Chapter 3: Acute Inflammation I

Question 1

Acute inflammation has 3 major components. What are they?

Answer 1

dilation of small vessels, increased permeability , emigration of leukocytes

Question 2

What is vasodilation induced by primarily?

Answer 2

histamine

Question 3

What is stasis?

Answer 3

the engorgement of small vessels with slowly moving red cells

Question 4

What is the source of histamine?

Answer 4

mast cells, basophils, and platelets

Question 5

What is the source of prostaglandins and leukotrienes?

Answer 5

mast cells and leukocytes

Question 6

What are two mechanisms that are responsible for the increased permeability of postcapillary venules?

Answer 6

contraction of endothelial cells and endothelial injury

Question 7

What elicits the contraction of the endothelial cells?

Answer 7

histamine, bradykinin, and leukotrienes

Question 8

What do the effects on the microvasculature (flow and permeability) direct affect?

Answer 8

the recruitment of leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent

Question 9

What do the presence of red streaks near a skin wound represent?

Answer 9

inflamed lymphatic channels and they are diagnostic of lymphangitis

Question 10

The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is mediated and controlled by what?

Answer 10

adhesion molecules and cytokines called chemokines

Question 11

The journey of leukocytes from the vessel lumen to the tissue is a process that can be divided into sequential phases. What are these phases?

Answer 11

1) In the lumen, margination, rolling, and adhesion to the endothelium 2) migration across the endothelium and vessel wall 3) migration in the tissues

Question 12

Two additional mediators act on the endothelial cells of postcapillary venules adjacent to the infection and induce the coordinated expression of numerous adhesion molecules. What are these mediators?

Answer 12

TNF and IL-1

Question 13

The attachment of leukocytes to endothelial cells is mediated by what?

Answer 13

adhesion molecules whose expression is enhanced by cytokines (which are secreted by sentinel cells in tissue in response to microbes)

Question 14

What are the two major families of proteins involved in leukocyte adhesion and migration?

Answer 14

selectins and integrins and their ligands

Question 15

What selectin is expressed on the leukocyte?

Answer 15

L-selectin

Question 16

What does binding of the selectins to their receptors cause?

Answer 16

rolling

Question 17

What is firm adhesion mediated by?

Answer 17

integrins

Question 18

What is the main integrin ligand on the endothelium?

Answer 18

VCAM-1 and ICAM-1

Question 19

In regards to integrins, what do leukocytes normally express? (no integrins, some integrins??)

Answer 19

leukocytes normally express integrins in a low affinity state

Question 20

What is the name of the process of migration of the leukocytes through intact endothelium?

Answer 20

transmigration or diapedesis

Question 21

Where does transmigration mostly occur?

Answer 21

in postcapillary venules

Question 22

Several adhesion molecules present in the intercellular junctions between endothelial cells are involved in the migration of leukocytes. These molecules include a member of the immunoglobulin family called what?

Answer 22

PECAM-1 (or CD31)

Question 23

After traversing the endothelium, leukocytes pierce the basement membrane how?

Answer 23

a collagenase

Question 24

After exiting the circulation, leukocytes move in the tissues toward the offending agents by a process called what?

Answer 24

chemotaxis along a chemical gradient

Question 25

What are the most common endogenous chemoattractants?

Answer 25

cytokines in the chemokine family (IL-8), Complement (C5a), and arachidonic acid (AA) metabolites (LTB4)

Question 26

Where do the chemotactic agents bind to?

Answer 26

specific seven transmembrane G protein coupled receptors on the surface of leukocytes

Question 27

What happens once the chemotatic agents bind to the seven transmembrane G protein coupled receptors?

Answer 27

there is a polymerization of actin and reorganization of the cytoskeleton allows the leading edge of the leukocyte to extend filopodia that pull the back of the cell in the direction of the extension

Question 28

In most forms of acute inflammation, what leukocyte predominates in the inflammatory infiltrate during the first 6-24 hours?

Answer 28

neutrophils

Question 29

what replaces the neutrophils in 24-48 hours?

Answer 29

macrophages/ monocytes

Question 30

Once leukocytes (primarily neutrophils and macrophages) have been recruited to a site of infection or cell death what must occur?

Answer 30

their functional properties must be activated so that the offending agents can be removed (phagocytized)

Question 31

Once leukocytes (primarily neutrophils and macrophages) have been recruited to a site of infection or cell death their functional properties must be activated so that the offending agents can be removed. This requires what?

Answer 31

recognition and attachment of the particle to be ingested by the leukocyte; engulfment with subsequent formation of a phagocytic vacuole; killing of the microbe and degradation of the ingested material

Question 32

Recognition of microbes or dead cells induces several response in leukocytes that are collectively called what?

Answer 32

leukocyte activation

Question 33

What are some examples of phagocytic receptors?

Answer 33

mannose receptors, scavenger receptors, and receptors for various opsonins

Question 34

What is the macrophage mannose receptor?

Answer 34

it is a lectin that binds terminal mannose and fructose residues- these sugars are typically part of molecules found on microbial cell walls

Question 35

What are scavenger receptors?

Answer 35

molecules that bind and mediate endocytosis of oxidized or acetylated low-density lipoprotein (LDL) particles that do not interact with the conventional LDL receptor

Question 36

The efficiency of phagocytosis is greatly enhanced when?

Answer 36

when microbes are opsonized by specific proteins

Question 37

what are the major opsonins?

Answer 37

IgG antibodies, the C3b breakdown product of complement, and mannose-binding lectin and collectins

Question 38

Once phagocytized, killing of microbes is accomplished how?

Answer 38

by reactive oxygen species (ROS) and reactive nitrogen species (mainly derived from nitric oxide); as well as lysosomal enzymes

Question 39

The other macromolecules destined for catabolism in the lysosomes arrive by one of three ways. What are these?

Answer 39

fluid-phase or receptor mediated endocytosis; autophagy; phagocytosis

Question 40

How are ROS produced?

Answer 40

by the rapid assembly and activation of NADPH oxidase

Question 41

In neutrophils, how is this oxidative reaction triggered? and what is this called?

Answer 41

by activating signals accompanying phagocytosis; called the respiratory burst

Question 42

How is NO produced?

Answer 42

from arginine by the action of NOS

Question 43

There are three different types of NOS, which type is involved in microbial killing?

Answer 43

iNOS- induced when macrophages are activated by cytokines

Question 44

Neutrophils and macrophages contain lysosomal granules that contribute to microbial killing and when released may cause tissue damage. Neutrophils have two main types of granules: What do the smaller specific (or secondary) lysosomal granules contain?

Answer 44

lysozyme, collagenase, gelatinase, lactoferrin plasminogen activator, histaminase, and alkaline phosphatase

Question 45

Neutrophils and macrophages contain lysosomal granules that contribute to microbial killing and when released may cause tissue damage. Neutrophils have two main types of granules: What are the larger granules called and what do they contain?

Answer 45

azurophil (or primary) lysosomal granules; contain myeloperoxidase, bactericidal factors, acid hydrolases, and neutral proteases

Question 46

Because of the destructive effects of lysosomal enzymes, the initial leukocytic infiltration, if unchecked, can potentiate further inflammation by damaging tissues; these harmful proteases however are normally controlled by what?

Answer 46

a system of antiproteases in the serum of tissue fluids

Question 47

What is the main antiprotease/ what is the major inhibitor of neutrophil elastase?

Answer 47

alpha-1-antitrypsin

Question 48

What happens if there is a deficiency of these inhibitors of neutrophil elastase?

Answer 48

sustained action of leukocyte proteases- they are at risk for emphysema due to destruction of elastic support fibers in the lung

Question 49

What does toxic granulation refer to?

Answer 49

changes in granulocyte cells seen on examination of the peripheral blood film of patients with inflammatory conditions; they are dark course granules found in granulocytes- particularly neutrophils

Question 50

when are toxic granulations commonly found?

Answer 50

in patients with sepsis

Question 51

What is the purpose of Neutrophil extracellular traps (NETs)?

Answer 51

they are extracellular fibrillar networks that concentrate antimicrobial substances at sites of infection and prevent the spread of the microbes by trapping them in fibrils

Question 52

What do the extracellular traps of the NETs consist of?

Answer 52

a viscous meshwork of nuclear chromatin that binds and concentrates granule proteins

Question 53

what happens in the process of NET formation?

Answer 53

the nuclei of the neutrophils is lost, leading to the death of the cells

Question 54

When have NETs been detected in the blood?

Answer 54

during sepsis, and it is believed that their formation in the circulation is dependent on platelet activation

Question 55

What cell type are also critical cells of chronic inflammation and tissue repair after inflammation has subsided?

Answer 55

macrophages

Question 56

What cell type of adaptive immunity contributes to acute inflammation?

Answer 56

T lymphocytes- specifically Th17 cells (they produce IL-17)

Question 57

What happens in the absence of effective Th17 responses?

Answer 57

individuals are susceptible to fungal and bacterial infections, and they tend to develop “cold abscesses” particularly in the skin that lack the classic features of acute inflammation

Question 58

What are the active termination mechanisms of inflammation?

Answer 58

a switch in the type of arachidonic acid metabolite produce, from pro-inflammatory leukotrienes to anti-inflammatory lipoxins, and the liberation of anti-inflammatory cytokines (TGF-beta and IL-10)