This presentation will provide an overview about basics of transplantation, types of grafts, process of graft rejection, immunological background about graft rejection, tissue typing procedures, clinical manifestation of graft rejection and graft versus host reaction. The references used for making this presentation is- Kuby Immunology 5th and 7th edition. Other source of information is via internet.
2. OUTLINE
Methods Of Transplants
Autograft & Isograft Acceptance
Immunologic Basis Of Graft Rejection
First-set Rejection
Second-set Rejection
T-cells In Allograph Rejection
Tissue Typing Procedures
1. Blood-group Antigen Test
2. Cross-matching Test
3. HLA/MHC Typing & MLR
HLA In Allograph Acceptance
Tissue-typing Procedures
Cell-mediated Graft Rejection Stages
Clinical Manifestations Of Graft Rejection
Graft-versus-host (GVH) Reaction
References
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) 2
3. METHODS OF TRANSPLANTS
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
What is a graft?
AUTOGRAFT
ISOGRAFT
ALLOGRAFT
XENOGRAFT
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4. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
AUTOGRAFT & ISOGRAFT ACCEPTANCE
Example of :
• Transferring healthy skin to a burned
area
• use of healthy blood vessels to replace
blocked coronary arteries
Example of :
• Performed in genetically identical
(monozygotic) twins
• Inbred strains of mice; one mouse
to another syngeneic mouse
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5. IMMUNOLOGIC BASIS OF GRAFT REJECTION
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
FIRST-SET REJECTION
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6. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
IMMUNOLOGIC BASIS OF GRAFT REJECTION
SECOND-SET REJECTION
CD4+
CD8+
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7. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
T-CELLS IN ALLOGRAPH REJECTION
Avrion Mitchison experiment (1950s)-T Cells Play a Key Role in Allograft
Rejection
Deletion of Graft survival
CD8+ T-cell 15 days
CD4+ T-cell 15-30 days
CD4+ & CD8+ up to 60 days
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8. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
TISSUE TYPING PROCEDURES
1. Blood-Group Antigen Test
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9. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
TISSUE TYPING PROCEDURES
2. Cross-Matching Test
The Luminex cross-matching assay
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10. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
HLA IN ALLOGRAPH ACCEPTANCE
• Histo-compatible and Histo-
incompatible
• Ag(MHC) are responsible for
graft rejection
• Organization– mice(H2
complex); Human(HLA)
• Haplotype – Inheritance of
complete set
• Inbred mice(Homozygous) and
outbred mice (25%)
• e. g Organ and Bone marrow –
identity between sibling 25%
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11. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
Mixed lymphocyte reactionHLA typing
Microcytotoxicity test
(a)
TISSUE TYPING PROCEDURES
3. HLA/MHC TYPING & MLR
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12. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
CELL-MEDIATED GRAFT REJECTION STAGES
1. Sensitization Stage
• CD4+ and CD8+ T cells recognize
alloantigens & proliferate
• Donor APCS called passenger
leukocytes to migrate from graft to the
regional lymph nodes
2. Effector Stage
• Cell-mediated reactions: delayed-type
hypersensitivity & CTL mediated
cytotoxicity
• Influx of T cells and macrophages into
the graft
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13. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
CLINICAL MANIFESTATIONS OF GRAFT
REJECTION
1. Hyperacute rejection: ( within minutes )
• Mediated by humoral immunity
• Recipient already have antibodies against the graft
• Pre-existing antibodies will attach to the organ & activate
complement system to destroys organ within minutes
2. Acute rejection: ( about 10 days )
• The graft persist for about 10 days
• T cells-cell mediated, take longer time to multiply and
arrive
3. Chronic rejection: ( months-years )
• Atherosclerosis Of The Vascular Endothelium
• By Both Cellular And Humoral Immune Components
• Side Effects Of Immunosuppressive Drugs
Hyperacute rejection of a kidney graft
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14. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
GRAFT-VERSUS-HOST (GVH) REACTION
• Transplanted bone marrow or
thymus which are have a large
number of lymphocytes from
the donor
• Donor’s cytotoxic T cell will
play a major role in destroying
the recipient’s cells
• Symptoms: maculopapular rash,
jaundice, hepatosplenomegaly
and diarrhoea
• GVH reactions usually end in
infections and death
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15. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
REFRENCES
Kuby Immunology 5th and 7th edition
HLA Complex image
https://www.quora.com/How-do-our-immune-cells-recognize-self-
and-nonself
Blood Group Test image
https://thecentraltrend.com/16020/showcase/american-red-cross-
introduces-blood-typing-to-human-anatomy-and-physiology-
students/
Graft-Versus-Host Disease
http://chemosabe-socks.blogspot.in/2013/07/graft-versus-host-
disease.html
All Other Images: Kuby Immunology 5th snd 7th edition
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