The Immunology of Human Reproduction PDF

Preface

The main function of the immune system is to defend the body against invasion by bacteria, viruses and other pathogenic organisms. The immune system is also thought to mount surveillance against malignancy. In other words, pathogens and malignant cells are ‘foreign' or ‘non-self', and, therefore, the fundamental function of the immune system is to recognize and eliminate ‘non-self'. This fundamental function raises a major issue with regard to human pregnancy: the human fetus, which is essentially ‘non-self' as it derives half its genetic information from the father, is not treated as ‘non-self' and eliminated, but in fact is welcomed, nourished for 9 months and then nurtured for the next 18 years! Why the fetus is not eliminated by the immune system of the mother has puzzled and fascinated biologists for years, and has given rise to the subject of reproductive immunology. The paradox became acutely apparent in the late 1940s/early 1950s following discovery of the laws of transplantation immunology by Peter Medawar and his colleagues. Medawar himself, probably one of the greatest immunologists as well as a philosopher, crystallized the paradox in these words: ‘The immunological problem of pregnancy may be formulated thus: How does the pregnant mother contrive to nourish within itself, for many months or weeks, a fetus that is an antigenically foreign body?'

Many have speculated on the wide-ranging benefits that might accrue from the unraveling of the mechanisms by which the fetus eludes the maternal immune system. Rational strategies might evolve for the treatment of diseases of pregnancy thought to have an immunological basis (e.g. recurrent spontaneous miscarriage, pre-eclampsia and intrauterine growth restriction); organ transplantation programs might benefit by emulating nature's strategies in creating a perfect allograft; clues might emerge as to how tumors escape immunosurveillance, and new treatments might therefore be developed.

Peter Medawar's thinking on this matter has dominated ideas on the maternal—fetal immunological relationship to this day. Medawar himself conducted no research to try to resolve the paradox, but suggested that the placenta must play a central role in fetal survival, as the trophoblast cells interface with the mother. However, his other proposals—maternal immunosuppression and immaturity of fetal antigens—together with subsequent diverse hypotheses by others have not withstood the test of time. Probably central to the failure to arrive at a conclusive resolution of this paradox is the fact that the fetus should really not be considered an allograft in the conventional sense. While the adaptive immune response would be central to conventional concepts of the rejection of an allograft, recent research in reproductive immunology would suggest that the innate immune system might, in fact, play a more important role in the maternal— fetal immunological relationship. These and other issues are explored in this book, which is aimed at readers, predominantly obstetricians and gynecologists, who are often daunted by the subject of immunology, yet wish to gain a better understanding of the subject. It is not intended as a detailed exposé on immunology, nor does it intend to deal with state-ofthe- art research in the field of reproductive immunology. Rather, the aim is to equip the reader with sufficient knowledge of immunological concepts to allow an understanding of the current thinking and approaches to reproductive immunology. Further reading is suggested where appropriate.