inflammation

Question 1

inflammation definition

Answer 1

response to infection or tissue necrosis that allows inflammatory cells, plasma proteins, and fluid to enter the interstitial space with the goal of eliminating the pathogen/clearing debris

Question 2

features of inflammation

Answer 2

rubor, calor, dolor, tumor, decreased function

Question 3

steps of inflammation

Answer 3

1. recognition of injurious agent
2. recruitment of WBCs
3. removal of agent
4. regulation of response
5. repair

Question 4

characteristics of acute inflammation

Answer 4

• innate immunity
• immediate response
• pyogenic
• neutrophils, antibodies, complement
• associated with extracellular organisms

Question 5

characteristics of chronic inflammation

Answer 5

• adaptive immunity
• delayed response
• more specific
• lymphocytes, plasma cells, monocytes/macrophages
• associated with intracellular organisms

Question 6

pro-inflammatory cytokines

Answer 6

IL1 and IL6 => fever
IL8 => attracts neutrophils
TNFa => increased cyclooxygenase

Question 7

pro-inflammatory mediators (endothelial cell contraction)

Answer 7

prostaglandins, leukotrienes, bradykinins, histamines

Question 8

prostaglandins

Answer 8

arachidonic acid products that mediate vasodilation and increased vascular permeability, pain, and fever

Question 9

leukotrienes

Answer 9

arachidonic acid products that attract neutrophils, mediate bronchospasm, and increased vascular permeability

Question 10

bradykinins (from kallikrein)

Answer 10

mediate vasodilation via NO, increased vascular permeability, and pain

Question 11

histamines

Answer 11

mediate vasodilation, endothelial cell contraction, and increased vascular permeability

Question 12

what is the function of the vascular component of inflammation?

Answer 12

vasodilation (for increased blood flow) and increased vascular permeability (via endothelial cell contraction and damage)

Question 13

what are the cellular components of acute inflammation?

Answer 13

neutrophils:

• drawn towards inflammatory mediators from mast cells and macrophages
• phagocytose and destroy organisms
• release cytokines to draw more neutrophils

monocytes:
- release more cytokines

Question 14

what are the cellular components of chronic inflammation?

Answer 14

if neutrophils can’t remove the organisms, they produce cytokines to draw:

• lymphocytes
• plasma cells
• monocytes and macrophages

Question 15

steps of neutrophil recruitment in the blood vessel

Answer 15

1. margination
2. rolling
3. adhesion
4. transmigration and chemotaxis

Question 16

neutrophil margination

Answer 16

vasodilation and increased vascular permeability => slow blood flow => white cells move to periphery of vessel

Question 17

neutrophil rolling

Answer 17

1. histamine, IL1, and TNFa => P-selectin and E-selectin expression on endothelial cells
2. sialyl lewis X on neutrophils binds to P-selectin and E-selectin
3. selectin-neutrophil binding causes slow rolling of neutrophil on vessel wall

Question 18

neutrophil adhesion

Answer 18

1. C5a and leukotrienes => integrin expression on neutrophils
2. TNFa and IK1 => ICAM and VCAM (cellular adhesion molecules) on the endothelium
3. integrin - ICAM/VCAM interaction causes adhesion of neutrophil to endothelium

Question 19

neutrophil transmigration

Answer 19

neutrophils migrate through the endothelium via diapedesis and move towards chemokines (IL8 and C5a) via chemotaxis

Question 20

what is the cause and presentation of leukocyte adhesion deficiency (LAD)?

Answer 20

caused by: defect in integrins (CD18 subunit)

causes: delayed separation of umbilical cord, recurrent bacterial infections, high neutrophil counts in blood (they can’t escape to tissues)

Question 21

what are the stages of phagocytosis?

Answer 21

1. recognition and attachment
2. engulfment
3. destruction

Question 22

what receptors are involved in recognition?

Answer 22

• PRRs for PAMPs: TLRs, NOD, RIG-I, MBL

- receptors for opsonins: complement C3b, IgM, IgG

Question 23

how does a neutrophil engulf a bacterium?

Answer 23

1. C3b (opsonin) binds to bacterial capsule
2. Binds to C3b receptors on a neutrophil
3. Neutrophil invaginates membrane to form phagosome

Question 24

how do neutrophils destroy phagocytosed bacteria?

Answer 24

phagosome fuses with lysosome (which contains killing enzymes), forming a phagolysosome

Question 25

what enzymes are involved in oxygen dependent killing of organisms?

Answer 25

Respiratory burst: 1. NADPH oxidase forms superoxidase radical 2. superoxide dismutase forms hydrogen peroxide 3. myeloperoxidase catalyzes production of hypochlorite (in neutrophils only--most effective killer)

Question 26

how to catalase + organisms evade immunity?

Answer 26

bacterial catalase breaks down hydrogen peroxide, decreasing the formation of hypochlorite by myeloperoxidase

Question 27

what are the cause and presentation of chronic granulomatous disease?

Answer 27

cause: defect in NADPH oxidase => can't product hydrogen peroxide to kill bugs causes: recurrent infections from catalase + organisms and failure to kill organisms => granulomas

Question 28

what are the cause and presentation of chediak-higashi?

Answer 28

cause: genetic defect in vesicle formation and trafficking => can't form phagolysosome causes: neutropenia with giant granules (lysosomes with built up myeloperoxidase) in neutrophils and monocytes, oculocutaneous albinism, susceptibility to pyogenic infections

Question 29

how do inflammation/neutrophils damage tissues?

Answer 29

- neutrophils non-specifically release enzymes and free oxygen radicals into the extracellular space - if a pathogen is not cleared, neutrophils continue to be activated => lots of free oxygen radicals => DNA damage and potential dysplastic/neoplastic change

Question 30

how is inflammation resolved?

Answer 30

some tissues can regenerate (such as the top layer of the epithelim) 1. macrophages release anti-inflammatory molecules (TGFB) 2. macrophages recruit fibroblasts and release vascularization factors (forming granulation tissue) 3. if tissue architecture was lost: fibroblasts deposit collagen and ECM to form scars

Question 31

what are the components of granulation tissue?

Answer 31

fluid/empty space, blood vessels, collagen/fibroblasts

Question 32

what are the two pathways of wound healing and when is each used?

Answer 32

First intention/primary union: - wound only involves epithelium - wound edges are approximated Secondary intention/secondary union - tissue loss is extensive - would edges cannot be brought together

Question 33

what are the steps of healing by first intention?

Answer 33

1. hemorrhage and blood clot 2. acute inflammation and scab formation 3. proliferation: formation of epithelial cell layer under scab and granulation tissue below 4. organization: fibroblasts make collagen and inflammation decreases 5. scar formation: epidermis is intact but there is a loss of sweat glands and hair follicles and there is fibrous tissue beneath

Question 34

how is healing by secondary intention different?

Answer 34

- larger clot - more inflammation - more granulation tissue - wound contraction mediated by fibroblasts

Question 35

what is fibrosis?

Answer 35

parenchymal organ damage caused by excessive collagen/ECM deposition in response to injury => organ disfunction mediated by TGFB and occurs when tissue cannot regenerate