal enzymes

Question 13

vascular response to AI

Answer 13

• NO causes vasodilation to increase flow and vascular permeability
• cytokine/chemokine induced endothelial changes allow innate cells access to the inflammatory site
• plasma proteins like complement and Ab access the extracellular space
• BASIC GOAL: increase the chance that a leukocyte can respond to the signal

Question 14

5 main signs of inflamation

Answer 14

• rubor (redness)
• calor (heat)
• dolor (pain)
• tumor (swelling/edema from incr vascularization)
• loss of function

Question 15

Phase 1 of AI

Answer 15

• recognition of injury and attraction of neutrophils
• expression of surface lectins and proteoglycans cause leukocytes to stick to epithelium and roll onto different receptors. Then the WBCs enter the tissue (diapedesis) and migrate to the source of the injury

Question 16

which cytokines increase adhesion molecules?

Answer 16

IL-1, IL-6, and TNFa

Question 17

what is chemotaxis

Answer 17

unidirectional movement along a chemical gradient which could be:

• bacterial peptides
• complement components (especial C5a)
• proinflammatory cytokine tetrad

Question 18

how does chemotaxis work?

Answer 18

the chemoattractants activae membrane receptors on the innate cells that then activate cytoskeleton (especially actin) changes that move the cell along the gradient to the site of the inflammatory stimulus

Question 19

Phase 2 of AI

Answer 19

• recruitment of monocytes/macrophages, dendritic cells, and T cells especially by neutrophil degranulation
• this also signals more neutrophils to stop coming

Question 20

smoking inhibits ____ in AI

Answer 20

the neutrophil turn off signal

Question 21

location of monocyte

Answer 21

blood

Question 22

location of macrophage

Answer 22

fluids in the body

Question 23

location of histiocyte

Answer 23

tissue

Question 24

which cytokines cause proliferation of WBCs in AI?

Answer 24

G-CSF, GM-CSF, and IL-3

Question 25

Which cytokines cause maturation of WBCs in AI?

Answer 25

IL-1, IL-6, and IL-8

Question 26

sequence of cell traffic in AI

Answer 26

edema--neutrophils---monocytes/macrophages

Question 27

neutrophils (or PMNs)

Answer 27

- most numerous leukocyte in circulation - signature cell of AI - marrow capable of rapid production and release - segmented nuclei - granules which kill the offender

Question 28

Bone marrow response to AI

Answer 28

- cytokines and growth factors signal the marrow to make more cells - it responds by pushing mature and slightly immature but functional neutrophils out early and in vast amounts - causes elevated leukocyte count in pts

Question 29

left shift in AI

Answer 29

- bone marrow is producing immature neutrophils (cells to the left of mature) called bands - bands will show up in the pts peripheral blood

Question 30

actions of neutrophils at site of injury

Answer 30

- phagocytosis - recognition/attachment - engulfment/degranulation to form the phagolysosome - killing/degradation via an oxidative burst that generates kililng molecules - NETS (neutrophil extracellular traps)

Question 31

recognition and attachment of neutrophils in AI

Answer 31

Ab and C3b coating bind the pathogen to FcR and C3bR

Question 32

NETs

Answer 32

- chromatin spray to the outside of the cell to trap bacteria and fungi - its chromatin is laden with killer granules - causes neutrophil to die b/c it sacrifices its nucleus

Question 33

oxidative burst and killing

Answer 33

- degranulation - oxidative burst - activation of NADPH generated H2O2 - lysosomal enzymes donate MPO - MPO + halide =HOCl * *important- need NADPH

Question 34

monocytes/macrophages

Answer 34

- largest leukocyte in the blood - has many granules, large golgi, and indented nucleus - some home to specific organs and take up residence as fixed macrophages

Question 35

phase 4 of AI

Answer 35

- cleanup of debris - main players in cleanup = TGF-B and IL-10 - scavenging of apoptotic neutrophils promotes macrophage growth factors and repair

Question 36

control of AI is highly dependent on _____

Answer 36

macrophages

Question 37

No TLR or phagocytic receptor activation after AI leads to ___

Answer 37

- decreased pro-inflammatory mediator syntheis and release, which macrophages sense as they are cleaning up dying neutrophils - predominant cytokines are TGF-B and IL-10

Question 38

Serous/Transudate AI

Answer 38

- least severe - protein poor transudate from capillary to a space- peritoneal, pericardial, or pleural - cells aren't leaky, so only lose fluid and not protein

Question 39

Fibrinous AI

Answer 39

- intermediate severity | - fluid with larger molecules dominated by fibrinogen which converts to fibrin and potential scarring

Question 40

Suppurative/Abscess/Exudate AI

Answer 40

- most severe - protein rich fluid with inflammatory cells and alive and dead necrotic debris - high hydrostatic pressure and leaky endothelial cells so protein leaks along with fluid

Question 41

ulcerative AI

Answer 41

underlying inflammation causes excavation of a mucosal or skin surface