Inflammation and Leukocyte Migration

Question 1

Inflammatory response

Answer 1

Results from local injury or tissue trauma
Characterized by redness, heat, swelling, pain
Involves leukocytes and soluble/membane bound molecules
CAMs are important for leukocyte-tissue interactions

Question 2

CAMs

Answer 2

Cell Adhesion Molecules

Selectin, mucins, integrins, immunoglobulin-superfamily CAMs

Question 3

L-Selectin

Answer 3

Helps with rolling of neutrophils

Neutrophils are first responders at site of inflammation

Question 4

Selectins

Answer 4

Glycoproteins that bind to specific carbohydrate groups ie. sialyl-lewisx by lectin-like domain

Question 5

Mucins

Answer 5

Glycosylated proteins that present sialyl-Lewisx and other carbohydrate groups to selectins

Question 6

Integrins

Answer 6

Cell-surface heterodimeric proteins that bind extracellular matrix molecules and intracellular adhesion molecules

Question 7

ICAMs

Answer 7

Immunoglobulin-superfamily glycoproteins that bind integrins

Question 8

Chemokines

Answer 8

Control leukocyte adhesion, chemotaxis and activation
Constitutively expressed and are also produced in response to inflammation: induced at the time of injury
Most belong to CC or CXC subgroups (based on composition)
Chemokine receptors are 7 transmembrane proteins that signal through G proteins
Individual receptors are able to bind more than one chemokine
Receptor expression is limited to certain cell types

Question 9

Leukocyte migration

Answer 9

Enter sites of inflammation by leukocyte extravasation
Cytokines and other inflammatory products cause endothelial cells to increase CAM expression
Neutrophil rolling is promoted by selectin-mucin interactions
Intergins on activated neutrophils (by IL8) assume high affinity conformation
Chemoattractants and CAM interactions mediate transendothelial migration of leukocytes
ONLY VEINS

Question 10

Inflamed endothelium

Answer 10

Expressing adhesion molecules

Question 11

Lymphocyte extravasation

Answer 11

Migration of lymphocytes into lymph nodes across high endothelial venues
Rolling is promoted by weak interactions between lymphocyte L-selectin and endothelial cell mucin
Chemokine constitutively expressed by endothelial cells case integrins to adopt high affinity conformation
Integrins mediate lymphocyte arrest and adhesion of immunoglobulin superfamily CAMs
Junction adhesion molecules
T cells: paracortex
B cells: follicle

Question 12

Lymphocyte homing

Answer 12

Homing receptors on lymphocytes recognize specific CAMs: drive migration to specific areas
MIP-1beta attracts naive T cells
RANTES attracts memory T cells
Naive lymphocytes do not show specific tissue homing
Effector lymphocytes home to sites of inflammation
Memory lymphocytes home to tissue type where antigen was first encountered

Question 13

Lipid mediators of inflammation

Answer 13

Thromboxane, prostaglandins, leukotrienes

Question 14

Thromboxanes

Answer 14

Cause vasoconstriction and platelet aggregation

Question 15

Prostaglandins

Answer 15

Increase vascular permeability, vascular dilation and neutrophil chemotaxis

Question 16

Leukotrienes C4, D4, E4

Answer 16

Mediate lung inflammation

Question 17

Leukotriene B4

Answer 17

Cause neutrophil chemotaxis

Question 18

Platelet activating factor

Answer 18

Causes platelet aggregation, neutrophil activation and eosinophil chemotaxis

Question 19

Anaphylatoxins

Answer 19

Trigger tissue mast cell release of histamine leading to smooth muscle contraction and increase vascular permeability

Question 20

Pro inflammatory cytokines

Answer 20

TNFalpha, IL1, IL6
Induce fever, acute phase protein synthesis, increased CAM expression, increased vascular permeability in acute inflammation

Question 21

Chronic inflammation - tissue damage

Answer 21

Interferon gamma and TNFalpha are important