Organ Transplantation, Immunology and Rejection
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OS 214: Excretory System
Dr. Dennis Serrano
Exam #2
Organ Transplantation, Immunology and Rejection
OUTLINE I. Intoduction to Organ Transplantation II. Intoduction to to Transplant
meron pang donor na nagmatch ung HLA-A at HLAB, un pa ring may match ng HLA-DR ang pipiliin). Cross-matching •
A test for identification of antibody in the serum of
potential recipients which reacts directly with the lymphocytes or other cells of a potential donor A positive crossmatch is an absolute contraindication to transplantation Other Considerations Patient’s immune status (no transplants for AIDS patients) Co-morbidities
PART 1.
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Six organs maybe transplanted: Kidney
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Heart
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Pancreas
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Lung
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Liver
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Small intestine
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What Leads to Rejection Recognition of foreign antigen (donor organ)
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Development of Organ Transplantation Transplantation •
Replacement of tissue with artificial parts.
•
Dates back several hundred years ago o o
o
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•
•
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Chinese drawing: heart being taken or replaced Cosmos and Damien (Patron Saints of Transplantation) with angels in the background: replacing a leg 1950s: First successful transplant (kidney) on
identical twins. Sir then showed a picture of a healthy kidney with the ureter vein and artery resting on the the iliac area. Sabi niya, hindi tinatanggal yung lumang kidneys pag nagtratransplant, dinadagdagan yung kidney, nilalagay ung bago sa iliac area. Thus, 3 na yung kidney nung pasyente :p Tapos picture naman ng kidney na nireject, nagging kulay violet na at ayon sa 2011, 2011, thrombosed na daw. Organs are harvested en bloc from cadaver donors.
What to do to prevent rejection •
•
•
•
•
o
Human T lymphocytes in thymus injected into the horse / rabbit Antibodies against human T lymphocytes are
o
developed Antibodies are injected to the recipient, where T lymphocytes of the recipient will be killed
Organ Donation In some countries, brain dead = organ donor. •
Safety safe safe safe dangerous dangerous dangerous
Here in the Philippines, there are donor c ards. (Back (Back of driver’s license, license, etc)
Brain Death Criteria Deep Coma • •
No breathing
•
No movement (except DTRs) No brainstem reflexes No papillary light reflex o
Gene found in chromosome 6 that is important in
o
transplantation.
o
There are 6 loci, but for organ transplantation, only
o
No blinking No eye movement No grimacing
HLA-A, HLA-B, and HLA-DR matter. (we have 2 of each, therefore, 6 ang minamatch) Blood type must match first before proceeding to HLA matching. The number of matches/mismatches predict the probability of transplant success. Best: 0 mismatch (6 match) o
o
No gagging or coughing
o •
Prevents acute rejection, but not delayed. Patients body eventually recovers and manufactures antibodies.
Drugs – immunosuppressants; anti-thymus globulins o
•
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1960s: whole body irradiation (not done today) o
Human Leukocyte Antigen (HLA) •
Activation and proliferation of antigen specific lymphocyte Damage to donor organ by antibodies.
•
Rules of Tissue Transfer Blood Type Donor Blood Type Recipient Blood Type O* non-O RhRh+ Rh+ RhA non-A B non-B AB** non-AB *Universal Donor; **Universal Recipient
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• •
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Body temp > 32.2 0C A condition that can cause brain death must be established No depressant drugs in blood/ urine
*Bedside diagnosis; transplant surgeon cannot proclaim brain death.
Worst: 6 mismatch (0 match)
However, pwede pa rin magtransplant kahit na 6 mismatch, mas-iiimmunosuppress lang. HLA-DR is most predictive of rejection (kung (kung nagmatch ang isang HLA-DR sa isang donor, kahit
March 17, 2009 | Tuesday
Criteria of Organ Donation Compatibility*
Organ
Age Limit
ABO
HLA
Cornea Kidney Pancreas
65 65-70 15-50
+ +
+ +
Cielo
Co
Maximal tissue Crossmatch ischemia 72 hrs. + 72 hrs. Page + 24 h1 rs.of
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OS 214: Excretory System
Dr. Dennis Serrano
Exam #2
Organ Transplantation, Immunology and Rejection
Liver Lung Heart
65-75 50 55-60
+/+ +
-
+/+/-
18-24 hrs. 6 hrs. 6 hrs.
cascade of immune reactions. Most immunosuppressive drugs used to prevent rejection target the Th.
*+, criterion; -, not a criterion PART 2.
Classification of Rejection 1. Hyperacute
Histocompatibility •
Mutual tolerance between tissues that allows them to be grafted effectively.
Pre-transplant Histocompatibility Testing Blood Typing ABO Blood Group
2.
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Tissue Typing Major Histocompatibility Complex (MHC) Antigens • •
Glycoproteins on cell membranes
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Encoded by MHC genes in short arm of Chr 6
•
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In patients with pre-formed c ytotoxic Ab
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Within minutes to hours after transplant
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In recent years, this has been prevented through
pre-transplant tissue cross-matching Acce ccelerated •
Within days to weeks (~2-3 days)
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Flu-like symptoms
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Humoral and cellular components
Doesn’t respond to anti-rejection treatment Acute With flu-like symptoms as well •
3.
2 Classes: Class I: HLA-A, HLA-B, HLA-C o
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Class II: HLA-DP, HLA-DR, HLA-DQ Tissue Cross-matching
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Myalgia, malaise, fever, decrease in urine output,
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high creatinine, tender graft, HPN Manifests weeks to months post-transplant
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There is graft s welling (local inflammation)
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Tx: increase immunosuppression
o
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Detects circulating PREFORMED cytotoxic antibodies
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Keyword here is PREFORMED o
from previous blood transfusion pregnancy (fetus is considered a foreign body)
o
from from previo previous us transp transplan lantt (these (these patien patients ts are
o
called “sensitized people”; their immune systems have already been alerted before) alerted before)
Indirect
Direct Allorecognition
Recipient
Donor APC
Self-MHC Class II Ag + Allopeptide + Co-stimulatory 2nd
4.
Chronic •
Gradual decline in kidney function
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There is interstitial fibrosis
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Continuous bombardment with focal inflammatory reactions slowly scars kidney tissue
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Manifests years after sugery
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Cannot Cannot be preven prevented ted (Kaya Kaya may lifesp lifespan an ang
AlloMHC Class II Ag + Co-stimulatory 2 nd Th
(IL2, IL 3-6. calcineurin, IF, NFAT) pCTL
B-Cell
+Alloantigen
+ Alloantigen
CTL
Plasma Cell
Cytotoxicity
Alloantibody
Complement Mediated
Macrophage NK Cells Delayed Type Hypersensitivity organ transpl transplants. ants. Pag bata bata ka natranspla natransplant, nt, most probably, you will need a second.) Figure 2. Immunosuppressants and their targets
ADCC
Figure 1. Antigen-Presenting Cells (APC), whether from the recipient or from the donor, are needed to activate Th releas release e of cytoki cytokines nes,, which which would would in turn, turn, activa activate te a
March 17, 2009 | Tuesday
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