Acute inflammation

Question 1

Acute inflammation is characterized by the presence of what?

Answer 1

edema and neutrophils

Question 2

What type of response is AI?

Answer 2

Immediate with limited specificity (innate immunity)

Question 3

What are the major mediators of AI?

Answer 3

Toll-like receptors (TLRs), Arachadonic acid metabolites, Mast cells, Complement, and Hagemen factor (factor XII)

Question 4

Where do you find TLRs?

Answer 4

On cells of innate immunity (e.g., macrophages and dendritic cells)

Question 5

How are TLRs activated?

Answer 5

Pathogen-associated molecular patterns (PAMPs)

Question 6

CD 14 (TLR4 co-receptor) on macrophages recognizes…

Answer 6

Lipopolysaccaride (a PAMP) on outer membrane of gram-negative bacteria

Question 7

What happens upon TLR activation?

Answer 7

Upregulation of NF-kB (a nuclear transcription factor), which activates immune response genes that produce multiple immune mediaters

Question 8

Where can you find TLRs that help with chronic inflammation?

Answer 8

Cells of adaptive immunity (e.g., lymphocytes)

Question 9

What enzyme releases AA from phospholipid cell membrane?

Answer 9

Phospholipase A2

Question 10

What two enzymes act on AA? What do they produce?

Answer 10

Cyclooxygenase –> produces prostaglandins (PG) and

5-lipoxygenase –> produces leukotrienes (LT)

Question 11

What role do PGI2, PGD2, and PGE2 play in AI?

Answer 11

Mediate vasodilation (at arteriole level) and increased vascular permeability (at post-capillary venule)

Question 12

What else does PGE2 do with regards to AI?

Answer 12

Mediates pain and feeeeever

Question 13

LTB4 function?

Answer 13

Attracts and activates neutrophils

Question 14

LTC4, LTD4, and LTE4 function?

Answer 14

Mediate vasoconstriction, bronchospasm, and increased vascular permeability. (–>smooth muscle contraction)
They are slow reacting substances of anaphylaxis.

Question 15

What are the main activators of neutrophils?

Answer 15

LTB4, C5a, IL-8, and bacterial products

Question 16

Where are mast cells present?

Answer 16

Widely distributed throughout connective tissue

Question 17

How are mast cells activated?

Answer 17

(1) Tissue trauma, (2) complement proteins C3a and C5a, or (3) cross-linking of cell-surface IgE by antigen

Question 18

What is the immediate response of mast cells?

Answer 18

Release of preformed histamine granules. Mediates vasodilation or arterioles and increased vascular permeability.

Question 19

What is the delayed response of mast cells?

Answer 19

Production of AA metabolites, particularly leukotrienes. Allows for maintenance of acute inflammation.

Question 20

What are complement proteins?

Answer 20

Proinflammatory serum proteins that “complement” inflammation

Question 21

What are the three pathways of activation?

Answer 21

Classical, Alternative, and Mannose-binding lectin (MBL)

Question 22

How is the classical pathway activated?

Answer 22

C1 binds IgG or IgM that is bound to antigen

–> “GM makes CLASSIC cars”

Question 23

How is the alternate pathway activated?

Answer 23

Microbial products directly activate complement

Question 24

How is the MBL pathway activated?

Answer 24

MBL binds to mannose on microorganisms and activates complement

Question 25

Where is the earliest all common pathways meet?

Answer 25

Production of C3 convertase (mediates C3--> C3a and C3b) | --> produces C5 convertase (mediates C5--> C5a and C5b)

Question 26

How is the membrane attack complex (MAC) formed?

Answer 26

C5b complexes with C6-C9

Question 27

What are the roles of C3a and C5a?

Answer 27

Trigger mast cell degranulation (anaphylatoxins)--> histamine-mediated vasodilation and increased vascular permeability C5a also is chemotactic for neutrophils

Question 28

What is the role of C3b?

Answer 28

Opsonin for phagocytosis

Question 29

What does MAC do?

Answer 29

lyses microbes by creating a hole in the cell membrane

Question 30

What is Hageman factor (XII)?

Answer 30

Inactive proinflammatory protein produced in liver

Question 31

How is factor XII activated?

Answer 31

Exposure to subendothelial or tissue collagen

Question 32

What does an activated factor XII activate?

Answer 32

(1) Coagulation and fibrinolytic systems (mechanism by which DIC can occur) (2) Complement (3) Kinin system

Question 33

How does the kinin system work?

Answer 33

Kinin cleaves high-molecular-weight kininogen (HMWK) to bradykinin

Question 34

What does bradykinin do?

Answer 34

Mediates vasodilation and vascular permeability (like histamine), also mediates pain

Question 35

What are the Cardinal signs of inflammation?

Answer 35

Redness (rubor), warmth (calor), swelling (tumor), pain (dolor) and fever

Question 36

Why do you see redness and warmth?

Answer 36

Due to vasodilation --> increased blood flow | --> Occurs via relaxation of arteriolar smooth muscle

Question 37

What are the key mediators of relaxation of arteriolar smooth muscle in inflammation?

Answer 37

Histamine, prostaglandins, and bradykinin

Question 38

Why do you have swelling in inflammation?

Answer 38

Leakage of fluid from postcapillary venules into the interstitial space (exudate)

Question 39

What are the key mediators of swelling?

Answer 39

(1) Histamine - endothelial cell contraction | (2) tissue damage - endothelial cell disruption

Question 40

What are the key mediators of pain?

Answer 40

Bradykinin and PGE2 --> sensitize sensory nerve endings

Question 41

Why does fever occur in inflammation?

Answer 41

Pryogens (e.g., LPS from bacteria) cause macrophages to release IL-1 and TNF - -> increase COX activity in parivascular cells of hypothalamus - -> Increased PGE2 raises temperature set point