Preface Reproductive immunology is a hybrid discipline involving reproduction on one side and immunology on the other side. Efficient reproduction is the greatest biological problem for the livestock production. Immunology is a powerful tool for studying normal fertility and infertility. In the field of reproductive immunology, one major issue is to explore the successful gestation of the histocompatible foetus in the uterus of an immunological competent mother, major immunological causes that interfere with the conception rate in animals. This book, shows how immunology relates to fertility  or infertility in the bovines and other livestock. It is with immense pleasure that this book, “Immunology of Animal Reproduction” is brought out. There has been veritable explosion in human reproductive immunology- a subject which occupies a prime position in human reproduction. The impetus for this book evolved from a recognized need for a comprehensive note to provide the basic understanding of the complex description of the immunology of animal reproduction which is otherwise to scanty available information. A little information is available on different sources especially websites. But comprehensive and up-to-date information needed by the scientists, teachers, students of undergraduate and postgraduate in biology, veterinary and veterinarians in general is found to be the need of the hour. Considering the necessity, I thought of bringing a text with comprehensive information in a simpler way.

Reproduction is one of the most serious biological problems that markedly influence the efficiency of livestock production. Immunology is a powerful tool for studying both normal fertility and infertility of farm animals. Reproductive immunology is in turn is an important tool for unlocking normal fertility problems and various forms of infertility or reproductive disorders. Although the immune and reproduction systems have been considered independent of each other, the cooperation of both the systems is crucial for initiation and maintenance of mammalian pregnancy. Therefore, reproductive immunology has now become a mature discipline and a major theme during advances in the field of reproductive immunology is to explain the successful gestation of the histcompatable mammalian embryos within the uterus of its immunologically competent mother.   Immune responses play an important role in various reproductive processes, including ovulation, menstruation and parturition. Clearly, during pregnancy, when the mother must accept a semi-allogeneic foetus, immune responses also play a very important role which  was first recognized by Medawar in 1953, when the concept of the foetal allograft was presented in order to explain the immunological relationship between mother and foetus. Since then, the immunology of pregnancy has been the leading subject within reproductive immunology research.

1. TYPES AND GRADES OF IMMUNITY The immune response, which has inherited the character of memory, as evinced by rapidity and specificity of the responses on the second exposure to antigen, was cleared the minds of scientists especially bacteriologists who could find certain cells especially lymphocytes to play a major role in immune response.   The fact that the blood also contains soluble protective substances both heat stable which were later known as antibody and heat labile, later called as the complement system. These two were regarded as totally separate phenomenon in the beginning years. Eventually the distinctions between specific and non-specific responses were understood.   There are two types of immunity     i)    Non-specific (Innate, natural or native) immunity     ii)    Specific (Acquired) immunity.

I. IMMUNOLOGY OF MALE REPRODUCTIVE SYSTEM There are two basic functions of the immune surveillance of man and animals with respect to sperm immunity during spermatogenesis and fertilization process: support of the elimination of the vast majority of 'waste "spermatozoa that fail to fertilize and preservation of the tiny minority of surviving spermatozoa that are able to fertilize the oocytes. The primordial forms of spermatozoa arising in the seminiferous tubules of testes are preserved by the blood-testes barrier which is formed by sertoli cells ringing the semineferous tubules (Hunter, 1989). During maturation in the epidydimis, the spermatozoa acquire their antigenic properties. Simultaneously, the spermatozoa are coated with some proteins of seminal plasma having the immunosuppressive activity toward lymphocytes and macrophages involved in the immune reactions. The seminal plasma proteins accompany the migration of spermatozoa to the female genital tract (Matousek, 1985).

To an immunologist, the presence of embryo inside the mother’s uterus is perhaps one of the most surprising things. Pregnancy is a unique event in which a genetically and immunologically foreign foetus usually survives to full term without apparent rejection by the mother’s immune system. Thus, Pregnancy represents the unique physiological phenomenon of the symbiosis of two semi-allogeneic individuals: the mother and her fetus. Such symbiosis requires a sophisticated immunological regulation to avoid rejection-like reactions and to control the invasion of foreign foetal tissue into the maternal deciduas. A very fine tuning of cellular interactions at the interface of both individuals is indispensible for successful implantation and pregnancy. Over the past decade, more information has been gathered to provide insight into the complex immunological mechanisms that allow the foetus to grow and survive in most cases.

Immunological Causes of Male Infertility Immune mediated male infertility is an auto-immune disease.Spermatozoa are first produced at puberty and isolated from the systemic circulation by a structural barrier maintained by Sertoli cell tight junctions within the testis and the uninterrupted epithelial cell lining of the excurrent ductal system. Sperm production occurs well after the development of immunological tolerance to self antigens; therefore sperm specific components are viewed as foreign by the immune system. Whether spermatogonia, the primordial cell in spermatozoa differentiation, is also antigenically foreign is not established. What is known , is that immunization with sperm elicits a highly reproducible immune response that can impair fertility. Antisperm antibodies are found in about 10-15% of infertile men. Immunity only to those antigens present on the surface of viable, motile sperm will impair fertility. Antibodies to internal sperm antigens, due to an immune response to sperm degraded in the genital tract or to cross reacting microbial antibodies present in the sera of many fertile individuals , are of questionable relevance to infertility. A number of spermatozoa antigens have been identified .

In animals with a long gestation period, such as domestic animals, the acquired immune system is fully developed at birth, but cannot function at full adult levels for several weeks. The complete development of the acquired immunity depends on antigenic stimulation. The proper development of B cells and B cell antigen receptor (BCR) diversity requires clonal selection and antigen driven cell multiplication. Thus, the newborn animals are vulnerable to infection for the first few weeks of life. Hence, the temporary assistance in defending themselves at this time is provided by the mother in the form of antibodies and possibly T cells.   Development of the Immune System The thymus is first lymphoid organ to develop, followed closely by the secondary lymphoid organs. B cells appear soon after the development of spleen and  lymph nodes, but antibodies are not usually found until late in foetal life, if at all. The ability of fetus to respond to antigens develops very rapidly after the lymphoid organs appear, but all antigens are not equally capable of stimulating fetal lymphoid tissue. The immune system in a series of steps, each step permitting the foetus to respond to more antigens. These steps are driven by a gradual increase in the use of gene conversion or somatic mutation to antibody diversity. The ability to mount cell mediated immune (CMI) responses develops at the time as antibody production. Data from humans suggest that T cell receptor diversity is limited in the fetus and neonate and that cytokine production may be low. This may simply be due to their lack of to foreign antigens.

The history of the pregnancy test is a meaningful history embedded in magic, myth, politics, and science. From ancient Egyptian to modern times, the pregnancy test holds a cultural omnipresence that forces women to confront their fertility, femininity, and their future. Today we know that a pregnancy test that detects the human hormone known as human chorionic gonadatropin (hCG) offers the quickest and most accurate result for determining pregnancy. HCG is secreted by the placenta after the fertilized egg implants in the uterus and can be detected in both urine and blood. Urine pregnancy tests are convenient for home use, but a doctor may also opt to test blood as it provides a quantitative hCG number. Both methods are highly accurate and common. Pregnancy tests, however, were not always so accurate or so culturally accepted.   The diagnosis of pregnancy requires a multifaceted approach using three main diagnostic tools. These are (a) history and physical examination, (b)laboratory evaluation, and (c) ultrasonography. Currently, physicians may use all of these tools to diagnose pregnancy at early gestation and to help rule out other pathologies.

Overpopulation in humans and street dogs to some extent is a global problem of significant magnitude, with grave implications for the future. The overpopulation of dogs and cats is becoming an increasing concern in most countries of the world. As the global human population explodes so to do the staggering numbers of many best friends. Not only does this overpopulation cause millions of deaths each year and immeasurable levels of suffering in unwanted animals, these animals can cause significant risks to human health. Stray animals particularly dogs are source of dreaded diseases like rabies and other zoonoses, resulting in thousands of deaths annually. The management of wild and domestic animal population is step towards controlling the situation and fertility control techniques play a role in this. However, such technology is still in its infancy is yet to be used on a large scale. Advancements made in immunology and improved methods for the isolation of antigens specific reproductive system have paved the way for the development of antifertility vaccines in the past two decades. These vaccines are generally based on their ability block an indispensable step in the reproductive process.

The concept of immunonutrition has been developed in humans and animals mainly in relation to its impact on reinforcement of the immune system and its ability to resist disease. However, in the case of immunology of reproduction, different (even opposite) mechanisms  of immune system modulation are likely to be involved since the main objective is a local inhibition or the attenuation of the immune system toward the protection of the embryos. Most of the studies investigating the role of feeding and /or specific nutrients have used nutrient deficiency models to identify the mechanisms involved. During recent years, an increasing number of substrates have been recognized for their immunomodulating function. Macro and micronutrients have been identified as so-called immunonutrients. Although informative, such an approach might not apply to a concept of immunonutrition for reproduction when the dietary levels of a given nutrient will have to cover both the metabolic and immunomodulation needs for optimal reproduction.

The term transgenic animal refers to an animal in which there has been a deliberate modification of the genome - the material responsible for inherited characteristics - in contrast to spontaneous mutation (FELASA September 1992, revised February 1995). Foreign DNA is introduced into the animal, using recombinant DNA technology, and then must be transmitted through the germ line so that every cell, including germ cells, of the animal contain the same modified genetic material.  By simple means a transgenic animal is an animal in which foreign DNA has been incorporated into its original DNA. Transgenic animals are altered so that their DNA produces chemicals that normally they would not produce.

Embryo Transfer (ET) refers to the technique by which embryos are collected from the reproductive tract of female (donor) and transferred to that of another female (recipient) which carries it to term. The donor and recipient female are in same stage of estrous cycle. The main objective of ET is the improvement of animal population through maximum utilization of superior females and males. It allows faster progeny testing of both male and females. By obtaining and transferring embryos from pre-pubertal females shorten the generation interval from birth to reproductive age. The superior buffaloes will be sent for slaughter after getting lactation yield in metropolitan cities. Utilizing oocytes for In-vitro maturation (IVM) and In-vitro fertilization (IVF) from such slaughtered superior buffaloes can prevent wastage of genetic material. ET allows preservation of rare and extinct species and breeds of animal. ET can be used as a basic tool for twinning, cloning, sexing and to test chromosomal aberrations.

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