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Samruddhi Arun Shinde
M.Sc. I Biotechnology
PSBT 102: Immunology
Unit II: Molecular Immunology
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
METHODS OF TRANSPLANTS
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
What is a graft?
 AUTOGRAFT
 ISOGRAFT
 ALLOGRAFT
 XENOGRAFT
3
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
4
IMMUNOLOGIC BASIS OF GRAFT REJECTION
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
FIRST-SET REJECTION
5
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
IMMUNOLOGIC BASIS OF GRAFT REJECTION
SECOND-SET REJECTION
CD4+
CD8+
6
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
7
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
TISSUE TYPING PROCEDURES
1. Blood-Group Antigen Test
8
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2)
TISSUE TYPING PROCEDURES
2. Cross-Matching Test
The Luminex cross-matching assay
9
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%
10
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
11
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
12
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
13
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
14
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
15
Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) 16

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Transplantation Immunology -by Samruddhi Shinde

  • 1. Samruddhi Arun Shinde M.Sc. I Biotechnology PSBT 102: Immunology Unit II: Molecular Immunology
  • 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 3
  • 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 4
  • 5. IMMUNOLOGIC BASIS OF GRAFT REJECTION Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) FIRST-SET REJECTION 5
  • 6. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) IMMUNOLOGIC BASIS OF GRAFT REJECTION SECOND-SET REJECTION CD4+ CD8+ 6
  • 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 7
  • 8. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) TISSUE TYPING PROCEDURES 1. Blood-Group Antigen Test 8
  • 9. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) TISSUE TYPING PROCEDURES 2. Cross-Matching Test The Luminex cross-matching assay 9
  • 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% 10
  • 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 11
  • 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 12
  • 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 13
  • 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 14
  • 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 15
  • 16. Samruddhi A. Shinde, M.Sc. I (Biotechnology), PSBT 102 (Unit 2) 16