Lecture 13: Leukocyte Migration and Inflammation

Question 1

Chemokines are small soluble proteins that induce directional ____ and activation of leukocytes. They are produced as ______ precursors that undergo intracellular ______ before being secreted.

Answer 1

MIGRATION

INACTIVE

CLEAVAGE

Question 2

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.

Answer 2

LOW

GLYCOSAMINOGLYCANS

NEGATIVELY

ENDOTHELIAL

Question 3

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.

Answer 3

G-protein

3

3

N-terminus

C-terminus

Question 4

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.)

Answer 4

GDP

GTP

CHEMOTAXIS

Question 5

Different leukocytes express different combinations of chemokine receptors. Inactive T-cells typically express only _____4, but when activated by _____, they upregulate other chemokine receptors.

Answer 5

CXCR4

IL-2

Question 6

Chemokines play two critical roles in the immune response:

1. Lymphocyte _____ and homing
2. initiation of _____ responses

Answer 6

1. RECIRCULATION

2. INFLAMMATORY

Question 7

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.

Answer 7

high ENDOTHELIAL VENULES

AFFERENT lymphatics

EFFERENT lymphatics

THORACIC

Question 8

There are two functional classifications of chemokines:

1. _______ (constitutively active)
2. ______ (induced by infection.)

Answer 8

1. HOMEOSTATIC

2. INFLAMMATORY

Question 9

There are 3 main types of Cell Adhesion Molecules (CAMs):

1. _____
2. _____
3. _____

Answer 9

1. SELECTINS
2. INTEGRINS
3. Ig-SUPERFAMILY CAMs (ICAMs)

Question 10

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.

Answer 10

CARBOHYDRATE

SERINE

THREONINE

Question 11

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.

Answer 11

HETEROdimers

CHEMOKINES

HIGH

ICAMs

Question 12

What does Homing refer to?

Answer 12

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.

Question 13

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.

Answer 13

HOME

MEMORY

Question 14

When DCs take up antigen, they upregulate CCR___, which is attracted to the constitutively expressed CCL___/CCL____ in the lymph nodes.

Answer 14

CCR7

CCL19/CCL21

Question 15

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.

Answer 15

MACROPHAGE

Question 16

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.

Answer 16

HAGEMAN factor

THROMBIN

Question 17

Lipid mediators of inflammation also increase vascular _____ and migration of _____.

Answer 17

PERMEABILITY

LEUKOCYTES

Question 18

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 _____.

Answer 18

SYSTEMIC

HYPOTHALAMUS

FEVER

Question 19

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.

Answer 19

OPSONIZATION

INCREASE

Question 20

Leucocyte Adhesion deficiency (LAD) is characterized by a deficiency in either CD___ or CD__, which are the two components of an ______ heterodimer.

Answer 20

CD11 or CD18

INTEGRIN

Question 21

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.

Answer 21

GP-120

CCR5