Chapter 3

Question 1

Exudate vs transudate

Answer 1

Exudate = extravascular fluid with high protein content and cellular debris (pus = inflammatory exudate)

Transudate = extravascular fluid with low protein content, little cellular material, and low specific gravity (occurs without increase in vascular permeability such as in liver disease, renal disease, etc.) — instead d/t osmotic or hydrostatic pressure imbalance across vessel wall

Question 2

Describe integrin interaction between neutrophils and endothelium

Answer 2

LFA-1 found on neutrophils — binds ICAM1 and ICAM2 on endothelium

[MAC-1 on monocytes binds ICAM1 and 2 on endothelium; VLA-4 on monocytes/T cells binds VCAM-1 on endothelium; a4B7 on monocytes/Tcells binds MadCAM1 on GALT]

Question 3

Adhesion molecule present in intercellular junction between endothelial cells involved in migration of leukocytes

Answer 3

CD31

Question 4

Most common exogenous chemoattractant

Answer 4

Bacterial products (such as peptides possessing N-formylmethionine)

Question 5

Which component of complement acts as a chemotactic agent

Answer 5

C5a

Question 6

Which arachidonic metabolite participates in chemotaxis of leukocytes?

Answer 6

Leukotriene B4 (LTB4)

Question 7

Differentiate mannose vs scavenger receptors

Answer 7

Both are phagocytic receptors

Mannose receptor = lectin that binds terminal mannose and fucose residues on microbes

Scavenger receptors = bind modified LDL particles and more

Question 8

Describe role of ROS in intracellular destruction of microbes/debris

Answer 8

NADPH oxidized by NADPH oxidase (within lysosome and phagolysosome) while reducing O2*- to H2O2

H2O2 then converted by MPO to OCl2 which destroys microbes via halogenation or lipid peroxidation

Question 9

Discuss role of NO in intracellular destruction of microbes/debris

Answer 9

NO produced from Arg by iNOS

NO reacts with O2*- to generate ONOO- (peroxynitrite) which kills microbes

Question 10

Extracellular fibrillar networks of nuclear chromatin that provide a high concentration of antimicrobial substances at sites of infection and prevent spread of microbes by trapping them in the fibrils

Answer 10

NETs = neutrophil extracellular traps

[nuclear chromatin indicates nucleus is lost and neutrophil dies]

Question 11

Source and action of histamine

Answer 11

Source: stored as preformed molecules in mast cells, basophils, platelets

Action: vasodilation, increased vascular permeability, endothelial activation

Question 12

Cellular sources of prostaglandins

Answer 12

Mast cells

Leukocytes

Question 13

Physiologic actions of prostacyclin, PGE2 and PGD2, and thromboxane A2

Answer 13

Prostacyclin = vasodilation, inhibits platelet aggregation

PGE2 and PGD2 = vasodilation, increased vascular permeability

Thromboxane A2 = vasoconstriction, promotes platelet aggregation

Question 14

Physiologic actions of leukotrienes LTC4, LTD4, LTE4

[note cysteine-containing leukotrienes in particular]

Answer 14

Bronchospasm, increased vascular permeability

[can be inhibited by leukotriene receptor antagonists — useful in tx of asthma]

Question 15

Principle cellular sources and actions of TNF

Answer 15

Source: macrophages, mast cells, T cells

Stimulates expression of endothelial adhesion molecules and secretion of other cytokines, systemic effects

Question 16

Principle cellular sources and actions of IL-1

Answer 16

Source: macrophages, endothelial cells

Similar to TNF, greater role in fever

Question 17

Principle cellular sources and actions of IL-6

Answer 17

Source: macrophages

Systemic effects = acute phase response

Question 18

Principle cellular sources and actions of IL-17

Answer 18

Source: T cells

Recruitment of neutrophils and monocytes

Question 19

Principle cellular sources and actions of IL-12

Answer 19

Source: DCs, macrophages

Increased production of IFN gamma

Question 20

Principle cellular sources and actions of IFN-gamma

Answer 20

Source: T cells, NK cells

Activation of macrophages — increased ability to kill microbes and tumor cells

Question 21

3 complement pathways and what activates them

Answer 21

Classical = fixation of C1 to IgM or IgG which has combined with Ag

Alternative = microbial surface molecules like LPS

Lectin = MBL binds carbs on microbes and directly activates C1

Question 22

Which complement proteins are considered anaphylotoxins which stimulate histamine release?

Answer 22

C3a, C5a, C4a

Question 23

Which complement protein acts as an opsonin to promote phagocytosis by macrophages and neutrophils?

Answer 23

C3b

Question 24

C1 inhibitor blocks activation of C1 in the complement system. An inherited deficiency in this inhibitor results in what condition?

Answer 24

Hereditary angioedema

Question 25

What regulatory protein inhibits formation of C3 convertases?

Answer 25

Decay accelerating factor (DAF) [defects —> paroxysmal nocturnal hemoglobinuria]

Question 26

Morphologic types of acute inflammation

Answer 26

Serous (blisters, effusions in heart failure) Fibrinous (fibrin in pericardium) Purulent (staph, abscesses in pneumonia) Ulcers

Question 27

What do eosinophils contain that is toxic to parasites and human cells?

Answer 27

MBP

Question 28

Cytokines that promote M2 activation

Answer 28

IL-4, IL-13

Question 29

2 types of granulomatous inflammation

Answer 29

Foreign body granuloma Immune granuloma

Question 30

Morphologic features of granuloma

Answer 30

Epithelioid cells Multinucleated giant cells Central zone of necrosis

Question 31

Examples of diseases with granulomas

Answer 31

``` Tuberculosis Leprosy Syphilis Cat-scratch disease Sarcoidosis Crohn disease ```

Question 32

Acute phase reactant that binds microbial cell walls, may act as opsonin and fix complement, bind chromatin, possibly aiding in clearing necrotic cell nuclei

Answer 32

CRP [note elevated serum CRP may be risk factor in those with CAD]

Question 33

APP that binds red cells and causes them to form stacks that sediment more rapidly (basis for ESR lab)

Answer 33

Fibrinogen

Question 34

APP that has similar actions to CRP and prolonged production is a risk for secondary amyloidosis

Answer 34

Serum amyloid

Question 35

Chronically elevated levels of APP hepcidin puts the pt at risk for what condition?

Answer 35

Anemia

Question 36

Major cytokine involved in fibrosis

Answer 36

TGF-b

Question 37

Cells/molecules involved in acute and chronic asthma

Answer 37

Eosinophils | IgE Abs

Question 38

Cells/molecules involved in chronic athersclerosis

Answer 38

Macrophages | Lymphocytes

Question 39

_______ = inflamed LNs often d/t hyperplasia of lymphoid follicles and increased immune cells within

Answer 39

Lymphadenitis (aka lymphadenopathy)

Question 40

______ = inflammation of lymph vessels indicated by red streaks around a wound

Answer 40

Lymphangitis

Question 41

What enzyme protects us from lysosomal enzyme damage to our own cells?

Answer 41

Alpha-1 antitrypsin

Question 42

Things that prevent clot propagation

Answer 42

Nitric oxide PGI2 ADP-phosphatase [ADP is biggest platelet activator]

Question 43

Function of lipoxin A4/B4 (LXA/B4)?

Answer 43

Inhibition of inflammation by inhibiting neutrophil chemotaxis and adhesion to endothelium

Question 44

Histologically, _______ tissue appears pink, soft and granular that is characterized by proliferation of fibroblasts and new thin-walled delicate capillaries in a loose extracellular matrix

Answer 44

Granulation

Question 45

______ = growth factor for angiogenesis that recruits smooth muscle cells _____ suppresses endothelial proliferation and migration, and enhances the production of ECM proteins

Answer 45

PDGF TGF-B

Question 46

During scar formation, _____ are activated to remodel the deposited ECM; they are then shut down by _______ _______ are enzymes that are anchored to the PM and cleave and release EC domains of cell-associated cytokines and GFs like TNF, TGF-b, and EGF

Answer 46

MMPs; TIMPs ADAMs (A disintegrin and metalloproteinases)