2-4-10 Transplant Immunology 1. Be able to define the four types of organ transplant rejection.

Look at three cases at the end of this lecture. Hyperacute rejection: caused by ABO mismatch during solid organ transplants, so pre- ormed antibodies attac! oreign transplanted tissue, triggering complement" Occurs #ithin irst 24 hours a ter transplant$ %istopathology: thrombosis &'I: you can ha(e ABO mismatched bone marro#, as long as you ablate all the red cells prior to transplantation Acute vascular rejection: caused by recognition o endothelial antigens" 1) T cells are acti(ated to attac! the gra t (essel and 2) alloantibodies attac! oreign transplanted tissue, triggering complement" Occurs a ter a couple o #ee!s rom transplantation" %istopathology: vasculitis Acute cellular rejection: *aused by helper T+s recruiting cytoto,ic T cells to attac! the parenchyma o the solid organs" -T% .delayed-type hypersensiti(ity) also plays a role in acute cellular re/ection" 0ill notice based on en1yme assays2cyto!ine release .I3-2, I&4-gamma, %3A--5)" Occurs o(er time .ta!es a#hile)" %istopathology: patchy parenchymal necrosis #ith lymphoid in iltration .only the parenchyma is attac!ed, rest o organ is O6) Chronic rejection: *aused by cyto!ine release rom T cells in response to alloantigens" Occurs a ter many years .this #e hear about this a lot)" %istopathology: ibrosis 2. Define strategies to prevent rejection.
1" 2" 7" 4" 9" :"

closely match donor and recipient remo(e pre- ormed antibodies rom recipient to pre(ent hyperacute re/ection bloc! co-stimulatory molecules .i"e" *-28) reduce the immunogenicity o the gra t immunosuppressi(e meds engineer a gra t to !ill in iltrating lymphocytes

. Define the co!plications of i!!unosuppressive !edications. The main problem is in ection;(iral .especially *<=) and ungal" The other is malignancies;>B= lymphoproli erati(e disease, !aposi+s sarcoma, s?uamous cell carcinoma ". Define the causes of graft vs host disease and strategies to prevent this co!plication.

There+s a so-called @yin-yangA to %B*T" 'ou get t#o results: the recipient+s T cells reject the donor cells" In this case, you didn+t suppress the patient+s immune system, and the patient !ills the gra t" or the donor+s T cells @re/ectA the recipient+s cells: graft versus host disease .C(%-)" In this case, you don+t suppress the immune system o the gra t #ell enough, and the gra t #ill attac! the host" C(%- is caused #hen donor T cells .trans erred into the recipient #ith the %B*T) react against antigens on the cells o the recipient" These allo-reacti(eA donor T+s in iltrate tissues and cause in lammation, especially in s!in, gut, and li(er" Thus, C(%- is seen in these cases: Transplantation, especially o bone marrow and small bowel Blood trans usion, especially o congenital immunodeficiency, cancer patients receiving immunosuppressive drugs, and immunosuppressed surgery patients" <ust gi(e irradiated blood products to a neonate or an immunosuppressed patient$ Transplancental passage o maternal T cells into im ants #ith B*I B*I- babies #ill get a rash #ith trans usions that aren+t irradiated %B*T is most commonly done or the treatment o resistant leu!emia or cancer" %igh dose chemo ablates the patient+s normal %B*, so %B*T is gi(en to replenish %B* unction" C(%- symptoms include: s!in rash .acute erythema2chronic sclerotic and pleomorphic), CI .acute diarrheaD chronic malabsorption and dysmotility), and li(er .acute hepatitis, chronic biliary sclerosis) Ere(ention o C(%-: A ter B<T: Ehysical remo(al o T lymphocytes rom donor gra t Immunosuppressi(e meds Tolerance induction Ablation o recipient dendritic cells &rom trans usions: Irradiation o blood products to !ill immunocompeetent T cells