College aantekeningen
Notes lectures Nephrology theme Minor Clinical Immunology
- Instelling
- Universiteit Leiden (UL)
Complete notes of all lectures given during the Nephrology theme during the Minor Clinical Immunology at the LUMC.
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LT IntroductionExamples of glomerulonephritis:
- IgA nephropathy is characterized by inflammation of the kidney including activation
of the complement
- SLE is a systemic disease but also includes lupus nephritis
- ANCA vasculitis is an autoimmune disease characterized by antibodies directed
against neutrophils
- iMN (= membranous nephropathy) is caused by anti-PLA2R antibodies directed
against podocytes
- aHUS
When antibodies are involved, the complement system is often activated; therefore,
there’re also cytokines involved because of the inflammation; often T cells are also involved
I/R injury (= ischemia/reperfusion injury) is mediated by the complement and innate
immunity
Hyper acute rejection is mediated by preformed antibodies
Acute rejection is mediated by cellular immunity
Chronic rejection is mediated by humoral immunity
These reactions occur after one another; when these reactions don’t occur, there’s tolerance
of the transplant
Allogeneic T cells directly recognize foreign HLA molecules
First, positive selection of T cells occurs during which T cells that are able to recognize their
own MHC molecules with intermediated affinity (not too low or high) are selected; after,
negative selection occurs (both within the thymus)
Direct allorecognition = crossreactive with foreign MHC; indirect allorecognition can occur in
a later stage after transplantation, it that situation, parts of donor MHC are presented by the
recipient dendritic cells
Co-stimulation is mediated by B7 on APCs and CD28 on T cells
Specialization in CD4 T helper cell responses is dependent on cytokine production
LT Systemic lupus erythematosus
IgA, IgG, C1q and C3c are present in the glomeruli of the kidneys in SLE patients
The antibodies involved are anti-nuclear autoantibodies (ANAs); these antibodies are
developed after nuclear molecules are released into the circulation after necrosis
(unregulated type of cell death) or NETosis
In SLE patients, there’re immune complexes present which trigger the neutrophils to be
activated and do NETosis (causing production of ANAs)
In SLE patients, there’s B-cell hyperactivity due to the continuous exposure to DNA
Symptoms: complaints of joints, malaise, less appetite, anorexia, malar skin rash (butterfly,
stimulated by sun exposure), renal disorder it’s a systemic disease; very heterogenous
disease
Diagnostic criteria both include clinical and immunological characteristics
, Treatment used in the past years were prednisone, cyclophosphamide, azathioprine or
cellcept; the ultimate combination is still under investigation
LT Hemolytic uremic syndrome (HUS)
HUS is a thrombotic microangiopathy (TMA) which is a disease of the small vessels caused by
development of thrombi
The kidneys are susceptible for TMA since they have a different endothelium (fenestrated
with podocytes and glycoproteins)
Most effected by hypertension are the eyes, brain, kidneys
TMA is often characterized by hemolysis (leads to low Hb, thrombocytes, haptoglobin and
high LDH and bilirubin)
Within the kidneys, there’s protection against fluctuations in blood pressure by
autoregulation, so the blood pressure is constant within the kidneys
Chronic/malignant hypertension leads to remodeling of blood vessels (increased connective
tissue); it also activates immune and thrombotic responses
The thrombotic activation results in production of fibrine which damages the red blood cells
TTP (type of TMA) is caused by a decreased ADAMTS13 activity; ADAMTS13 cleaves the van
Willebrand factor; when not active, thrombi formation occurs; TTP is characterized by acute
neurology, renal insufficiency, hemolysis and cardiac thrombi
Treatment used is plasma exchange to remove autoantibodies or inhibition of the antibodies
by B cells (rituximab)
MOOC Clinical kidney transplantation
Serological HLA typing is done by adding the lymphocytes of the person who is typed to
different sera
When the serum contains antibodies, which recognize the HLA antigens on the lymphocytes,
they will bind and activate complement leading to hemolysis (resulting in red dye)
Molecular typing (by using the genome) is more detailed, and the analysis is standardized
MOOC Early challenges
Early challenges in kidney transplantation are:
- Failure of renal function caused by surgical complications (thrombosis, bleeding,
wound complications, lymphoceles)
- Delayed graft function caused by decreased donor source, increased donor age,
prolonged ischemia time, bad storage conditions or renal dysfunction of donor
- Acute rejection caused by HLA mismatching, sensitization, ABO incompatibility,
infection, adolescent
- Recurrent disease
- Prerenal causes such as hypertension
- Calcineurin toxicity
- Infections
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