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Microbiology and Immunology 2500A/B Lecture Notes - Contraindication, Kidney Transplantation, B Cell

Microbiology and Immunology
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Guest Lecture: Immunology Related to Clinical Transplantation 11/26/2012
Discuss why transplantation is a desirable goal for chronic organ disease and discuss organ shortage
Discuss basic immunology of all responses, including the role of HLA and T cell interactions
Discuss the major current strategies of immunosuppression and their risks
Discuss how patients are matched to potential donors, including ABO blood grouping, HLA matching
Discuss the clinical presentation, lab findings and differential diagnosis of acute graft dysfunction (including
Kidney Function
Regulates salt and water
Produces hormones
Controls blood pressure
Clears waste products
Maintains acid base balance
Kidney failure:
o Functioning at less than 15%
o Kidney failure is usually silent, and is caused by many different factors
Treatments for Kidney Failure
o Hemodialysis
Three times per week
Hospital/satellite unit/home
o Peritoneal Dialysis
Nocturnal cycler
o Deceased donor most common
Neurological death
Cardiac death
o Living donor
Living donor paired exchange
Benefits of Transplantation
Best option for patients with kidney disease who are suitable to receive a transplant
Not a cure disease is still present
Improved quality of life / life saving
o No dialysis
o Decreased cardiovascular risk
o Increased energy
o No diet or fluid restrictions
o More normal lifestyle (freedom)
Kidney Transplantation: It’s a Good Thing
Transplantation offers patients with end-stage renal disease (ESRD) the greatest potential for increased
longevity and enhanced quality of life vs. dialysis
Overall, the 5 year survival rate for patients who received a kidney transplant is 74% vs. 34% for those left on the
waitlist and hemodialysis

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Risks of Kidney Transplantation
Complex surgery
Life-long use of anti-rejection medications to prevent rejection
Side effects of medication
o Infections
o Cancer (skin, lymphoma)
o Diabetes
o Bone disease
Recurrence of original disease
Kidney Transplantation
Own, non-functioning kidney remains
Transplant kidney goes into pelvis
Transplant Outcomes: Donor Organ Dependent
All donors carefully evaluated for kidney function and disease transmission
o Deceased donor: 8 12 years
o Living donor: 12 20 years
1 year graft survival (North America)
o 90% deceased donor kidneys
o 95% living donor kidneys
Challenge: Increasing discrepancy between amount of donors and amount of patients in need of a
Histocompatibility antigens: antigens on tissues and cells that are the target of rejection when grafter between
two genetically different individuals
Major histocompatibility (MHC) antigens: histocompatibility antigens that cause a very strong immune response
and are most important in rejection
MHC complex: group of genes on a single chromosome encoding the MHC antigens
HLA (human leukocyte antigens): MHC antigens of man (first detected on leukocytes)
Human Leukocyte Antigens
T cell responses are not only necessary,
but also sufficient for allograft
T Cell Alloreactivity
T-cell recognition of genetically
encoded polymorphisms between
members of the same species
Principal targets of the immune
response to allogeneic tissues are the
major histocompatibility complex
(MHC) molecules
Recognition of allograft MHC antigen is
the primary event that ultimately leads
to graft rejection
Anatomy of the Allo-Response in Vivo
Donor DC activate the direct pathway of the anti-donor response
Recipient DC presents donor peptides traffic in lymph nodes
Donor DC trafficking to lymph node provide a source of antigen for priming the direct pathway
Recipient DC activate the indirect pathway of the anti-donor response
Loss of donor DC with time
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