Acute Inflammation 2

Question 1

Describe what the vascular response results in.

Answer 1

1. Exudation of fluid & plasma protein
2. Emigration of leukocytes

Question 2

Describe what the acute cell response results in.

Answer 2

-accumulation of inflam cells at site of injury
-phagocytosis

Question 3

Describe the different cells involved in acute inflammation.

Answer 3

1. Mast cells = found around blood vessels & early responder to injury
2. Endothelial cells = inflam & coagulation
3. Granulocytes = short lived, host defense
   >neutrophils, basophils, eosinophils
4. Monocytes/macrophages

Question 4

Describe neutrophils.

Answer 4

-made in BM -> blood
-inflam -> tissue via selectin (rolling), integrins (adhere), & chemotaxis
-die in 1-3d (short lived) = ‘kamikaze’
-phagocytose & destroy bacteria via granules
-primary/azurophilic = myeloperoxidase, hydrolase, defensins, lysozyme
-2ndary/specific = lactoferrin (chelates Fe), collagenase
-heterophils = granules stain eosinophilic (rabbits, birds, etc) * [no myeloperoxidase = caseous not liquid]
-surface receptors:
>Fc: antibody receptor & CR1/CR3: complement receptors = opsonins
>adhesion molecules: integrins/selectins

Question 5

Describe reactive oxygen species.

Answer 5

-released from neutrophils & macrophages into phagolysosome
-damage to cell membrane, protein, DNA
-gen thru respiration & stress like UV
-anti oxidant pathways protective

Question 6

Describe eosinophils.

Answer 6

-similar origin & fate of neutrophils
-BM production stim by IL5/GM-CSF *
-survive in tissue for weeks
-function: allergy & parasites
-attracted by eosinophilic chemotatic factor (mast cells), IgE, histamine *
-activated by IL5, IL3, Th2

Question 7

Describe monocytes.

Answer 7

-monocytes in circ
-change into macrophage in tissue *
-resting macrophage: kuppfer, alveolar, type A synoviocytes, microglial cells
-APC: skin, LN
-live longer than neutrophils
-phagocytic
-arrive after neutrophils
-role in chronic inflammation

Question 8

Describe monocyte functions.

Answer 8

-complement/ab receptors, TLR, integrins
-phagocytosis, gen NO *
-make IL1/6, TNFa -> liver
>sick: fever, loss of appetite, depress
>acute phase protein, clotting/complement factor *
-MHCII receptors: adaptive IR *
-central cell of chronic inflam *
-recovery from inflam *

Question 9

Describe mast cells.

Answer 9

-around blood vessels of CT of skin & mucous membrane
>initiate acute inflam *
>allergic/Type 1 HS reaction (IgE) *
>defense against parasites *
-long lived
-granules release: histamine, TNF, GF, substance P (pain) degranulation

Question 10

Describe basophils.

Answer 10

-BM prod by IL3
-tissue emigration by IL1, TNF
-survive for 2wk
-activated by IL1, IgE -> degranulation
>promote hypersensitive reactions
>attract eosinophils
-low # in blood
-similar func to mast cells*

Question 11

Describe the chemical response summary.

Answer 11

Question 12

Describe cell derived preformed vasoactive amines.

Answer 12

1. Histamine
   -mast cells, basophils, platelets
   >mast cell = initiate acute inflam resp
   -inc mucus prod & bronchial constriction
   -vasodilation & inc vascular permeability
2. Serotonin
   -platelets
   -imp neurotransmitter
   -vasodilation & inc vascular permeability
   *red, heat, swell

Question 13

Describe cell derived newly synthesized arachidonic acid metabolites.

Answer 13

-damage to cell membrane -> activation of phospholipase A2 that acts on cell membrane -> releasing arachidonic acid
-2 enzymes that act on the arachidonic acid to make metabolites:
1. Cyclooxygenase (Cox 1 & 2)
-prostaglandins & prostacyclins
-COX1 in gut & kidney
2. Lipoxygenase
-leukotrienes (LTs) & lipoxins

Question 14

Describe cytokines & chemokines.

Answer 14

1. Cytokines
   -proteins made by many cell types
   -inflam + other func
2. Chemokines
   -small protein cytokines that act as chemoattractants
   -bind to 7 trans membrane GPCR
   -secreted by activated macrophages, endothelial cells, and other cells
   -stim leukocyte recruitment in inflam & control migration of cells in tissues
   -production induced by microbes & other cytokines (IL1 & TNF)

Question 15

Describe inflammatory cytokines: IL1 & TNFa.

Answer 15

-secretion stim by physical injury, endotoxin, immune complex, toxins
-Autocrine, paracrine, endocrine
-actions on endothelium, leukocytes, fibroblasts, acute phase proteins
-‘acute phase resp’

Question 16

Describe the acute phase response.

Answer 16

-systemic early defense system activated by trauma, inf, stress, neoplasia, inflam
-tissue injury -> local inflam cells secrete cytokines into blood like IL1, IL6, TNFa
-liver -> makes lg # of acute phase reactants: C reactive protein, complement factors, mannose binding protein, ferritin
-goal: prevent inf, clear pathogen, initiate inflam process, contribute to healing

Question 17

Describe the acute phase response CS.

Answer 17

-fever
-inc sleep
-pain
-neutrophilia
-dec appetite (TNF inc lipid & protein mobilization)
>prolonged TNF -> cachexia (weight loss - cancer & inf)
-corticotropin & corticosteroid released
-severe = hypotension, dec vascular resistance, inc HR, dec blood pH -> SHOCK

Question 18

Describe the complement system.

Answer 18

-innate IS
-inflam activates circ complement proteins
-activation stim by Ab, microbes, endotoxins, venom *
-Ab & phagocytic cells to remove pathogens
-made by liver (20+ proteins & products in plasma)
>proteins #’d C1-C9
-activation = inc vascular permeability, chemotaxis, oponisation
>activation by Ag+Ab complex or contact w microbial surface molecules

Question 19

Describe the clotting system.

Answer 19

-clotting + inflam
-2 pathways:
1. Activation of thrombin
2. Formation of fibrin

Question 20

Describe the clotting cascade.

Answer 20

1. Plasma derived (intrinsic)
   -hageman factor (F12) activated secondary to exposure of collagen & BM when endothelium is damaged
2. Tissue derived (extrinsic)
   -tissue factor released when sub endothelial damage
   -fibrin = pink
   -framework for repair

Question 21

Describe the summary of acute inflammation.

Answer 21

Question 22

Describe leukocyte induced tissue damage.

Answer 22

-neutrophils & macrophages release:
>lysosomal enzymes
>ROS
>arachidonic acid metabolism
—prostaglandins, leukotrienes into extravascular space
-endothelial & tissue damage = amplifying effects of initial injury
-leukocyte becomes bad guy if unchecked

Question 23

Describe the resolution of inflammation.

Answer 23

Question 24

Describe the outcomes of acute inflammation.

Answer 24