OS 214: Excretory System

Dr. Dennis Serrano

Organ Transplantation, Immunology and Rejection

Exam #2

OUTLINE I. Intoduction to Organ Transplantation II. Intoduction to Transplant Immunology and Rejection
PART 1.
Six organs maybe transplanted: • Kidney • Heart • Pancreas • Lung • Liver • Small intestine

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 What Leads to Rejection • Recognition of foreign antigen (donor organ) • Activation and proliferation of antigen specific lymphocyte • Damage to donor organ by antibodies. What to do to prevent rejection

Development of Organ Transplantation

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Replacement of tissue with artificial parts. Dates back several hundred years ago Chinese drawing: heart being taken or replaced Cosmos and Damien (Patron Saints of Transplantation) with angels in the background: replacing a leg o 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 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, thrombosed na daw. Organs are harvested en bloc from cadaver donors. o o

1960s: whole body irradiation (not done today) o Prevents acute rejection, but not delayed. Patients body eventually recovers and manufactures antibodies. Human T lymphocytes in thymus injected into the horse / rabbit Antibodies against human T lymphocytes are developed Antibodies are injected to the recipient, where T lymphocytes of the recipient will be killed

Drugs – immunosuppressants; anti-thymus globulins o

o o

• •

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 Safety safe safe safe dangerous dangerous dangerous

Organ Donation • In some countries, brain dead = organ donor.

Here in the Philippines, there are donor cards. (Back of driver’s license, etc)

Human Leukocyte Antigen (HLA)

• •
• •

Gene found in chromosome 6 that is important in transplantation. There are 6 loci, but for organ transplantation, only 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. o Best: 0 mismatch (6 match) o 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 nagmatch ang isang HLA-DR sa isang donor, kahit

Brain Death Criteria • Deep Coma • No breathing • No movement (except DTRs) • No brainstem reflexes o No papillary light reflex o No blinking o No eye movement o No grimacing o No gagging or coughing


• •

Body temp > 32.20C A condition that can cause brain death must be established No depressant drugs in blood/ urine

*Bedside diagnosis; transplant surgeon cannot proclaim brain death.

Criteria of Organ Donation
Organ Cornea Kidney Pancreas Age Limit 65 65-70 15-50 Compatibility* ABO + + HLA + + Maximal tissue Crossmatch ischemia 72 hrs. + 72 hrs. Page hrs.of + 24 1

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March 17, 2009 | Tuesday

Cielo  Co  Collantes  Concepcion

OS 214: Excretory System

Dr. Dennis Serrano

Organ Transplantation, Immunology and Rejection

Exam #2

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. Histocompatibility Classification of Rejection 1. Hyperacute

Mutual tolerance between tissues that allows them to be grafted effectively.


In patients with pre-formed cytotoxic Ab Within minutes to hours after transplant


2.

Pre-transplant Histocompatibility Testing Blood Typing • ABO Blood Group Tissue Typing • Major Histocompatibility Complex (MHC) Antigens • Glycoproteins on cell membranes • Encoded by MHC genes in short arm of Chr 6 • 2 Classes: o Class I: HLA-A, HLA-B, HLA-C o Class II: HLA-DP, HLA-DR, HLA-DQ Tissue Cross-matching

In recent years, this has been prevented through pre-transplant tissue cross-matching Accelerated

Within days to weeks (~2-3 days)

3.

• Flu-like symptoms • Humoral and cellular components • Doesn’t respond to anti-rejection treatment Acute • With flu-like symptoms as well


Detects circulating PREFORMED cytotoxic antibodies Keyword here is PREFORMED o from previous blood transfusion o pregnancy (fetus is considered a foreign body) o from previous transplant (these patients are called “sensitized people”; their immune systems have already been alerted before) 4.

Myalgia, malaise, fever, decrease in urine output, high creatinine, tender graft, HPN • Manifests weeks to months post-transplant • There is graft swelling (local inflammation) • Tx: increase immunosuppression Chronic


• •

Gradual decline in kidney function There is interstitial fibrosis Continuous bombardment with focal inflammatory reactions slowly scars kidney tissue Manifests years after sugery Cannot be prevented (Kaya may lifespan ang

Indirect Allorecognition Recipient APC Self-MHC Class II Ag + Allopeptide + Co-stimulatory 2nd Signal Th

Direct Allorecognition Donor APC

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AlloMHC Class II Ag + Co-stimulatory 2nd Signal

(IL2, IL 3-6. calcineurin, IF, NFAT) pCTL + Alloantigen CTL Cytotoxicity B-Cell + Alloantigen Plasma Cell Alloantibody Macrophage NK Cells Delayed Type Hypersensitivity
organ transplants. Pag bata ka natransplant, most probably, you will need a second.) Figure 2. Immunosuppressants and their targets

Complement Mediated Damage

ADCC

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 Cielo  Co  Collantes  Concepcion

March 17, 2009 | Tuesday