module 6 Flashcards
what is HLA AND MHC
HLA is human leukocyte antigen- inherited as a haplotype letter is locus and number is the antigen eg A2
MHC- major histocompatibility complex
-genes for HLA Ag are located on MHC gene system on chromosome 6
the MHC genes are divided into 3 classes
Class 1 - A, B, C loci (organ transplants)
Class 2 - DR, DP, DQ loci
Class 3 - codes for complement proteins and cytokines
where are HLA class 1 and HLA class 2 Ag found
HLA Class1 Ag- found on surface of platelets, leuko, and most nucleated cells, retics
HLA Class 2 Ag - on Ag presenting cells - macrophages, dendritic cells and B cells
there are more Class 1 then class 2
-because class 2 are not found on platelets its not needed to match class 2 Ag when HLA compatible platelets are requested
-HLA matching most important for tissue or organ transplant
how to test and idenifty HLA/MHC
- serologic identification needs a lymphocytotoxicity test method using dye and complement to see if there is a AG-AB reaction
-positive reaction will have cells taking up the dye and staining dark
serologic methods are being replaced by molecular methods because AB can be cross reactive or react to more than one epitope
-AB for many different for HLA Ag have not been developed yet
what do you need for a succesful transplant
ABO compatibility
-Matching HLA Ag in patients with existing Ab
Patients can become sensitized (develop HLA Ab) to HLAs by:
Pregnancy
Blood transfusions (CBS gives leuk reduced blood to decrease chances for sensitivity)
Previous transplant
how do you test for HLA Ab before organ transplant
Panel reactive antibody
-CPRA
cross matching
1- Serological test on microtiter with panel of common HLA Ag
2-Panel reactive antibody - PRA looking for number of HLA AB detected
-high PRA - many reactions - HLA reactions - not very compatible
3-CPRA - newer method based on antigens that organ candidate is reactive against - unacceptable antigens
-helps to rank recipient on organ waitlist
- Cross matching- recipient serum with T & B cells (that is where cd surface markers are) from donor to avoid rejection caused by AB to donor tissues - IMMUNO-FLUORESCENT FLOW CYTO
Hematopoietic Progenitor Cell (HPC) Transplants
-HPCs can be obtained from bone marrow, peripheral blood, and cord blood
-used to treat diseases: e.g. aplastic anemia, leukemia, lymphoma, and Hodgkin’s disease
-HLA matching at the allelic level is important to avoid rejection and graft-versus-host disease (GVHD)
-Preformed HLA antibodies and ABO compatibility less important in HPC transplants compared with solid-organ transplants
Platelet Antigens
-platelets display HLA class I antigens: A, B, and C
-platelet antibodies less frequent because there is less platelet antigen variability in population
Platelet Antibodies
Neonatal alloimmune thrombocytopenia (NAIT):
Post transfusion purpura (PTP)
Antibodies to platelets may cause:
- Neonatal alloimmune thrombocytopenia (NAIT):
destruction of newborn platelets by maternal antibody (when mom creates AB against the Ag that is inherited from the father in the fetus’ platelets)
-therapy transfuse them with washed maternal platelets or antigen-negative donor platelets - Post transfusion purpura (PTP)
destruction of platelets by platelet antibodies after transfusion
Platelet recipients can become refractory - unresponsive:
-unresponsive to platelet transfusion
-can receive HLA-matched platelets or serum crossmatched to detect platelet antigen incompatibility before transfusion
most common platelet AB is HBA1A
what is graft vs host disease
-Donor lymphocytes (graft) multiply and attack the patient cells (host)
-Recipient are often on immunosuppressants
-Donor cells able to multiply
-Organ rejection is more likely to occur
-Allele-level matching important for optimal graft survival
-irradiating prevents viable or live donor leuk from replicating and destroying mitotic activity and blast formation
-different from leuk reduction because small amounts can still live and proliferate
- in bone marrow transplants you dont irradiate the HSC because you need them to proliferate
what does the lab see when you have GVHD
-decreased totel lymph concentration signaling immunosuppression or deficiency
-as GVHD progresses- how is inflammation evident
- increased CRP
-increased leuko with granulocytosis
-increased ESR
-anemia and liver disease
-presence of opportunistic pathogens - cyto megalovirus
pathologically you see :
-lymph and mono move into perivascular spaces of dermis, oropharynx, tongue and esophagus
-move into crypts of bowls, liver with 2ndary necrosis
