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IMMUNITY AND PATHOGENESIS OF THIRD WORLD DISEASES: 
LEPROSY AND TUBERCULOSIS 
Barry R. Bloom, Ph.D., Investigator 
For many years Dr. Bloom's laboratory has been 
investigating basic scientific problems of particular 
relevance to the Third World. Tuberculosis is the 
major infectious disease in the world today, result- 
ing in 3 million deaths and 8 million new cases an- 
nually. Leprosy afflicts 10-12 million people 
worldwide and produces deformity in 30%. Both 
diseases are caused by mycobacteria. The labora- 
tory is investigating the immune responses to 
these organisms and the molecular basis of their 
pathogenesis. 
Immunologic Unresponsiveness in Leprosy 
One unique aspect of leprosy is that it is not a 
single clinical entity, but rather forms a clinical 
spectrum. That spectrum correlates strongly with 
the degree of cellular immunity of the patients. In 
the tuberculoid form, the lesions, which may be 
few, can be healed by the immune response, though 
often at the price of damage to nerves. At the other 
end of the spectrum in the lepromatous form there 
is an almost total absence of cell-mediated immu- 
nity to antigens of Mycobacterium leprae, and the 
bacilli ineluctably multiply within macrophages 
and disseminate in prodigious numbers. What is the 
mechanism of the specific unresponsiveness to anti- 
gens of M. leprae in lepromatous patients? An un- 
derstanding of this immunologically fascinating 
phenomenon has relevance to the production of im- 
munological tolerance, or unresponsiveness, to or- 
gan grafts, cancers, autoimmune reactions, and 
other infectious diseases. 
Dr. Bloom's laboratory has found that T lympho- 
cytes from lepromatous, but not tuberculoid, pa- 
tients can suppress the proliferation of antigen- 
reactive T cells — i.e., cells that produce protective 
molecules such as interferon-7 (IFN-7) and inter- 
leukin-2 (IL-2). These suppressor cells have been 
identified by a specific surface marker, CDS, and by 
a unique mode of antigen recognition. Their ability 
to recognize antigen molecules is controlled by a 
specific component of the major histocompatibil- 
ity system known as HLA-DQ, whereas antigen- 
responding cells that produce protective responses 
recognize antigen in the context of another set of 
histocompatibility antigens, HLA-DR. 
Of particular interest. Dr. Bloom's group has 
found that suppressor cells produce a specific pat- 
tern of lymphokines, including IL-4 and IL-5, but 
not IFN-7. These cells and lymphokine patterns are 
found in skin lesions of patients with lepromatous 
leprosy. In contrast, protective T cells produce IFN- 
7 and IL-2, but not IL-4 and IL-5. These results point 
to the fact that there are different functional subsets 
of T cells in humans that can best be distinguished 
by the patterns of lymphokines they produce, and 
suggest that suppression and enhancement of spe- 
cific immune responses can in part be attributed to 
those lymphokines. 
Development of Recombinant BCG 
as a Multivaccine Vehicle 
Vaccines represent the most cost-effective medi- 
cal intervention in the world for preventing disease. 
BCG (bacillus Calmette-Guerin) vaccine, given to 
immunize against tuberculosis in most parts of the 
world, could serve as a vector for administering re- 
combinant foreign antigens. Among advantages are 
its widespread use, having been given to 2.5 billion 
people since 1948; the very low incidence of seri- 
ous side effects; the fact that it is one of the two 
vaccines that can be given at birth or any time there- 
after; its induction of long-term sensitization (5-50 
years, with a single shot); its potency as an adjuvant 
for animal and human use; and its extraordinarily 
low cost. 
IMMUNOLOGY 311 
