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Polytechnic University of the Philippines

College of Science
Department of Biology

Antigen-Antibody Reaction: Pre-eclampsia/ Eclainpsia on


Human Pregnancy
By
Christine P. Alayon
[1]Students, Department of Biology, College of Science, Polytechnic University of the Philippines

Humans and all other living organisms in this world are all heavily exposed to vast array of toxic
or allergenic substances that threaten normal homeostasis causing them impairment and harm. Most
organisms guard themselves against such substances in different ways such as with physical barriers, or
with chemicals that repel or exterminate invaders. Each individual have these general protective
mechanisms, but they also have a more advanced protective system called the immune system. The
immune system is known as the body’s natural defense system, it protects the body from infection
through various lines of defense. The ability to distinguish things that belong in an individuals’ body from
foreign agents and infectious organisms is the basis of the entire immune system. The human immune
system is said to be the most complex among every other organisms. The defensive reaction of the
adaptive immune system is called the immune response. When foreign substances or molecules called
antigens enters the body, it stimulates the immune system to produce antibodies.
Antigens can be bacteria, viruses, or fungi that cause infection and disease. They can also be
substances such as toxics and enzymes, called allergens that bring on an allergic reaction. The major role
that antibodies play is to bind with antigens and inactivate them so that other bodily processes can take
over, destroy, and remove the foreign substances from the body.
Antibodies, also called immunoglobulins are defined as the proteins manufactured by the body
that recognize and neutralize any microbial toxin or foreign substance such as bacteria and viruses.
Antibody molecules are typically Y-shaped, with a binding site on each arm of the Y. In turn, the binding
sites of each antibody have a specific shape. Only antigens that match this shape will fit into them. Some
antigens may not induce antibody production, but instead creates immunological tolerance. An antigen
introduced into the body produces only specific antibodies and will react with only those specific
antigens. The B lymphocytes are known as the only cells that make antibodies. Mainly two forms of
antibodies exist. One those that are membrane-bound and act as receptor for antigens on the surface of B
lymphocytes and the other that are involved in inhibition of entry and spread of pathogens and are found
in blood circulation and connective tissues (Huston, 1997).
Antigen-Antibody reaction (Ag-Ab reaction) is known as the interactions between antigens and
antibodies. It is similar to that of enzyme substrate interaction except that this interaction does not lead to
irreversible alteration either in antibody or antigen and therefore reversible (Rao, 2002). These reactions
are said to be highly specific, and an antigen reacts only with antibodies produced by itself or with closely
related antigens. Antibodies recognize molecular shapes (epitopes) on antigens. Generally, the better the
fit of the epitope (in terms of both geometry and chemical character) to the antibody combining site, the
more favorable the interactions that will be formed between the antibody and antigen and the higher the
affinity of the antibody for antigen. One of the most important factors in determining antibody efficacy in
vivo is the affinity of the antibody for the antigen.
The human immune system is trained during the early postnatal period. The immune system of
men, will have the chance to contact sperm antigens at puberty when the sperm first emerge in the testis
and epididymis. Likewise, when women become sexually active, their immune system will predictably
contact sperm antigens. Therefore, once sperm, as an autoantigen (usually a normal protein or complex
of proteins that is recognized by the immune system of patients suffering from a specific autoimmune
disease) activates the human immune system, an autoimmune response against human sperm will occur.
The blood-testis barrier and the epididymal blood-epithelium barrier in humans are important structures in
preventing sperm antigens from contacting immunocompetent cells, due to the tight junctions of Sertoli
and epithelial cells. This creates favorable conditions for spermatogenesis and sperm survival in the
testicular fluid, and sperm maturation in the epididymal fluid. It also prevents the occurrence of
autoimmunity after puberty. Various protective mechanisms besides the blood-testis barrier and the
blood-epithelium barrier have also been identified. Immunosuppressive substances have been found in
semen and follicular fluid. Furthermore, suppressor T lymphocytes in the human immune system, which
partially mediate the normal state of immunologic unresponsiveness toward sperm autoantigens, also play
an important role in preventing the autoimmune response. In addition, the cervix is a site of sperm
filtration, and uterine fluid has significantly high concentrations of IgG and IgA, which lead to increased
phagocytosis of intact or defective sperm, and corrupted sperm debris. Moreover, components of seminal
plasma and polymorphonuclear neutrophils in semen could eliminate nonviable sperm or debris.
During maturation of spermatogenesis, new antigens are expressed on developing spermatocytes
and spermatids. When these antigens come into contact with immunocompetent cells, or spermatozoal
antigens are exposed to the mucosal and systemic immune systems. Developmental abnormalities of the
formation of the blood-testis barrier, traumatic disruption, infection or unilateral focal cryptic obstructions
could lead to immunogenic sperm antigens being exposed to the immune system thus initiating an
immune response to produce ASAs. In addition, in some cases, immunity to sperm cells may be the result
of altered sperm antigens. Sperm antibodies reduce fertility, but do not invariably prevent conception.
Rather, the effects are graduated, the less likely it is that a pregnancy will occur. Like any other kind of
antibody manufactured by the body, sperm antibodies are formed in response to antigens. These antigens
are proteins, which appear on the outer sperm membranes as the young sperm cells, develop within the
male testes. Antigens can only stimulate antibody production when they come in contact with components
of the blood. Under normal conditions, blood and sperm do not mix. Direct contact between the two is
prevented by a cellular structure in the testes called the blood/testis barrier. This barrier is formed by
Sertoli cells, which abut very closely against each other, forming tight junctions that separate the
developing sperm cells from the blood and prevent immunologic stimulation. However, the blood/testis
barrier can be broken by physical or chemical injury or by infection. When this barrier is breached, sperm
antigens escape from their immunologically protected environment and come in direct contact with blood
elements that launch an immunologic attack.
In the case of sexual intercourse, within the female’s body, deposited sperm are regarded as
foreign invader cells and as such would normally be targeted for attack and destruction by circulating
antibodies. Yet sperm, which are immunologic unknown to the woman, do not usually cause an antibody
response. Although usually exposed to billions of sperm during her lifetime, few women develop sperm
antibodies. The reason behind this process is not yet well understood. It is known that the cellular
construction of the vagina provides a physical barricade somewhat similar to the blood: testis barrier in
the male. Here, too, physical damage or infection will increase the likelihood of sperm and blood mixing
and subsequent antibody production.
Once sperm and blood come in contact, whether in the male or female, specific antibodies are
produced against them by specialized blood cells called T- and B-lymphocytes. The three main types of
sperm antibodies produced are Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin
M (IgM). These antibodies bind to the proteins (antigens) on the sperm head, midpiece or tail. The
antibodies formed may be of the circulatory type (in the blood serum) or secretory type (in the tissue).
This is important because high levels of antibodies in the blood do not always antibodies will find their
way to the semen where they can affect the sperm. For example, the concentration of IgG is much lower
in secretions of the reproductive tract that it is in the blood. Conversely, the local level of IgA is higher in
the reproductive secretions than in the blood.
Once sperm antibodies have formed, they can affect sperm in several different ways. Some
antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm
from swimming through the cervix (immobilizing antibodies). Antibodies can also block the sperm’s
ability to bind to the zona pellucida of the egg, a prerequisite for fertilization. Finally, there is evidence
that the fertilized egg shares some of the same antigens that are found on the sperm. It is possible that
sperm antibodies present in the mother can react with the early embryo, resulting in its destruction by
phagocytic cells. IgA is the most common antibody in secretions of the cervix, uterus and fallopian tubes.
IgG may also be present, but IgM is found only rarely. In the male, IgA and IgG are found in the semen
although there is controversy as to whether they originate locally (secreted by testicular cells) or cross
over from the circulation. Antibodies of the IgM class are not found in semen.
Pre-eclampsia/eclainpsia is a disorder of the second half of human pregnancy, and a principal
cause of both maternal and perinatal mortality and morbidity. Its cause is unknown and its investigation is
constrained by the lack of any equivalent disorder in other mammalian species. The diagnosis of pre-
eclampsia varies between different investigators, it may be a syndrome with several different aetiologies
rather than a single disease entity. Circulating immune (antigen-antibody) complexes have been proposed
as possibly important in the pathogenesis of pre-eclampsia. It is was reported by Knox et al. (1978) that
circulating immune complexes do not occur regularly in pre-eclampsia. the principal cause of
preeclampsia is still unkown. Although it is certain that the diseases relates to the presence of placental
tissue, the proximate cause is obscure.
Another study was also carried out on 26 pregnant women. Sixteen of those women suffered from
moderately manifested form of pre-eclampsia, but the remaining ten women had a normal course of
pregnancy. The age of women with pre-eclampsia was between 22 to 30 years, but that of the control
group--from 30 to 37 years. The women with pre-eclampsia were investigated between 28 to 35 weeks'
gestation and the women with normal pregnancy--between 30 to 37 weeks' gestation. Immunoglobulin A,
M, G were determined as well as transferrin and T and B lymphocytes. Immunoglobulin A was increased
in sera of women with pre-eclampsia, but there were no changes in other examined parameters. It is
possible that similar increase could be due to a reduced elimination of immunoglobulin A through the
hepatobiliary tract, which cause its elevation in its serum level. The proposed explanation could be
accepted as plausible, because there is impairment of liver function in women with preeclampsia. Future
studies are needed to prove this fact.
REFERENCES:

o G. Eric Knox,Sergio Stagno,John E. Volanakis,John F. Huddleston (1978). A search for


antigen-antibody complexes in pre-eclampsia: Further evidence against immunologic
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o Sjoberg AP, Trouw LA, Blom AM. Complement activation and inhibition: a delicate
balance. Trends Immunol. 2009;30:83–90. [PubMed]
o Landsteiner, K. and Levine, P.. On group specific substances in human spermatozoa.
Immunol 12:415, 1926.
o Huston DP. The biology of the immune system. JAMA. 1997;278:1804–1814.
o Burlingham WJ. A lesson in tolerance--maternal instruction to fetal cells. N Engl J Med.
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