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Nobel prize in medicine awarded for insights into immune response
THE LANCET
SCIENCE AND MEDICINE
Nobel prize in medicine awarded for insights into immune response
T
he Nobel prize in physiology or medicine for 1996, announced on Oct 7, has been awarded to Rolf Zinkernagel (University of Zurich, Switzerland) and Peter Doherty (St Jude Children’s Research Hospital, Memphis, USA) for work on the specificity of cell-mediated immune defence. Doherty and Zinkernagel will receive the prize in recognition of work done in Australia in the mid1970s. Although the role of antibody-mediated immunity in clearing infections caused by some microorganisms was relatively well understood at that time, cell-mediated immunity was still largely a black box. It was known that T-lymphocytes could kill foreign cells in transplants by recognising
mismatches in the major histocompatibility antigens. But how did the cellular immune system fight infections by viruses? In their experiments, Zinkernagel and Doherty showed that lymphocytes recognise viral antigens only in the context of self molecules, the same major histocompatibility antigens implicated in graft rejection. So, when mice of a one strain were infected with a virus, the mice developed T lymphocytes capable of killing virus-infected cells but only if the infected cells were from the same strain of mice. Both the viral antigen and a self-antigen
were necessary for T-cell recognition and cell killing. In the 20 years since Doherty and Zinkernagel’s discovery, great strides have been made in understanding how the immune system learns to recognise self and how the immune system is regulated. This knowledge is important for the development of new vaccines against infectious organisms and for the development of cancer vaccines. And the greater understanding of cellular immunity pioneered by Zinkernagel and Doherty is now helping in the development of novel strategies for the treatment of chronic inflammatory diseases. Jane Bradbury
Can HIV-1 transmission be prevented during pregnancy and labour?
A
French study seeking to identify risk factors for mother-to-child transmission of HIV-1 has found that risks cannot be generally reduced by changes in obstetric management. The prospective cohort study, which included the SEROGEST and French Pediatric Cohorts, looked at the pregnancy and delivery history, and the HIV-1 status at 18 months of age of 1632 singleton children born to HIV-1-infected mothers (Am J Obstet Gynecol 1996; 175: 661–67). The data were collected before zidovudine use was introduced to prevent mother-to-child viral transmission. 19% of the children were seropositive at 18 months. Laurent Mandelbrot (Paris,
France) and colleagues found that the risk of transmission was higher when invasive procedures—eg, amniocentesis and amnioscopy—had been used. Sexually transmitted diseases during pregnancy, preterm delivery, premature membrane rupture, haemorrhage during labour, and blood in the amniotic fluid were also associated with increased transmission. The researchers note that, except for the invasive procedures, caregivers have little control over these factors. Risk factors over which caregivers have some control had little influence on outcome. Instrumental or protracted labour, fetal skin abrasions, episiotomy or perineal tears—all of
which increase direct fetal exposure to maternal blood—were not related to HIV-1 transmission, say the researchers. In particular, caesarean section gave no protection. The researchers conclude that few recommendations can be made other than that invasive procedures, such as amniocentesis, be avoided during pregnancy and that vaginal infections be promptly diagnosed and treated. “When premature rupture of membranes does occur, rapid delivery may be an option; however, it is not known whether the risk of HIV transmission follows or precedes premature membrane rupture.” Michael McCarthy
Lipoprotein(a) link to acute myocardial infarction investigated further
T
he results of the largest ever study of lipoprotein(a) values in acute myocardial infarction (AMI) suggest that elevated lipoprotein(a) may be the result of coronary artery damage rather than one of its causes (J Am Coll Cardiol 1996; 28: 870–75). In a population-based case-control study, lipoprotein(a) values were measured in 893 men and women aged between 35 and 69. The cases, presenting with either a first or
Vol 348 • October 12, 1996
recurrent AMI, were participants in the WHO’s Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project. The controls were also divided into those with and without a history of AMI. Patient groups and controls with a history of AMI had higher lipoprotein(a) values than controls with no history, but the increase was not significant for people having their first AMI. Lipoprotein(a) values higher than 550 mg/L were a risk factor for
first, but not recurrent, AMI (odds ratio of 2·51 for women, 1·44 for men). Although elevated lipoprotein(a) has been proposed as a risk factor for both first and recurrent AMI, the authors of this new report say that their results indicate that elevated lipoprotein(a) is, instead, a marker of tissue damage, and that its routine measurement may not be useful in AMI risk assessment. Susan Aldridge
1021
SCIENCE AND MEDICINE
Nobel prize in medicine awarded for insights into immune response
T
he Nobel prize in physiology or medicine for 1996, announced on Oct 7, has been awarded to Rolf Zinkernagel (University of Zurich, Switzerland) and Peter Doherty (St Jude Children’s Research Hospital, Memphis, USA) for work on the specificity of cell-mediated immune defence. Doherty and Zinkernagel will receive the prize in recognition of work done in Australia in the mid1970s. Although the role of antibody-mediated immunity in clearing infections caused by some microorganisms was relatively well understood at that time, cell-mediated immunity was still largely a black box. It was known that T-lymphocytes could kill foreign cells in transplants by recognising
mismatches in the major histocompatibility antigens. But how did the cellular immune system fight infections by viruses? In their experiments, Zinkernagel and Doherty showed that lymphocytes recognise viral antigens only in the context of self molecules, the same major histocompatibility antigens implicated in graft rejection. So, when mice of a one strain were infected with a virus, the mice developed T lymphocytes capable of killing virus-infected cells but only if the infected cells were from the same strain of mice. Both the viral antigen and a self-antigen
were necessary for T-cell recognition and cell killing. In the 20 years since Doherty and Zinkernagel’s discovery, great strides have been made in understanding how the immune system learns to recognise self and how the immune system is regulated. This knowledge is important for the development of new vaccines against infectious organisms and for the development of cancer vaccines. And the greater understanding of cellular immunity pioneered by Zinkernagel and Doherty is now helping in the development of novel strategies for the treatment of chronic inflammatory diseases. Jane Bradbury
Can HIV-1 transmission be prevented during pregnancy and labour?
A
French study seeking to identify risk factors for mother-to-child transmission of HIV-1 has found that risks cannot be generally reduced by changes in obstetric management. The prospective cohort study, which included the SEROGEST and French Pediatric Cohorts, looked at the pregnancy and delivery history, and the HIV-1 status at 18 months of age of 1632 singleton children born to HIV-1-infected mothers (Am J Obstet Gynecol 1996; 175: 661–67). The data were collected before zidovudine use was introduced to prevent mother-to-child viral transmission. 19% of the children were seropositive at 18 months. Laurent Mandelbrot (Paris,
France) and colleagues found that the risk of transmission was higher when invasive procedures—eg, amniocentesis and amnioscopy—had been used. Sexually transmitted diseases during pregnancy, preterm delivery, premature membrane rupture, haemorrhage during labour, and blood in the amniotic fluid were also associated with increased transmission. The researchers note that, except for the invasive procedures, caregivers have little control over these factors. Risk factors over which caregivers have some control had little influence on outcome. Instrumental or protracted labour, fetal skin abrasions, episiotomy or perineal tears—all of
which increase direct fetal exposure to maternal blood—were not related to HIV-1 transmission, say the researchers. In particular, caesarean section gave no protection. The researchers conclude that few recommendations can be made other than that invasive procedures, such as amniocentesis, be avoided during pregnancy and that vaginal infections be promptly diagnosed and treated. “When premature rupture of membranes does occur, rapid delivery may be an option; however, it is not known whether the risk of HIV transmission follows or precedes premature membrane rupture.” Michael McCarthy
Lipoprotein(a) link to acute myocardial infarction investigated further
T
he results of the largest ever study of lipoprotein(a) values in acute myocardial infarction (AMI) suggest that elevated lipoprotein(a) may be the result of coronary artery damage rather than one of its causes (J Am Coll Cardiol 1996; 28: 870–75). In a population-based case-control study, lipoprotein(a) values were measured in 893 men and women aged between 35 and 69. The cases, presenting with either a first or
Vol 348 • October 12, 1996
recurrent AMI, were participants in the WHO’s Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project. The controls were also divided into those with and without a history of AMI. Patient groups and controls with a history of AMI had higher lipoprotein(a) values than controls with no history, but the increase was not significant for people having their first AMI. Lipoprotein(a) values higher than 550 mg/L were a risk factor for
first, but not recurrent, AMI (odds ratio of 2·51 for women, 1·44 for men). Although elevated lipoprotein(a) has been proposed as a risk factor for both first and recurrent AMI, the authors of this new report say that their results indicate that elevated lipoprotein(a) is, instead, a marker of tissue damage, and that its routine measurement may not be useful in AMI risk assessment. Susan Aldridge
1021