Transplantation
Abdul Waheed
IFBA Certified professional
Master trainer PBSA
Master trainer UHS
Government College University Faridabad
[email protected]
0333-7437667
Transplantation
Transplantation
Transfer of living cells, tissues and organs from one part of the
body to another or from one individual to another.
Transplantation
◼ Implantation of “non-self” tissue into the body
◼ The process of taking cells, tissues, or organs called a
graft (transplant), from one part or individual and
placing them into another (usually different individual).
◼ Donor : the individual who provides the graft.
◼ Recipient or host: the individual who receives the graft.
Allograft: Transplant
• Transplant from one individual to another with a different
genetic make-up, within the same species, eg. kidney
transplant from one person to any other
Isograft or syngeneic graft
Transplant between genetically identical
Isograft
Auto graft
➢ Transplant from one site to another on the same individual, eg.
transplanting a blood vessel from the leg to the heart during cardiac
bypass surgery. This type of transplant does not require
immunosuppressive therapy
Xenograft
Transplant across species barriers
Dark-colored urine
Itchy skin
Fluid buildup in your abdomen (ascites)
Swelling in your legs
Weight loss
Confusion, drowsiness and slurred speech
Spiderlike blood vessels
Transplant antigens
MHC
Gene complex whose alleles encode polymorphic cell surface
glycoproteins involved in antigen recognition and presentation
HLA
Classes of MHC
Factors favoring Allograft Survival
➢ Blood group compatibility
➢ HLA compatibility
➢ HLA typing and Tissue matching
➢ HLA typing identifies the HLA antigens expressed on the
surface of leukocytes.
Identifying MHC polymorphisms
➢ Formerly determined by antibodies against MHC molecules
➢ HLA typing
➢ MLR
➢ Now by DNA testing: allele-specific PCR, sequencing
Tissue typing
• Microcytotoxicity assay
– Known antibody to WBCs of donor / recipient
– Complement mediated lysis if Ab present on cell surface
• Mixed lymphocyte culture (MLC)
– Irradiated donor lymphocytes (stimulants)
– Incubated with recipient lymphocytes
• Flow cytometry cross typing
• DNA analysis
Genomic typing
Clinical phases of rejection
1. Hyperacute rejection (minutes to hours)
• Preexisting antibodies to donor HLA antigens
• Complement activation, macrophages
2. Acute rejection (around 10 days to 30 days)
• Cellular mechanism (CD4, CD8, NK, Macrophages)
3. Chronic rejection (months to years !!)
• Mixed humoral and cellular mechanism
• CHRONIC REJECTION IS STILL HARD TO MANAGE !
Hyper acute Rejection
▪ Occurs within a few minutes to a few hours
▪ Result of destruction of the transplant by performed antibodies
(cytoxic antibodies)
▪ Some produced by recipient before transplant
▪ Generated because of previous transplants, blood transfusions,
and
▪ pregnancies
▪ Antibodies activate the complement system then platelet
activation and deposition causing hemorrhaging and swelling
Chronic rejection
▪ Caused by both antibody and cell-mediated immunity
▪ May occur months to years down the road in allograft
▪ transplants after normal function has been assumed
▪ Important to point out rate, extent, and underlying mechanisms of rejection
that vary depending on tissue and site
▪ The recipients circulation, lymphatic drainage, expression of MHC antigens and
other factors determine the rejection rate
▪ Inflammation, smooth muscle proliferation, fibrosis
▪ Tissue ischemia
Graft-vs-host disease
• Graft-vs-host disease can occur in the special case in which
immunocompetent tissue is transplanted into an
immunocompromised host.
• T cells from the transplant recognize the host MHC molecules as
nonself and attack the host
Privileged Sites?
Graft acceptance
If the recipient posses all the antigens present in the graft
there will be no immune response, and no graft rejection
Control of Transplant Immunology
➢ Transplantation immunity is predominately by cell mediated
Immunity First response is mediated by T lymphocytes
➢ Humoral antibody are also produced during Allograft Rejection
What happens after Two to Three days
⚫ The site around transplantation is inflamed, invaded by
lymphocytes, Macrophages
⚫ Blood vessels occluded by thrombi
⚫ Vascularity to graft diminishes
⚫ Ischemic changes sets in
⚫ Scab like changes appear, sloughs out 10th day
⚫ Above response is called Ist set response
Prolonging Allograft Survival
• Anti-inflammatory Agents
• Cytotoxic Drugs
• Agents that interfere with Cytokine production and signaling
• Immunosuppressive Therapies
• New Immunosuppressive strategies
Laboratory Tests
• ABO Blood typing
• Tissue typing (HLA Matching)
• (Lympho cytotoxicity test)
• (Mixed leukocyte reaction)
• Screening for Presence of Preformed Antibodies to allogeneic HLA
• Crossmatching
