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The SCID home page contains links to periodicals and databases with information about SCID.
This site from the National Insitute for Human Genome Research includes a database of mutations in X-linked SCID.
Information about the global AIDS epidemic can be accessed from this site.
Up-to-date information concerning AIDS epidemiology in the United States can be obtained at this site.
Web site maintained by the Los Alamos National laboratories containing all available sequence data on HIV and SIV along with up-to-date reviews on topics of current interest to AIDS research.
A listing with detailed information for several hundred drugs under development for HIV infection and opportunistic infections associated with AIDS; maintained by the National Library of Medicine.
Information about AIDS vaccines from the National Institute of Allergy and Infectious Diseases, NIH. Includes links to documents about vaccines in general.
Clinical Focus Question The spread of HIV/AIDS from infected mothers to infants can be reduced by single-dose regimens of the reverse transcriptase inhibitor Nevirapine. What would you want to know before giving this drug to all mothers and infants (without checking infection status) at delivery in areas of high endemic infection?
1. Indicate whether each of the following statements is true or false. If you think a statement is false, explain why.
a. DiGeorge syndrome is a congenital birth defect resulting in absence of the thymus.
b. X-linked agammaglobulinemia (XLA) is a combined B-cell and T-cell immunodeficiency disease.
c. The hallmark of a phagocytic deficiency is increased susceptibility to viral infections.
d. In chronic granulomatous disease, the underlying defect is in a cytochrome or an associated protein.
e. Injections of immunoglobulins are given to treat individuals with X-linked agammaglobulinemia.
f. Multiple defects have been identified in human SCID.
g. Mice with the SCID defect lack functional B and T lymphocytes.
h. Mice with SCID-like phenotype can be produced by knockout of RAG genes.
i. Children born with SCID often manifest increased infections by encapsulated bacteria in the first months of life.
j. Failure to express class II MHC molecules in bare-lymphocyte syndrome affects cell-mediated immunity only.
2. Granulocytes from patients with leukocyte-adhesion deficiency (LAD) express greatly reduced amounts of three in-tegrin molecules designated CR3, CR4, and LFA-1.
a. What is the nature of the defect that results in decreased expression or in no expression of these receptors in LAD patients?
b. What is the normal function of the integrin molecule LFA-1? Give specific examples.
3. Immunologists have studied the defect in SCID mice in an effort to understand the molecular basis for severe combined immunodeficiency in humans. In both SCID mice and humans with this disorder, mature B and T cells fail to develop.
a. In what way do rearranged Ig heavy-chain genes in SCID mice differ from those in normal mice?
b. In SCID mice, rearrangement of k light-chain DNA is not attempted. Explain why.
c. If you introduced a rearranged, functional ^ heavy-chain gene into progenitor B cells of SCID mice, would the k light-chain DNA undergo a normal rearrangement? Explain your answer.
4. The accompanying figure outlines some of the steps in the development of immune-system cells. The numbered arrows indicate the cell type whose function is defective or the developmental step that does not occur in particular immunodeficiency diseases. Identify the defective cell type or developmental step associated with each of the following diseases. Use each number only once.
Myeloid progenitor Lymphoid progenitor
> Neutrophil Monocyte Pre-T cell Pre-B cell ©
-> Mature T cell Mature B cell o
Plasma cell a. Chronic granulomatous disease b. Severe combined immunodeficiency disease (SCID)
c. Congenital agranulocytosis d. Reticular dysgenesis e. Common variable hypogammaglobulinemia f. X-linked agammaglobulinemia g. Leukocyte-adhesion deficiency (LAD)
h. Bare-lymphocyte syndrome
5. Indicate whether each of the following statements is true or false. If you think a statement is false, explain why.
a. HIV-1 and HIV-2 are more closely related to each other than to SIV.
b. HIV-1 causes immune suppression in both humans and chimpanzees.
c. SIV is endemic in the African green monkey.
d. The anti-HIV drugs zidovudine and indinavir both act on the same point in the viral replication cycle.
e. T-cell activation increases transcription of the HIV proviral genome.
f. Patients with advanced stages of AIDS always have detectable antibody to HIV.
g. The polymerase chain reaction is a sensitive test used to detect antibodies to HIV.
h. If HAART is successful, viral load will decrease.
6. Various mechanisms have been proposed to account for the decrease in the numbers of CD4+ T cells in HIV-infected individuals. What seems to be the most likely reason for depletion of CD4+ T cells?
7. Would you expect the viral load in the blood of HIV-infected individuals in the chronic phase of HIV-1 infection to vary?
8. If viral load begins to increase in the blood of an HIV-infected individual and the level of CD4+ T cells decrease, what would this indicate about the infection?
9. Why do clinicians monitor the level of skin-test reactivity in HIV-infected individuals? What change might you expect to see in skin-test reactivity with progression into AIDS?
10. Certain chemokines have been shown to suppress infection of cells by HIV, and pro-inflammatory cytokines enhance cell infection. What is the explanation for this?
11. Treatments with combinations of anti-HIV drugs (HAART) have reduced virus levels significantly in some treated patients and delayed the onset of AIDS. If an AIDS patient becomes free of opportunistic infection and has no detectable virus in the circulation, can that person be considered cured?
12. Suppose you are a physician who has two HIV-infected patients. Patient B. W. has a fungal infection (candidiasis) in the mouth, and patient L. S. has a Mycobacterium infection. The CD4+ T-cell counts of both patients are about 250 per mm3. Would you diagnose either patient or both of them as having AIDS?
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