Serology & Blood Genetics

Ab-Ag reactions can occur IN VITRO and can provide valuable diagnostic information about disease. They can be performed quickly and offer a high degree of specificity and sensitivity. In these cases, the antibodies (Ab) are named on the basis of their FUNCTIONAL activity.

PRECIPITATION REACTIONS - involve SOLUBLE Ag which react with IgM or IgG antibodies; the reaction causes large aggregates of molecules; the Ab are called PRECIPITINS

AGGLUTINATION REACTIONS - involve PARTICULATE (INSOLUBLE) Ag; they link together to form visible aggregates, process is called AGGLUTINATION; Ab involved are called AGGLUTININS; most obvious use is in blood typing reactions

NEUTRALIZATION REACTIONS - neutralize toxins produced by bacteria or viruses by binding surface receptors; Ab involved are called ANTITOXINS

COMPLEMENT FIXATION REACTIONS - if Ab are present in the blood stream against a specific Ag, then the Ab-Ag-Complement will bind together and Complement is used up or FIXED; if Ab are not present, The Ag-Complement complex will activate Complement and lyse RBC's; failure to bring about lysis of RBC's in an indicator system is a POSITIVE TEST (indicates that Ab are present and host either has the pathogen in its system or has been exposed to the pathogen in question at some other time)

Hypersensitivity implies sensitivity beyond what is considered normal; the term is often used synonymously with ALLERGY. Previously contacted or SENSITIZED cells of the immune system react rapidly when contacted again by the same Ag (lots of Memory cells available) and in a manner which leads to tissue damage in the host (various lymphokinetic substances released). Hypersensitivity reactions are classified as IMMEDIATE or DELAYED and are of four principal types.

TYPE I (ANAPHYLAXIS) - involves IgE Ab and MAST cells or BASOPHILS; when MAST cell is bound by IgE Ab the cells become sensitized and when the Ag binds with the Ab the Mast cells DEGRANULATE releasing a series of chemical mediators; included in this group are Histamine, Heparin, Serotonin, Leukotrienes, and Prostaglandins; if action of these mediators causes a rapid reaction, then SHOCK (rapid fluid volume loss) is the end result

TYPE II (CYTOTOXIC) - IgG or IgM Ab react with Ag and Complement; lysis of tissue may occur; phagocytic cells may be attracted and engulf tissue cells or release chemicals toxic to host's cells

TYPE III (IMMUNE COMPLEX) - IgM or IgG Ab react with Ag and Complement to form complexes normally removed by phagocytosis; when large amounts of Ab are present, soluble complexes form that are not fixed by complement; these complexes circulate until they become lodged outside of the circulatory systemand become fixed by Complement and cause inflammatory reactions; as more Ag become available they elicit more Ab response and thus the inflammatory reaction may become severe and possibly deadly, dependent upon the part of the body in which the inflammation occurs

TYPE IV (CELL-MEDIATED) - involve mainly T cells and sometimes macrophages; Ab bound to tissue cells are phagocytized by macrophages; these come into contact with T cells which form clones in response to the contact; Lymphokines are then released and further contact with the Ag will cause damage directly to the host cell or phagocytosis of those cells by sensitized or activated macrophages; usually a DELAYED type of reaction

T cells are reponsible for surveillance of any foreign cells and thus are responsible for rejection of transplants or grafts which do not have the appropriate protein code on their surface membrane. Certain PRIVILEGED TISSUES do not cause an immune response on the part of the immune system or cause only a minor one.
(Note:"Unraveling Immune Privilege" Science Magazine, November 17, 1995)

AUTOGRAFT - a graft taken from one site on a person and transplanted to another site on that same person; no immune response

ISOGRAFT - grafts between identical twins; normally no immune response

ALLOGRAFT - graft between members of the same species but not identical twins; degree of immune response depends on closeness of match of protein code on cell surface

XENOGRAFT - grafts between different species; low degree of success; require much immunosuppressive technique and used only as last alternative until another organ from the same species can be found

CYCLOSPORINE - immunosuppressive drug which suppresses T-cell division; seems to prevent synthesis of Interleukin-2, a growth factor produced by helper T cells; allows humoral immunity to remain essentially intact and thus has increased success rate of Allografts

FK-456 - new drug, not yet approved for all uses by FDA

A new drug developed from soil samples from Easter Island has given new hope for improved chances of complication-free survival for organ transplant patients. Called Rapamune, (Wyeth-Ayerst), the finding were mentioned at the July 1998 meeting of the 17th world congress of the Transplantation society in Montreal.

TRANSFUSION REACTIONS AND Rh INCOMPATIBILITY

In 1900, Landsteiner discovered the A, B, and O blood types. In 1902, von Decastello and Sturli discovered type AB. In 1937, Landsteiner and Weiner discovered the Rh factor. Since those times at least fifteen other blood group systems have been discovered. Some of the other groups are universal and some are restricted to certain ethnic, cultural, or religious groups. They are often the result of inbreeding or strong beliefs about marriage partners within a closed societal grouping.

For example, the MN group was discovered by Landsteiner and Levine in 1927. All individuals have M, N, or MN antigens. Transfusion reactions are rare with this antigen, but it has been useful in medicolegal situations such as paternity suits.

Red blood cells contain Ag on their surface which are capable of inducing Ab reactions. The antigenic determinants of the A and B antigens are carbohydrates. These same carbohydrates are found in common foods and thus individuals have developed antibodies against either type A, type B, or type AB.

Individuals with type A blood contain Ab against type B, those with type B have Ab against type A, and individuals with type O blood have antibodies against type A, type B, and type AB. Type O individuals have neither antigen A nor antigen B on the surface of their red blood cells. Type AB individuals have no Ab against antigen A nor antigen B.

Humans possess Ab which react with RBC's from individuals of different blood groups. The immunoglobulins are called ISOHEMAGGLUTININS and ISOHEMOLYSINS. The lysis occurs as a consequence of isohemolysisn sensitizing the RBC's and making them vulnerable to the hemolytic action of Complement.

Blood type inheritance seems to be a CO-DOMINANCE situation: also known as multiple allelic inheritance.

Type A can donate to :A, AB can receive from A, O

Type B can donate to :B, AB can receive from B, O

Type AB can donate to :AB can receive from A, B, AB, O

Type O can donate to :A, B, AB, O can receive from O

In terms of RBC type only, O is sometimes considered the universal donor and AB the universal recipient; there are too many additional factors and variables to use this as an absolute standard

The Rh antigen appears to be possessed by more than 3/4 of the population and seems to follow Mendel's Law of Dominance

An Rh- individual can donate to Rh+ or Rh- individuals. If an Rh- person receives Rh+ blood he becomes sensitized and Ab are formed against the Rh antigen. Subsequent exposure to Rh+ blood will bring about a rapid hemolytic reaction.

Hemolytic Disease of the Newborn - Erythroblastosis fetalis

If an Rh- mother is carrying an Rh+ child the possibility exists for this condition to develop. Any RBC's from the baby which reach the maternal circulation, as the result of trauma, injury, tearing of blood vessels, or birth will sensitize the mother to the Rh antigen. Additional pregnancies are at risk since Ab against Rh antigen (Rh+) can cross the placental barrier and destroy developing RBC's (erythroblasts). Toxic products of destroyed RBC's can lead to jaundice of the baby and severe anemia. These babies are sometimes called "blue babies" because they lack sufficient RBC's to carry oxygenated blood. They are often yellow at birth as the result of the jaundice.

Present day treatment of this condition involves genetic counseling of prospective parents to alert them of the potential problem and the administration of RhoGam within 72 hours of the birth of each child (it may also be given during the pregnancy). RhoGam is a form of passive immunization and the mother receives Ab against the Rh antigen. This prevents the mother from developing a large concentration or titer of her own Ab against the Rh antigen and thus reduces the risk of hemolysis of the fetus' RBC's during any subsequent pregnancies.

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Email: demmelut@ps.fmcc.suny.edu