Inflammation and Leukocyte migration Flashcards
What are 4 symptoms of the inflammatory response
redness (rubor), heat (calor), swelling (tumor), and pain (dolor)
-also loss of function
What class of molecules are crucial for leukocyte-tissue interactions during inflammation?
Cell adhesion molecules (CAM)
What are 4 members of the CAM class
selectins, integrins, mucins, and immunoglobin-superfamily CAMs
4 steps of the basic inflammatory response following a cut or other tissue trauma
- Tissue damage and bacteria cause resident sentinel cells to release chemoattractants and vasoactive factors
- increase blood flow and permeability in the area - Influx of fluid (exudate) and cells into area
- Neutrophils and other phagocytes migrate by chemotaxis to the site of inflammation
- Phagocytes and antibacterial substances destroy bacteria
What causes bloodstream leukocytes to recognize the site of infection?
Interactions between selectins and mucins as well as integrins binding to CAMs on the endothelial cells
What is the composition of selectins and what is their role?
Glycoproteins that bind specific carbohydrate groups via lectin-like domains
What is the composition of mucins and what is their role?
Mucins are glycosylated proteins that present carbohydrate groups (like sialyl-Lewisx) to selectins
What is the composition of integrins and what is their role?
Cell surface heterodimeric proteins
Bind extracellular matrix molecules and intracellular cell adhesion molecules (ICAMs)
What are ICAMs? `
Immunoglobulin superfamily of glycoproteins that bind integrins
What is one important member of the Mucin-like CAM family?
MAdCAM-1
What is one important member of the Ig-superfamily CAMs?
VCAM-1
What are 3 important members of the Integrin family?
VLA-4, Mac-1, LFA-1
What are 3 general jobs of chemokines?
Control leukocyte adhesion, chemotaxis and activation
What is the mode(s) of chemokine expression
they are constitutively expressed but also produced in response to inflammation
What are the 2 subgroups of chemokines and what is this distinction based on?
CC and CXC subgroups based on the amino acid composition
What is the general structure of a chemokine receptor?
7 transmembrane proteins that signal via heterotrimeric G proteins
Each receptor can bind more than one chemokine
Which subgroup does MIP-1a belong to and what is its role?
MIP-1a:prevents the monocyte from leaving once it enters the tissue
Belongs to the CC subgroup (CCR5)8
What activates neutrophils?
Chemokines like IL-8
What causes endothelial cells to increase CAM expression?
Cytokines and other products of inflammation
what are the 4 steps of leukocyte extravasion? Which factors facillitate each step?
- Rolling - selectin/mucin interactions
- Activation of leukocyte - chemokines
- Arrest/adhesion to the endothelial cell - Integins/CAM interactions
- Transendothelial migration - integrin/ICAMs/Chemokines
* chemokines are sort of present at every step
Leukocytes only exit ____ into tissue
Veins
Recirculation of lymphocytes from the blood to the bone marrow, spleen, lymph nodes, and tertiary extralymphoid tissues occurs at least once every ….
24 hours in order for t and b cells to interact with foreign antigen
What does recirculation ensure?
Greatest number of antigen specific lymphocytes have the opportunity to encounter and interact with antigen
Migration of lymphocytes into lymph nodes take place across _____ venules
High endothelial
What interactions between the lymphocyte and the endothelial layer of promote rolling in transendothelial migration?
Between lymphocyte L-selectin and endothelial cell mucin
Which factor mediates lymphocyte arrest in transendothelial migration?
Integrins
- helps it adhere to the ICAMs
- ex: LFA-1 (integrin)
- ex: ICAM-1
What do junctional adhesion molecules to?
Mediate transendothelial migration
-ex: PECAM-1
What is the role of homing receptors?
Are located on lymphocytes
Recognize specific CAMs and mediate the differential migration of lymphocyte subsets into different tissues of the lymph node
What is the role of MIP-1ß
chemokine involved in lymphocyte homing that attracts naive T cells
What is the role of RANTES?
chemokine involved in lymphocyte homing that attracts memory T cells
Which kinds of lymphocytes do not show tissue specific homing?
Naive lymphocytes
Where to effector lymphocytes home to?
sites of inflammation
Where do memory lymphocytes home to ?
The tissue type in which the specific antigen was first encountered
Name 3 important lipid mediators of inflammation
- Prostaglandins
- Leukotrienes
- Thromboxane
Which mediator causes vasoconstriction and platelet aggregation?
Thromboxane
Which meditators are involved in lung inflammation
Leukotrienes C4, D4, E4
What does leukotriene B4 cause
Neutrophil chemotaxis
What 3 things does platelet activating factor cause
- Platelet aggregation
- neutrophil activation
- eosinophiil chemotaxis
What are the 3 main effects of prostaglandins
- Increased vascular permeability
- Vascular dialation
- Neutrophil chemotaxis
What mediator attracts leukocytes (many subsets) to sites of inflammation and regulates CAM expression and conformation?
Chemokines
What do anaphylatoxins trigger?
Mast cell release of histamine
What is the effect of histamine?
Smooth muscle contraction and increased vascular permeability
What are 3 examples of proinflammatory cytokines?
TNFα, IL-1 and IL-6
What is the effect of the proinflammatory cytokines?
- induce fever
- actute phase protein synthesis
- increased CAM expression
- increased vascular permeability during acute inflammation
What two cytokines are important in chronic inflammation leading to tissue damage?
Interferon-γ and TNFα
