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OS 214: Excretory System Dr.

Dennis Serrano

Organ Transplantation, Immunology and Rejection Exam #2

meron pang donor na nagmatch ung HLA-A at HLA-


OUTLINE
B, un pa ring may match ng HLA-DR ang pipiliin).
I. Intoduction to Organ
Transplantation Cross-matching
II. Intoduction to Transplant
• A test for identification of antibody in the serum of
Immunology and Rejection
potential recipients which reacts directly with the
PART 1. lymphocytes or other cells of a potential donor
• A positive crossmatch is an absolute contraindication
Six organs maybe transplanted: to transplantation
• Kidney Other Considerations
• Heart • Patient’s immune status (no transplants for AIDS
• Pancreas
patients)
• Lung
• Co-morbidities
• Liver
• Small intestine
What Leads to Rejection
• Recognition of foreign antigen (donor organ)
Development of Organ Transplantation
• Activation and proliferation of antigen specific
• Replacement of tissue with artificial parts.
lymphocyte
• Dates back several hundred years ago • Damage to donor organ by antibodies.
o Chinese drawing: heart being taken or replaced
o Cosmos and Damien (Patron Saints of What to do to prevent rejection
Transplantation) with angels in the background: • 1960s: whole body irradiation (not done today)
replacing a leg o Prevents acute rejection, but not delayed.
o 1950s: First successful transplant (kidney) on Patients body eventually recovers and
identical twins. manufactures antibodies.
• Sir then showed a picture of a healthy kidney with the • Drugs – immunosuppressants; anti-thymus globulins
ureter vein and artery resting on the iliac area. Sabi
o Human T lymphocytes in thymus injected into the
niya, hindi tinatanggal yung lumang kidneys pag
horse / rabbit
nagtratransplant, dinadagdagan yung kidney,
nilalagay ung bago sa iliac area. Thus, 3 na yung
o Antibodies against human T lymphocytes are
kidney nung pasyente :p developed
• Tapos picture naman ng kidney na nireject, nagging o Antibodies are injected to the recipient, where T
kulay violet na at ayon sa 2011, thrombosed na daw. lymphocytes of the recipient will be killed
• Organs are harvested en bloc from cadaver donors.
Organ Donation
Rules of Tissue Transfer • In some countries, brain dead = organ donor.
Blood Type • Here in the Philippines, there are donor cards. (Back
Donor Blood Type Recipient Blood Type Safety of driver’s license, etc)
O* non-O safe
Rh- Rh+ safe
Rh+ Rh- safe Brain Death Criteria
A non-A dangerous • Deep Coma
B non-B dangerous
AB** non-AB dangerous
• No breathing
*Universal Donor; **Universal Recipient • No movement (except DTRs)
• No brainstem reflexes
Human Leukocyte Antigen (HLA) o No papillary light reflex
• Gene found in chromosome 6 that is important in o No blinking
transplantation. o No eye movement
• There are 6 loci, but for organ transplantation, only o No grimacing
HLA-A, HLA-B, and HLA-DR matter. (we have 2 of o No gagging or coughing
each, therefore, 6 ang minamatch) • Body temp > 32.20C
• Blood type must match first before proceeding to HLA • A condition that can cause brain death must be
matching. established
• The number of matches/mismatches predict the • No depressant drugs in blood/ urine
probability of transplant success. *Bedside diagnosis; transplant surgeon cannot proclaim brain
o Best: 0 mismatch (6 match) death.
o Worst: 6 mismatch (0 match)
• However, pwede pa rin magtransplant kahit na 6 Criteria of Organ Donation
mismatch, mas-iiimmunosuppress lang. Compatibility* Maximal
Age
Organ tissue
• HLA-DR is most predictive of rejection (kung Limit ABO HLA Crossmatch
ischemia
nagmatch ang isang HLA-DR sa isang donor, kahit Cornea 65 - - - 72 hrs.
Kidney 65-70 + + + 72 hrs.
Pancreas 15-50 + + + Page 1 of
24 hrs. 2
March 17, 2009 | Tuesday Cielo  Co  Collantes  Concepcion
OS 214: Excretory System Dr. Dennis Serrano

Organ Transplantation, Immunology and Rejection Exam #2

Liver 65-75 +/- - - 18-24 hrs. cascade of immune reactions. Most immunosuppressive
Lung 50 + - +/- 6 hrs. drugs used to prevent rejection target the Th.
Heart 55-60 + - +/- 6 hrs.
*+, criterion; -, not a criterion

PART 2.
Classification of Rejection
1. Hyperacute
Histocompatibility
• In patients with pre-formed cytotoxic Ab
• Mutual tolerance between tissues that allows them to
• Within minutes to hours after transplant
be grafted effectively.
• In recent years, this has been prevented through
Pre-transplant Histocompatibility Testing pre-transplant tissue cross-matching
Blood Typing 2. Accelerated
• ABO Blood Group • Within days to weeks (~2-3 days)
Tissue Typing • Flu-like symptoms
• Major Histocompatibility Complex (MHC) Antigens
• Humoral and cellular components
• Glycoproteins on cell membranes
• Doesn’t respond to anti-rejection treatment
• Encoded by MHC genes in short arm of Chr 6 3. Acute
• 2 Classes: • With flu-like symptoms as well
o Class I: HLA-A, HLA-B, HLA-C
• Myalgia, malaise, fever, decrease in urine output,
o Class II: HLA-DP, HLA-DR, HLA-DQ
high creatinine, tender graft, HPN
Tissue Cross-matching
• Manifests weeks to months post-transplant
• Detects circulating PREFORMED cytotoxic antibodies
• There is graft swelling (local inflammation)
• Keyword here is PREFORMED • Tx: increase immunosuppression
o from previous blood transfusion 4. Chronic
o pregnancy (fetus is considered a foreign body)
• Gradual decline in kidney function
o from previous transplant (these patients are
• There is interstitial fibrosis
called “sensitized people”; their immune systems
• Continuous bombardment with focal inflammatory
have already been alerted before)
reactions slowly scars kidney tissue
Indirect Direct Allorecognition
• Manifests years after sugery
Allorecognition
Recipient Donor APC • Cannot be prevented (Kaya may lifespan ang
APC

Self-MHC Class II Ag AlloMHC Class II Ag


+
Allopeptide +
+
Co-stimulatory 2nd Co-stimulatory 2nd
Signal Signal
Th

(IL2, IL 3-6. calcineurin, IF, NFAT)

pCTL B-Cell Macrophage


NK Cells
+Alloantigen +Alloantigen

CTL Plasma Cell Delayed Type


Hypersensitivity
Cytotoxicity Alloantibody organ transplants. Pag bata ka natransplant,
most probably, you will need a second.)
Figure 2. Immunosuppressants and their targets
Complement Mediated ADCC
Damage
Figure 1. Antigen-Presenting Cells (APC), whether from
the recipient or from the donor, are needed to activate Th
release of cytokines, which would in turn, activate a Page 2 of 2
March 17, 2009 | Tuesday Cielo  Co  Collantes  Concepcion