03/15f Immunopathology II Flashcards
What tissues can you transplant?
Vascularized solid organs - kidney, liver, heart, lung, pancreas, small bowel
Cornea
Skin
Bone marrow
Blood and blood products
Cell suspensions - pancreatic islet cells, fetal adrenal cells
What is an isograft?
Transplant between genetically identical donor and recipient
What is a xenograft?
Transplant between donor and recipient of different species
Can be concordant (preformed antibodies are absent) or discordant (preformed antibodies are present)
What is an orthotopic graft?
A graft implant at the same site as the organ it replaces - done for heart, lung, liver, and small bowel
What is a heterotopic graft?
A graft implanted at a site distinct from the organ it replaces - done for kidney, pancreas
What are the three categories of allograft donors?
Living related
Living unrelated
Cadaveric/deceased donors
What are the four modes of allograft rejection?
Hyperacute
Accelerated
Acute
Chronic
What is the timecourse and mechanism of hyperacute rejection
Timecourse - minutes to hours
Mechanism - binding of preformed antibodies to graft antigens (usually HLA or ABO), followed by complement fixation, attraction of neutrophils, and tissue damage
What is the histology of hyperacute rejection? How is it treated?
Site of attack - vascular endothelium, especially in kidney and heart transplant patients
Histology - hemorrhage, edema, vascular necrosis, acute inflammation
No satisfactory therapy
Why would a recipient have prior sensitization to an allograft?
Blood transfusion
Pregnancy
Previous allografts
Natural immunity - ABO blood groups
How is hyperacute rejection avoided?
Through cross-matching - testing of recipient serum for antibodies that are reactive with donor lymphocytes
Cross-match is done through flow cytometry or testing complement-mediated cytotoxicity
What is the timecourse and mechanism of accelerated graft rejection?
Onset - days to weeks after graft (starts within days)
Mechanism - may involve antibodies produced after graft, or small quantities of preformed antibodies
What is the histology of accelerated rejection? How is it treated?
Site of attack - vascular endothelium
Histology - hemorrhage, edema, vascular necrosis, acute inflammation
Therapy - plasmaphoresis, IVIG, Rituximab (anti-CD20)
What is the timecourse and mechanisms of acute graft rejection?
Onset - weeks to months after graft (starts within days)
Mechanism - recognition of graft antigens by allospecific T cells, followed by cytotoxicity (CD8 T cells) and release of inflammatory cytokines (CD4 T cells)
What are the sites of attack of acute rejection, according to organ?
Kidneys - tubules, interstitium
Liver - venous endothelium, bile ducts
Heart - myocytes
Lung - arterioles
What is the histology and treatment of acute rejection?
Histology - infiltration of lymphocytes and macrophages, tissue damage, hemorrhage and necrosis in severe cases
Treatment - pulse IV steroids, anti-T cell antibodies
How is acute rejection prevented?
Donor-recipient matching through HLA typing
Pre-transplant conditioning - immunosuppressive agents
Post-transplant therapy - immunosuppression, prednisone
What is the timecourse and mechanism of chronic allograft rejection?
Onset - months to years after graft
Mechanism - unknown, but probably a mixture of cell-mediated and antibody-mediated rejection
What are the sites of attack of chronic rejection, according to organ?
Kidney - vasculature, tubules, interstitium
Liver - bile ducts (“vanishing bile ducts”), chronic arteriopathy
Heart - vasculature
Lungs - bronchioles (bronchiolitis obliterans)
What is the histology and treatment of chronic rejection?
Histology - fibrosis, atrophy, vascular thickening
No satisfactory treatment available, besides re-transplant
What are some other problems involved in solid organ grafts, besides rejection? List six
Recurrence of the original disease
Occurrence of a new primary disease
Infection of the graft, or multi-systemic infection
Immunosuppressant drug toxicity
Failure of anastomoses
Malignancies due to immunosuppression - lymphoproliferative disorders, skin cancers
Why do we do bone marrow transplants?
To treat heritable or acquired hematopoietic disorders, such as SCIDS or aplastic anemia
To perform marrow reconstitution follow cancer therapy for leukemias and some solid tumors
What are some complications of bone marrow transplantation?
Failure to engraft
Graft-versus-host disease
Infection
Recurrence of primary tumor
