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Symposium - Mycobacterial infection
TUBERCULOSIS SYMPOSIUM - HYCDBACTERIAL INFECTION The P a t h o l o g y o f M y c o b a c t e r i a l I n f e c t i o n Director o f Anatomical R o b i n Cooke, Pathology, Royal Brisbane Hospital, Australia
943, and 1003; l&@1122. Basu of hsasc.Wb S.lmden
IMMUNITY AND MYCOBACTERIAL 1NFECTlON : NEW GENERATION VACCINES FOR LEPROSY J.D. Watson. Department of Molecular Medicine. School of Medicine. University of Auckland. One of the greatest triumphs of medical science has been the development of vaccines that provide protective immunity from infectious diseases. These vaccines have bccn based on the isolation of the infectious agent and the subsequent inactivation or attenuation of the agent for use in immunization to yield immune response? of a protective nature. There are a number of diseases where this approach has led to immune responses but not to the development of protective immunity. These include a range of tropical diseases caused by protozoan parasites. leprosy. tuberculosis and AIDS. In developing a vaccine for leprosy there appear to be three relevant arguments to consider. First, most individuals who are infected with Mycobacterium leprae develop protective immunity and do not get clinical disease. Second. it is apparent that the clinical spectrum of disease can be correlated with cell-mediated immune responses to M.Ieprae. Third. while these observations are indicative that, in susceptible individuals. the immune response to M.leprae has a dramatic effect on the clinical spectrum of the disease, they do not throw light on the immunological difference behueen individuals that develop leprosy and t h o x who are infected but develop protective immunity. Analyses of recombinant proteins isolated from genomic libraries of M.leprae have yielded chemically-defined new immunologically-reactive epitopcs. These epitopcs are pcptides which are produced by degradation of bacterial proteins in antigen-presenting cells. The pcptides which represent the epitopcs associate with newly synthesized class I1 molecules of the major histocompatibility complex. I will describe our analysis of the 18kD protein antigen of Mycobacterium leprae and discuss ways that peptide fragments may be engineered into new vaccines and presented to individuals for immunization. The immunological basis of protective immunity will be reviewed.
Robert Koch identified the first mycobacterial organism - M.Tuberculosis. The main organs involved are lymph nodes, lung, central nervous system, abdominal viscera and j o i n t s . Ameur H a n s o n i d e n t i f i e d t h e n e x t member o f t h i s group - M.Leprae. This organism preferentially infects the cutaneous nerves, and as a result of the peripheral neuropathy there i s gross destruction of fingers and t o e s in a s s o c i a t i o n w i t h cutaneous d e f o r m i t i e s . More r e c e n t l y the group o f atypical mycobacteria were identified. These organisms grow more r a p i d l y t h a n t h e classical M.Tuberculosis and a t lower temperatures. The M.Ulcerans causes r a p i d l y extending undermixed u l c e r s of the skin. The M . S c r o f u l a c e u m causes c a s e a t i n g lymphadenopathy i n c h i l d r e n . T h e m o s t r e c e n t member o f t h i s g r o u p t o achieve prominence i s t h e M.Avis which infects patients with AIDS. This organism causes tissue necrosis with very l i t t l e cellular reaction. I t can easily be o v e r l o o k e d u n l e s s a Z e i h l N e i l s e n s t a i n i s done i n b i o p s i e s from a l l p a t i e n t s w i t h AIDS.
EPIDEMIOLOGY TRENDS INFECTIONS IN HONG KONG.
OF
MYCOBACTERIAL
AFB Cheng, Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. In Hong Kong, tuberculosis remains an important communicable disease. With continuing efforts in the prevention and control, both the number and rate of notifications showed a slight decline over the last ten years: from 162.1 cases per 100,000 population in 1979 to 123.6 per 100,000 in 1988. The overall male/female ratio was 2:l. The vulnerable ages for both sexes were between 20-30 years and above 55 years old. The most commonly involved site was the chest, followed by bones and joints, central nervous system, intestine and other. Death from tuberculosis continued to fall from 568 in 1976 to 388 in 1988 and the death rate from However, 12.8 to 6.8 per 1 D 0 , O O D population. tuberculosis still ranked eighth among the top ten causes of death in Hong Kong. The incidence of leprosy had also declined over the past decade from 74 cases in 1978 to 22 cases i n 1988 representing a reduction of the incidence rate from 1.6 to 0.4 per 100,000 population.
943, and 1003; l&@1122. Basu of hsasc.Wb S.lmden
IMMUNITY AND MYCOBACTERIAL 1NFECTlON : NEW GENERATION VACCINES FOR LEPROSY J.D. Watson. Department of Molecular Medicine. School of Medicine. University of Auckland. One of the greatest triumphs of medical science has been the development of vaccines that provide protective immunity from infectious diseases. These vaccines have bccn based on the isolation of the infectious agent and the subsequent inactivation or attenuation of the agent for use in immunization to yield immune response? of a protective nature. There are a number of diseases where this approach has led to immune responses but not to the development of protective immunity. These include a range of tropical diseases caused by protozoan parasites. leprosy. tuberculosis and AIDS. In developing a vaccine for leprosy there appear to be three relevant arguments to consider. First, most individuals who are infected with Mycobacterium leprae develop protective immunity and do not get clinical disease. Second. it is apparent that the clinical spectrum of disease can be correlated with cell-mediated immune responses to M.Ieprae. Third. while these observations are indicative that, in susceptible individuals. the immune response to M.leprae has a dramatic effect on the clinical spectrum of the disease, they do not throw light on the immunological difference behueen individuals that develop leprosy and t h o x who are infected but develop protective immunity. Analyses of recombinant proteins isolated from genomic libraries of M.leprae have yielded chemically-defined new immunologically-reactive epitopcs. These epitopcs are pcptides which are produced by degradation of bacterial proteins in antigen-presenting cells. The pcptides which represent the epitopcs associate with newly synthesized class I1 molecules of the major histocompatibility complex. I will describe our analysis of the 18kD protein antigen of Mycobacterium leprae and discuss ways that peptide fragments may be engineered into new vaccines and presented to individuals for immunization. The immunological basis of protective immunity will be reviewed.
Robert Koch identified the first mycobacterial organism - M.Tuberculosis. The main organs involved are lymph nodes, lung, central nervous system, abdominal viscera and j o i n t s . Ameur H a n s o n i d e n t i f i e d t h e n e x t member o f t h i s group - M.Leprae. This organism preferentially infects the cutaneous nerves, and as a result of the peripheral neuropathy there i s gross destruction of fingers and t o e s in a s s o c i a t i o n w i t h cutaneous d e f o r m i t i e s . More r e c e n t l y the group o f atypical mycobacteria were identified. These organisms grow more r a p i d l y t h a n t h e classical M.Tuberculosis and a t lower temperatures. The M.Ulcerans causes r a p i d l y extending undermixed u l c e r s of the skin. The M . S c r o f u l a c e u m causes c a s e a t i n g lymphadenopathy i n c h i l d r e n . T h e m o s t r e c e n t member o f t h i s g r o u p t o achieve prominence i s t h e M.Avis which infects patients with AIDS. This organism causes tissue necrosis with very l i t t l e cellular reaction. I t can easily be o v e r l o o k e d u n l e s s a Z e i h l N e i l s e n s t a i n i s done i n b i o p s i e s from a l l p a t i e n t s w i t h AIDS.
EPIDEMIOLOGY TRENDS INFECTIONS IN HONG KONG.
OF
MYCOBACTERIAL
AFB Cheng, Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. In Hong Kong, tuberculosis remains an important communicable disease. With continuing efforts in the prevention and control, both the number and rate of notifications showed a slight decline over the last ten years: from 162.1 cases per 100,000 population in 1979 to 123.6 per 100,000 in 1988. The overall male/female ratio was 2:l. The vulnerable ages for both sexes were between 20-30 years and above 55 years old. The most commonly involved site was the chest, followed by bones and joints, central nervous system, intestine and other. Death from tuberculosis continued to fall from 568 in 1976 to 388 in 1988 and the death rate from However, 12.8 to 6.8 per 1 D 0 , O O D population. tuberculosis still ranked eighth among the top ten causes of death in Hong Kong. The incidence of leprosy had also declined over the past decade from 74 cases in 1978 to 22 cases i n 1988 representing a reduction of the incidence rate from 1.6 to 0.4 per 100,000 population.