Chapter 35: Blood Types; Transfusion; Tissue and Organ Transplantation

Written By: Razaullah Khattak (DPT Medical Professional)

Student Source Reference: Guyton and Hall Textbook of Medical Physiology

Chapter: 35

To read more check out Chapter 18:

https://mednotesbyrazaullah.blogspot.com/2026/08/chapter-18-nervous-regulation-of.html

Antigenicity Causes 
Immune Reactions 
of Blood

When early blood transfusions were attempted between human beings, patients frequently experienced severe or fatal transfusion reactions. These dangerous reactions occur because human cell membranes contain specific surface proteins and polysaccharides that act as antigens. When foreign antigens enter a recipient’s bloodstream, plasma antibodies bind to them, triggering rapid cellular clumping, blood vessel obstruction, and immediate or delayed red blood cell destruction.

Understanding the complex antigen-antibody systems of human blood is vital for modern medical practice and clinical hematology. Blood compatibility relies primarily on two major antigenic systems: the O-A-B system and the Rh system. Proper blood typing, matching, and cross-matching prevent catastrophic hemolytic events, acute kidney shutdown, and neonatal conditions like erythroblastosis fetalis. These same immunological principles govern tissue and organ transplantation, where matching cellular antigens and managing graft rejection determine clinical success.

Antigenicity Causes Immune Reactions of Blood.

The human immune system recognizes foreign cell membrane markers and initiates aggressive defense mechanisms against mismatched blood cells.

Blood transfusions historically caused immediate or delayed reactions.

Mismatched transfusions often resulted in patient death.

Human blood cells contain distinct surface antigens.

Plasma antibodies react against foreign cell antigens.

Pre-transfusion testing determines blood antibody compatibility.

Human blood cells express over thirty common antigens.

Hundreds of rare blood cell antigens exist.

Most minor antigens cause weak immune responses.

Minor antigens help establish genetic parentage studies.

O-A-B system causes major transfusion reactions.

Rh system causes major transfusion reactions.

O-A-B Blood Types and Agglutinogens

The presence or absence of two specific surface carbohydrates determines an individual's primary blood group classification within the O-A-B system.

Type A and B antigens occur on red cells.

Red cell surface antigens are called agglutinogens.

Agglutinogens cause red blood cell clumping.

Individuals inherit zero, one, or both agglutinogens.

Four major blood types exist in humans.

Type O blood lacks both A and B agglutinogens.

• Type A blood contains only type A agglutinogen.
• Type B blood contains only type B agglutinogen.
• Type AB blood contains both A and B agglutinogens.

Genetic Determination of Agglutinogens

Blood group expression is governed by classical Mendelian genetics through combinations of three distinct alleles located on paired chromosomes.

• Two paired genes determine O-A-B blood type.
• Three gene alleles exist: O, A, and B.
• Type O gene is functionally inactive.
• Type O gene produces no significant agglutinogen.
• Type A gene produces strong A agglutinogen.
• Type B gene produces strong B agglutinogen.
• Six total genetic combinations (genotypes) exist.
• OO genotype produces type O blood.
• OA and AA genotypes produce type A blood.
• OB and BB genotypes produce type B blood.
• AB genotype produces type AB blood.
• Type O prevalence is approximately forty-seven percent.
• Type A prevalence is approximately forty-one percent.
• Type B prevalence is approximately nine percent.
• Type AB prevalence is approximately three percent.
• Type O and A genes occur most frequently.

Plasma Agglutinins and Their Origin

Plasma antibodies automatically develop against any major O-A-B agglutinogens that are absent from an individual's own red blood cell membranes.

• Missing red cell antigens cause agglutinin production.
• Absence of A antigen causes anti-A agglutinins.
• Absence of B antigen causes anti-B agglutinins.
• Type O plasma contains anti-A and anti-B.
• Type A plasma contains anti-B agglutinins.
• Type B plasma contains anti-A agglutinins.
• Type AB plasma contains no agglutinins.
• Infant plasma contains almost zero agglutinins at birth.
• Agglutinin production begins two to eight months post-birth.
• Peak agglutinin concentration occurs at age eight to ten.
• Agglutinin levels gradually decline in late life.
• Agglutinins are gamma globulin plasma proteins.
• Bone marrow and lymph tissues produce agglutinins.
• Agglutinins consist mainly of IgM and IgG molecules.
• Food and bacteria introduce small A and B antigens.
• Environmental antigen exposure initiates agglutinin formation.

Agglutination Process in Transfusion Reactions

When incompatible blood types mix, antibody binding bridges multiple red blood cells together, forming physical clumps that obstruct microcirculation.

• Mismatched plasma agglutinins attach to foreign red cells.
• IgG agglutinins have two antigen binding sites.
• IgM agglutinins have ten antigen binding sites.
• Single agglutinins bind multiple red blood cells simultaneously.
• Cellular bridging causes red blood cell clumping (agglutination).
• Clumped cells plug small systemic blood vessels.
• Physical distortion ruptures agglutinated cell membranes.
• Phagocytic white cells destroy agglutinated cell membranes.
• Hemoglobin release into plasma is called hemolysis.

Acute Hemolysis in Transfusion Reactions

In certain severe mismatched transfusions, immediate intravascular cell lysis occurs directly within the bloodstream rather than through delayed phagocytosis.

• Immediate intravascular hemolysis occurs in severe mismatches.
• Antibodies activate complement system protein cascade.
• Complement complex releases lytic enzymes.
• Lytic enzymes rupture cell membranes directly.
• Immediate lytic reactions require high antibody titers.
• IgM hemolysin antibodies primarily cause acute lysis.
• Immediate intravascular hemolysis is relatively rare.

Laboratory Blood Typing Procedure

Determining recipient and donor blood compatibility requires mixing isolated red blood cells with known antibody sera to observe cellular clumping.

• Blood typing precedes all clinical blood transfusions.
• Red cells separate from plasma using saline dilution.
• Saline-diluted cells mix with anti-A agglutinins.
• Saline-diluted cells mix with anti-B agglutinins.
• Microscopic observation checks for cellular clumping.
• Clumping indicates positive antigen-antibody reactions.
• Type O cells show zero agglutination.
• Type A cells agglutinate with anti-A serum.
• Type B cells agglutinate with anti-B serum.

Type AB cells agglutinate with both sera.

Rh Blood Types and Antigens

Unlike the spontaneous occurrence of O-A-B agglutinins, antibody development within the Rh system requires significant prior exposure to foreign Rh antigens.

• Rh system causes major blood transfusion reactions.
• Rh agglutinins rarely form spontaneously in plasma.
• Rh sensitization requires massive foreign Rh antigen exposure.
• Six common Rh antigen factors exist: C, D, E, c, d, e.
• Individuals inherit one factor from each gene pair.
• Type D antigen is overwhelmingly prevalent and antigenic.
• Presence of D antigen defines Rh-positive status.
• Absence of D antigen defines Rh-negative status.
• Eighty-five percent of white individuals are Rh-positive.
• Ninety-five percent of American Black individuals are Rh-positive.
• Nearly one hundred percent of African Black individuals are Rh-positive.

Rh Immune Response and Transfusion Reactions

Injecting Rh-positive red cells into an Rh-negative recipient triggers a slow primary immune response that develops anti-Rh antibodies over several months.

• Foreign Rh injection stimulates anti-Rh agglutinin production.
• Maximum anti-Rh antibody concentrations require two to four months.
• Multiple Rh exposures produce strong recipient sensitization.
• First exposure to Rh-positive blood causes no immediate reaction.
• Anti-Rh antibodies develop slowly over subsequent weeks.
• Macrophages hemolyze circulating foreign Rh-positive cells.
• Initial exposure creates mild delayed transfusion reactions.
• Subsequent Rh-positive transfusions trigger immediate severe reactions.

Erythroblastosis Fetalis Pathophysiology

Hemolytic disease of the newborn occurs when an Rh-negative mother develops antibodies against an Rh-positive fetus, leading to intra-uterine cell destruction.

• Erythroblastosis fetalis affects fetuses and newborns.
• Disease involves maternal agglutination of fetal red cells.
• Occurs typically with Rh-negative mother and Rh-positive father.
• Fetus inherits Rh-positive antigen from father.
• Mother develops anti-Rh agglutinins against fetal cells.
• Maternal agglutinins diffuse across placental membrane.
• First Rh-positive pregnancy rarely causes infant harm.
• Three percent of second Rh-positive babies show disease.
• Ten percent of third Rh-positive babies show disease.
• Disease incidence rises progressively with subsequent pregnancies.

Clinical Effects of Fetal Antibodies

Maternal antibodies entering fetal circulation cause widespread hemolysis, resulting in severe fetal anemia, jaundice, hepatosplenomegaly, and potential neurological damage.

• Maternal antibodies cause intravascular fetal cell agglutination.
• Hemolyzed fetal red cells release free hemoglobin.
• Fetal macrophages convert free hemoglobin into bilirubin.
• Accumulated bilirubin turns newborn skin yellow (jaundice).
• Erythroblastotic infants exhibit severe anemia at birth.
• Maternal anti-Rh agglutinins circulate for one to two months.
• Fetal liver and spleen enlarge to produce replacement red cells.
• Rapid hemopoiesis releases early nucleated blastic red cells.
• Nucleated blastic red cells give disease its name.
• Severe anemia represents primary cause of infant death.
• Bilirubin precipitation in brain cells causes neuronal destruction.
• Motor area neuronal damage from bilirubin is called kernicterus.

Neonatal Treatment and Disease Prevention

Managing erythroblastotic infants involves exchange transfusions to eliminate bilirubin, while administering maternal anti-D antibodies prevents initial maternal sensitization.

Treatment replaces newborn blood with Rh-negative blood.

• Four hundred milliliters of Rh-negative blood is infused slowly.
• Exchange transfusion removes newborn's Rh-positive cells.
• Repeated transfusions keep bilirubin low to prevent kernicterus.
• Transfused Rh-negative cells last six or more weeks.
• Maternal anti-Rh agglutinins naturally destroy over time.
• Administering Rh immunoglobulin globin prevents mother's sensitization.
• Anti-D antibody administration begins at twenty-eight to thirty weeks.
• Anti-D antibody given post-delivery prevents D-antigen sensitization.
• Anti-D antibody inhibits maternal antigen-induced B-cell activation.
• Administered antibodies bind fetal cell D-antigen sites directly.

Mechanisms of Transfusion Reactions

Transfusing mismatched blood leads to recipient antibody attacks on donor red cells, while donor antibodies become too diluted to affect recipient tissues.

• Recipient antibodies agglutinate small volumes of donor blood.
• Injected donor plasma dilutes rapidly within recipient circulation.
• Diluted donor agglutinins rarely cause recipient cell clumping.
• Recipient agglutinins maintain high titers against donor cells.
• Hemolyzed red cell phagocytosis generates systemic bilirubin.
• Liver excretes generated bilirubin into bile through intestines.
• Jaundice requires hemolyzing over four hundred milliliters of blood daily.

Acute Kidney Shutdown After Transfusion

Renal failure represents one of the most dangerous complications of severe transfusion reactions, resulting from vascular constriction, circulatory shock, and tubular blockage.

• Transfusion reactions can trigger acute kidney shutdown.
• Renal failure begins within minutes to hours post-transfusion.
• Antigen-antibody reactions release toxic systemic vasoconstrictors.
• Severe renal vasoconstriction drastically reduces kidney blood flow.
• Red cell loss and circulating toxins trigger circulatory shock.
• Severe arterial blood pressure drops reduce urine output.
• Unbound free hemoglobin filters through glomerular membranes.
• Haptoglobin plasma protein binds small quantities of hemoglobin.
• Excess unabsorbed tubular hemoglobin precipitates inside tubules.
• Precipitated hemoglobin blocks physical passage inside kidney tubules.
• Vasoconstriction, shock, and tubular blockage cause renal shutdown.
• Complete untreated renal shutdown causes death within seven to twelve days.

Tissue and Organ Transplantation Types

Graft rejection is driven by cell-surface tissue antigens that stimulate host immune defenses, classifying transplants based on the genetic relationship between donor and recipient.

• Tissue cells contain surface antigens similar to red blood cells.
• Recipient immune systems resist foreign transplanted tissue cells.
• Autograft transfers tissue within same individual's body.
• Isograft transfers tissue between genetically identical twins.
• Allograft transfers tissue between different individuals of same species.
• Xenograft transfers tissue between different biological species.
• Autografts and isografts survive indefinitely with adequate blood supply.
• Xenografts trigger severe rejection within one day to five weeks.
• Skin, kidney, heart, liver, bone marrow, and lung allografts exist.
• Kidney allografts can survive five to fifteen years.
• Heart and liver allografts can survive one to fifteen years.

Tissue Typing and HLA Antigens

Successful allograft transplantation relies on matching human leukocyte antigens (HLA) to minimize post-transplant cellular immune responses and graft destruction.

• Human Leukocyte Antigens (HLA) cause primary graft rejection.
• Six specific HLA antigens exist on each person's cell membranes.
• Over one hundred fifty different HLA antigens exist overall.
• More than one trillion possible HLA genetic combinations exist.
• Identical twins share identical HLA cellular antigens.
• Lymphocyte membrane testing determines recipient HLA antigen types.
• Separated lymphocytes mix with specific antisera and complement.
• Trans-membrane dye uptake testing measures lymphocytic membrane damage.
• Close HLA matching significantly reduces allograft rejection risks.
• Best non-twin matches occur between siblings or parents and children.

Immunosuppressive Therapy for Transplants

Suppressing host T-lymphocyte function prevents cellular rejection of transplanted organs, though it simultaneously increases patient vulnerability to infections and malignancy.

• Total immune suppression completely prevents organ graft rejection.
• T-cell suppression is critical for preventing cellular graft rejection.
• Glucocorticoid hormones suppress growth of overall lymphoid tissues.
• Glucocorticoids decrease formation of circulating antibodies and T cells.
• Azathioprine exerts toxic effects on lymphoid tissue formation.
• Cyclosporine specifically inhibits helper T-cell activation and formation.
• Cyclosporine blocks T-cell rejection without depressing all immunity.
• Immunosuppressed patients face high risks of rampant infectious diseases.
• Immunosuppression increases overall cancer incidence several-fold.
• Immune systems normally destroy early proliferating cancer cells.
• Modern therapy balances rejection prevention with drug toxicity moderation.

Disclaimer: This content is for educational purposes only and not a substitute for professional medical advice.