PHYSIOLOGY d.

) Epitope/Antigenic determinant that portion of

Christopher De Guzman, MD antigen that combines with the products of a
specific immune response.
IMMUNOLOGY UNIT
TYPES OF GRAFT
OUTLINE
1. ALLOGRAFT same type, eg one human kidney
I. Tissue Organ Transplantation to another
II. Blood Groups and Blood Transfusion - Kidney transplant: highest probability of survival
III. Resistance of the Body to Infection - Statistics of orphan donation
IV. Immunity and allergy KIDNEY 98% (dead)
95%(live)
LIVER 85-90% success rate
I. TISSUE ORGAN AND HEART 83%
2. ISOGRAFT and AUTOGRAFT
TRANSPLANTATION - Transplant contain virtually same type of antigen
Heart Transplant as the tissue of the recipient
- Transplant live normally and indefinitely if or with
- First administered by Dr. Christian Barnard adequate blood supply.
- Baboon- human
- Mismatched, unsuccessful. 3.XENOGRAFT
- Immune reactions almost always occur
ANTIGEN-ANTIBODY INTERACTION - Death of all cells
Antigen are widely present in other cells of the Kidney allograft 10 to 15 years
body. Autograft liver and heart transplant 1-15 years
Any foreign cell transplanted anywhere in the Age is a huge factor as older persons have
body of a recipient can produce an immune concomitant disease (co-existing diseases) that
reaction. might compromise the organ transplantation.
Main obstacle: rejection of the foreign Transplatation to replace diseased/defective tisse
tissue by the host - In dead donors : cornea and heart
Increase in foreign antigen on the donor - In live donors: in paired/large/generating organ or
organ, the more rapid and severe the rejection tissues such as skin, bowel, lung, liver, blood
reaction
Live Donor
TRANSPLANTATION OF CELLULAR TISSUES In transplanting complex organs (but not small
tissue grafts), the large blood vessels of the
ANTIGENS
organs are surgically connected to those of the
a.) Immunogen substance that induce a specific recipient
response. Non cellular tissues: titanium
b.) Antigen (Ag) reacts with the products of a Provide nonliving structural support within which
specific immune response. the recipient; living cells become established.
c.) Hapten non immunogenic by themselves; can Artificial bone (prosthesis) do not produce an
induce an immune response when coupled to a antigenic substance.
carrier molecule. Corneal transplants have high success rates
because fewer blood vessels in the cornea enter
 the hosts systems to stimulate in immune - T cells are mainly the portion of the immune
reaction. system important for killing the cells of the graft,
Bone marrow transplant bring their own immune hence, also named T-reg cells.
system with them.
Newer implants use non rusting titanium joints Human T - Lymphocytes
with the midsection of bone composed of light
weight polyethylene.
Organ transplants from anumals to humans are
subject to hyperacute allergic reactions.

HUMAN LEUKOCYTE ANTIGEN (HLA)

- Important antigen for causing graft rejection.

- Six (6) present in each cell membrane of each IMMUNOSUPPRESSIVE AGENTS
person
- Trillon possible combinations 1. Glucocorticoid
- Found in lymphocytes and other tissue cells. hormones isolated from the adrenal cortex;
- Virtually impossible except in identical twins to suppress growth of all lymphoid tissue;
haee the same 6 HLA. decrease formation of both antibodies and T
cells
Tissue Typing separation of the antigens from the Best choice but has side effects
lymphocyte. Pinples, moonface, hypertension, bone
Lymphocytes are mixed with appropriate fracture, case noid face
antigen and complement. 2. Azathiopine
After incubation, the cell are treated for membrane Drugs that have a toxic effect on the
damage. lymphoid system
Postive when there is an uptake by lymphocyte Blocks the formation of antibodies and T
cells.
Some antigens are not severely antigenic, therefore it
3. Cyclosporine
allows graft acceptance.
Specific inhibitory effect of the formation
Obtain the best possible match between donor and
of T helper cells
recipient.
Effective in blocking the t cell rejection
Best matches are between siblings and between
reaction.
parent and child.
Most valuable tool of all the drug
Identical twins almost have no rejection.
because it does not depress some parts
PREVENTION OF GRAFT REJECTION of the immune system.
BYSUPPRESSING the IMMUNE SYSTEM 4. Tacrolimus block in cytokine production; side
effects are similar to cyclosporine
- Complete rejection: no graft rejection 5. Sirolimus side effects include
- Even with best possible tissue typing, allograft thrombocytopenia and hyeperlipidemia
still need a specific therapy to suppress the 6. Microphenolate
immune system.
Complication of the Immunosuppression

- Steroids depress the immune system

 1. Infection opportunistic pathogens 1. Transplantation of living tissues in human beings
2. Cancer immune system is important in have very limited but important success
destroying many early cancer cells (T killer cells) 2. Research continue to study various ways to fool
before they begin to proliferate. the immune system.

SUMMARY OF CONCEPTS

II. BLOOD GROUPS AND BLOOD O Universal donor; no recipient to recognize any
agglutinogen; can donate to all recipients because their cells
TRANSFUSION are not recognized by any ABO agglutinins.
Blood of different people has different antigenic properties.
Titers of Agglutinins at Different Ages
Antibodies in the plasma of one blood react with the
antigen on the surface of the RBC of another blood. At birth, no agglutinins in the plasma
2 8 months, after birth, infants begin to produce
BLOOD SYSTEMS
agglutinins.
1. O-A-B systems People usually have antibodies/agglutinogens against
2. Rh system those red cells antigen that they lack
3. Duffy, Kidd, Kell System Maximum rate reached at 8-10 years of age.
Decline in titers throughout throughout the remaining
1. ABO system years.
- Discovered in the 1900s
Origin of Agglutinins in the Plasma
- Most important in assuring SAFE blood transfusion.
A antigen (agglutinogen) - Agglutinins = gamma globulins=antibodies
B antigen (agglutinogen) - Y shaped
- Most are IgM and IgG molecules
Agglutinogen antigen causing blood cells to agglutinate - Small amounts of Group A and Group B antigens
which causes most blood transfusion. enter the body in food, bacteria and in other way
- Inherited which initiate development of anti A and anti B
Relative Frequencies agglutinins.
Blood Type Frequency BLOOD TYPING before giving blood transfusion, determine
O 47% the blood type of the recipients blood and the blood type of the
A 42% donors blood.
B 9%
AB 3% Procedure for Blood Typing
1. Separation of red blood cells from plasma and dilution
with saline.
Genetic Determinants of Agglutinogens
2. One portion mixed with anti-A agglutinin and another
- 2 genes, one on each of the 2 paired chromosomes portion mixed with anti B agglutinin
- Types A and B gene cases strong agglutination on 3. After several minutes, mixtures are observed under
the cells the microscope.
- Type O gene is functionless 4. Note for clumping/agglutination; an antigen-antibody
reaction read as (+)
Take note:
Red Blood Cell Type Anti A Anti B
AB as a universal recipient; they do not have A or B agglutinins O - -
against any ABO phenotype. A + -
B - +
AB + +

2. Rh System
Named for the Rhesus monkey in which they
were first discovered.
Importance in human health is to avoid the
danger of Rh incompatibility between the
mother and the fetus.
2nd most important pre transfusion setting
Differences between Rh and ABO Systems
1. In ABO systems, plasma agglutinins responsible for
causing transfusion reaction develops rapidly; In Rh
systems, spontaneous agglutination almost never
occur.
2. In Rh systems, a person must first be massively
exposed to the Rh antigen by transfusion of blood
containing the antigen, before agglutination occurs.
Rh Antigen (Rh Positive and Rh-Negative)
- When multiple exposure -> Rh(-) person becomes strongly
sensitized.
Incidence of the Disease
If the mother is Rh (-), and the father is
Rh(+), the following may occur:
a. 1st born Rh(+) no harm
b. 2nd child Rh (+) 3% harm
c. 3rd child Rh (+) 10% harm
Effect of Mothers Antibodies on the Fetus
Anti Rh antibodies formed in the mother diffuse through
the placental membranes in to the fetus blood
Aggluntination of the fetus blood
Agglutinated RBC hemolyze
Release Hb into the blood
Fetus macrophage convert Hb into bilirubin causing
jaundice
Rh antibodies can attack and damage other cells of the
body

Six Common Types of Rh Antigen Erythroblastosis Fetalis = Hemolytic Disease

1. C Disease of the fetus and the newborn child characterized

2. D by agglutination and phagocytosis of the fetus RBC
3. E Usually, mother is Rh (-) and father is Rh (+)
4. c Baby inherited the Rh (+) antigen from the father and
5. d mother develops anti Rh agglutinins from exposure to the
6. e babys Rh antigen
Micro hemorrhages during gestation permit fetal RBCs to
Rh Positivity enter maternal circulation
Sensitization of the mother against the Rh factor.
Rh positive indication = has D antigen Anti Rh agglutinins from the mother usually circulate in
Rh negative indication = no D antigen the infants blood for 1-2 months after birth
Massive hemolysis -> proliferation at nucleatic, blastic
Prevalence:
cells from the bone marrow into the circulatory system
A. White Exhibit permanent mental impairment or damage to
85% Rh positive another cells of the brain because of precipitation of
15 % Rh negative bilirubin in the neuronal cells (KERNICTERUS)
B. Black
Clinical Features of Erythrbolastosis Fetalis
95% Rh positive
100% Rh positive
1. Jaundice
Rh Sensitization
- Hemolysis
*Formation of Anti-Rh Agglutinins - RBC destroyed
- Bilirubin formed
- When Rh (+) blood injected into an Rh (-) person, anti Rh 2. Anemia at birth
agglutinins occurring 2-4 months later 3. Enlarged spleen and liver
Treatment of Erythroblastoic Neonate Complications of Hemolysis

- Replace the neonates blood wth Rh hepatic blood 1. Jaundice

- 400 mL of Rh negative blood infused over a period of - Whether acute or delayed, deposition of yellow bile
1.5/ more hours while the neonates own Rh positive pigment in the tissue
blood is being removed - Occurs when >400 mL of blood hemolyzed in less
- The process is repeated for several times during the than a day.
first few hours of life to prevent kernicterus. 2. Acute Renal failure

Treatment of the Sensitized Mother Ag-Ab complexes release toxic

substances from the hemolyzing blood
-Prevent formation of maternal anti Rh antibodies.

Injection of human immune globulin into the mother

within 72 hours after delivery (Rh immune-globulin Renal vasoconstriction
=RHIG) or Rhogam
Rhogam contains antibodies agains positive fetal
RBCs, destroying them before the maternal blood
reacts by producing its own antbodies. Circulatory shock

BLOOD TRANSFUSION

- Transfused blood must not contain red cells that the

Blood pressure falls
recipients antibodies can clump/
- Every blood transfusion should be regarded as a
possible threat to life.
Urine output decreases, total amount of free Hb
in the blood is greater than the quantity that can
bind with haptoglobin
TRANSFUSION REACTIONS

When there is a blood mismatch, the red cells leakage of haptoglobin into the
agglutinate as a result of the agglutinins attaching kidney tubules
themselves to the RBCs.
A single agglutinin can have affect two or more RBCs.
Agglutination or clumping plug small blood vessels
renal tubular blockage
in circulatory system destruction of agglutinated cells by
phagocytic WbC release HB in the plasma
HEMOLYSIS excreted into the bile by the liver
JAUNDICE.
ACUTE RENAL FAILURE
Acute Hemolysis

- Intermediate hemolysis of RBCs

- Less common than delayed hemolysis which results
from the phagocytosis of agglutinated cells.
- RBCs of the donor cells are agglutinated.
- Rare for transfused blood to cause agglutination of
the recipients RBC because plasma proteins of the
donors blood decreased titer of differed
agglutination.
Classification of Transfusion Reactions

Immune Type: Antigen-Antibody Reaction

Non Immune Type: No A anti interaction

I. Immune Type of Transfusion Reaction (Antigen-

Antibody Reaction)
1. Anti RB (hemolytic reaction)
2. Anti WBC manifested as febrile reactions
3. Anti Platelet
4. Anti IgE (esp IgA)
5. Hypersensitivity Reactions manifested as hives,
itching and anaphylaxis
6. Graft versus host disease (GVHD)
- Transfused lymphocytes engraft and multiply on
immunocompromised patients; newly engrafted
lymphocytes attack the host

II. NON-IMMUNE TYPE

1. Circulatory Overload in patients with compromised
cardiac/renal function.
2. Massive Transfusion causes dilutional
thrombocytopenia.
3. Transmission of Infection viral hepatitis, syphilis,
HIV, malaria, CMV
4. Air/Fat embolism
5. Thrombophlebitis
6. Potassium intoxication mainly due to stored blood;
cause cardiac arrest
7. Ammonia intoxication due to stored blood
8. Siderosis with long term blood transfusion in
repeated transfusion such as hemophilia and
thalassemia; manifests as liver cirrhosis or
hemachromatosis