(answer a).In a rare congenital immunodeficiency disease, known as lym-
phocyte adhesion disease (LAD), patients suffer from recurrent bacterial
infections in which the leukocytes from affected children fail to adhere to
endothelial cells and migrate to the site of infection (answer c)due to
defects in the leukocyte integrin CD18 subunit. In different forms of LAD
there may be structural defects in the integrin molecule or a deficiency or
absence of CD18. Lymphocyte apoptosis (answer d)is not regulated
directly by integrins and plasma cells do not normally enter the blood
(answer e).The leukocyte adhesion cascade involves several precise
ordered steps: rolling, integrin activation and firm adhesion of the leuko-
cytes, all necessary prerequisites to transendothelial migration. Therefore,
in LAD, extravasation of leukocytes is not possible.
96.The answer is c.(Alberts, pp 1098–1102. Junqueira, pp 107.)Vitamin
C deficiency causes scurvy. The woman in the scenario is pregnant,
smokes, and has a diet deficient in fresh fruits and vegetables. Scurvy, or
vitamin C deficiency, results in an inability to form normal collagen triple
helices. In scurvy, the resulting collagen is less stable and is subject to
denaturation and proteolytic breakdown (answer a).That results partially
from slower secretion of collagen from fibroblasts. The collagen formed is
not normally hydroxylated at proline and lysine residues because of the
absence of vitamin C, which is a specific cofactor for hydroxylation of pro-
line and lysine (answer b).Bone structure and the dentition may be abnor-
mal and wound and fracture healing delayed (answer d).General tissue
instability may occur because collagen synthesis is necessary for mainte-
nance of structural support (answer e).Periodontal bleeding and ulcera-
tion are also common symptoms in scurvy.
97.The answer is d.(Alberts, pp1096–1102.) The fibrillar collagens
establish tensile strength at a number of levels including intra- and inter-
molecular cross-links. Covalent binding occurs through the OH−groups of
hydroxylysine and hydroxyproline and serves to stabilize the triple helix.
The triple helix (answer b)itself functions to resist tensile forces. The
degree of cross-linking varies from tissue to tissue. For example, it is highly
extensive in tendons. The organization of collagen in tissues also varies,
depending on function, from the layered appearance in bone to the axial
parallel bundles in tendons and the wickered pattern in skin. The interac-
tions with fibril-associated collagens (with interrupted triple helices) regulate
Connective Tissue Answers 187