Online Mendelian Inheritance in Man is a catalog of human genes and genetic disorders. It contains pictures and references on many diseases, including LAD.
Clinical Focus Question Why does a defect in CD18 result in an increased vulnerability to bacterial infection? Please address, as precisely as you can, the cell biology of cell migration.
1. Indicate whether each of the following statements is true or false. If you think a statement is false, explain why.
b. Integrins are expressed on both leukocytes and endothe-lial cells.
c. Leukocyte extravasation involves multiple interactions between cell-adhesion molecules.
d. Most secondary lymphoid organs contain high-endothe-lial venules (HEVs).
f. An acute inflammatory response involves only localized effects in the region of tissue injury or infection.
g. MAdCAM-1 is an endothelial adhesion molecule that binds to L-selectin and to several integrins.
2. Various inflammatory mediators induce expression ofICAMs on a wide variety of tissues. What effect might this induction have on the localization of immune cells?
3. Extravasation of neutrophils and of lymphocytes occurs by generally similar mechanisms, although some differences distinguish the two processes.
a. List in order the four basic steps in leukocyte extravasation.
b. At which sites are neutrophils most likely to extravasate? Why?
c. Different lymphocyte subpopulations migrate preferentially into different tissues, a process called homing (or trafficking). Discuss the roles of the three types of molecules that permit homing of lymphocytes.
4. Which three cytokines secreted by activated macrophages play a major role in mediating the localized and systemic effects associated with an acute inflammatory response?
5. An effective inflammatory response requires differentiation and proliferation of various nonlymphoid white blood cells. Explain how hematopoiesis in the bone marrow is induced by tissue injury or local infection.
6. For each pair of molecules listed below, indicate whether the molecules interact during the 1st, 2nd, 3rd, or 4th step in neutrophil extravasation at an inflammatory site. Use N to indicate any molecules that do not interact.
a. _Chemokine and L-selectin b. _E-selectin and mucin-like CAM
c. _IL-8 and E-selectin d. _Ig-superfamily CAM and integrin e. ICAM and chemokine f. _Chemokine and G-protein-coupled receptor g. ICAM and integrin
7. Discuss the main effects of IFN-7 and TNF-a during a chronic inflammatory response.
8. Five cytokines (IL-1, IL-6, TNF-a, LIF, and OSM) induce production of C-reactive protein and other acute-phase proteins by hepatocytes. Briefly explain how these different cytokines can exert the same effect on hepatocytes.
9. For each inflammation-related term (a-h), select the descriptions listed below (1-11) that apply. Each description may be used once, more than once, or not at all; more than one description may apply to some terms.
Terms a. _Tertiary extralymphoid tissue b. _P- and E-selectin c. _Prostaglandins d. _Nonsteroidal anti-inflammatory drugs e. _ICAM-1, -2, -3
g. _Bradykinin h. Inflamed endothelium
(1) Bind to sialylated carbohydrate moieties
(2) Inhibit cyclooxygenase pathway
(3) Induce expression of NF-kB inhibitor
(4) Has both Ig domains and mucin-like domains
(5) Region of vascular endothelium found in postcapillary venules
(6) Expressed by inflamed endothelium
(7) Exhibits HEV-like vasculature in chronic inflammation
(8) Belong to Ig-superfamily of CAMs
(9) Exhibits increased expression of CAMs
(10) Increase vascular permeability and induce fever
(11) Induce fever
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