Lecture 13: Leukocyte Migration and Inflammation Flashcards
Chemokines are small soluble proteins that induce directional ____ and activation of leukocytes. They are produced as ______ precursors that undergo intracellular ______ before being secreted.
MIGRATION
INACTIVE
CLEAVAGE
The C-terminus of chemokines bind with ____ affinity to __________ (GAGs) and other _______ charged sugar molecules on cell surfaces and tissue matrix glycoproteins. This allows chemokines to adsorb onto ______ cells in blood vessels, connective tissues, and extracellular matrices.
LOW
GLYCOSAMINOGLYCANS
NEGATIVELY
ENDOTHELIAL
Chemokine receptors are ____-protein coupled receptors with ____ (#) extracellular domains and ____ (#) intracellular domains. The N-terminus of the receptor is extracellular and associates with the ___-terminus of the chemokine. The ___-terminus of the chemokine, itself, associates with GAGs.
G-protein
3
3
N-terminus
C-terminus
When chemokines bind their receptors, this activates the receptor and causes the substitution of ____ with ____ on the alpha subunit. Downstream effects of this receptor activation lead to _______ (cell movement.)
GDP
GTP
CHEMOTAXIS
Different leukocytes express different combinations of chemokine receptors. Inactive T-cells typically express only _____4, but when activated by _____, they upregulate other chemokine receptors.
CXCR4
IL-2
Chemokines play two critical roles in the immune response:
- Lymphocyte _____ and homing
- initiation of _____ responses
- RECIRCULATION
2. INFLAMMATORY
From the arterial blood, Naive T-cells typically enter lymph nodes through high ______ ______. Few naive T-cells and DCs with antigen can enter through _____ lymphatics. Activated T-cells leave lymph nodes via ______ lymphatics and return to the blood via the ______ duct.
high ENDOTHELIAL VENULES
AFFERENT lymphatics
EFFERENT lymphatics
THORACIC
There are two functional classifications of chemokines:
- _______ (constitutively active)
- ______ (induced by infection.)
- HOMEOSTATIC
2. INFLAMMATORY
There are 3 main types of Cell Adhesion Molecules (CAMs):
- _____
- _____
- _____
- SELECTINS
- INTEGRINS
- Ig-SUPERFAMILY CAMs (ICAMs)
Selectins are responsible for the initial contact between endothelial cells and leukocytes through their binding to the ______ domains of glyocsylated proteins (mucin-like CAMs)that are rich in the amino acids ______ and ______. Keep in mind Selectins, themselves, are glycoproteins.
CARBOHYDRATE
SERINE
THREONINE
Integrins noncovalently linked _____dimers. Their activation is mediated by _____ binding to their receptors (“Inside-out activation”), and leads to _____ affinity binding of extracellular matrix, specifically to ______. This interaction is what allows for tight adherence of immune cells to the vascular endothelium.
HETEROdimers
CHEMOKINES
HIGH
ICAMs
What does Homing refer to?
The tendency of lymphocytes activated in a particular area to preferentially return to that same area. For example, if a lymphocyte is activated in lymph nodes by the lung, the lymphocyte preferentially returns to the lung tissue.
Effector T-cells express different sets of CAMs, and this is what allows them to _____ to particular areas. The same is true for Naive vs ______ T-cells. Remember that the association of CAMs is what allows lymphocytes to extravasate out of the blood and into tissues/lymph nodes.
HOME
MEMORY
When DCs take up antigen, they upregulate CCR___, which is attracted to the constitutively expressed CCL___/CCL____ in the lymph nodes.
CCR7
CCL19/CCL21
Neutrophils leave the blood and migrate to the sites off infection in a multi-step process (basically the same as lymphocytes) involving adhesive interactions that are regulated by _______-derived cytokines and chemokines.
MACROPHAGE
Plasma enzyme mediators, are activated in response to tissue damage. Initially, _____ factor is activated, which activates multiple pathways that lead to activation of ______ to initiate the clot response, complement activation, and an increase in leukocyte migration to the site of damage.
HAGEMAN factor
THROMBIN
Lipid mediators of inflammation also increase vascular _____ and migration of _____.
PERMEABILITY
LEUKOCYTES
Local acute inflammatory cytokines can enter the circulation and become part of the _____ acute phase response, causing changes in other tissues. For example, cytokines acting on the _____ can cause it to release prostaglandins and induce _____.
SYSTEMIC
HYPOTHALAMUS
FEVER
Systemic acute phase response can also include changes in the liver, which produces acute phase proteins that aid in ________ to increase phagocytosis, and in the bone marrow, which leads to an _____ in the release of immune cells from the marrow.
OPSONIZATION
INCREASE
Leucocyte Adhesion deficiency (LAD) is characterized by a deficiency in either CD___ or CD__, which are the two components of an ______ heterodimer.
CD11 or CD18
INTEGRIN
Viruses use chemokine mimics to gain entry into cells in a similar way that immune cells use them to extravasate. For example, HIV has an envelope protein GP-____ that binds to CCR___, which helps it enter cells.
GP-120
CCR5