8. Immunological Aspects of the Renal System Flashcards
What is the presentation and type of hypersensitivity for graft-versus-host disease?
Patients present with diarrhea, rash, and jaundice.
This is a type IV hypersensitivity.
What is the role of Th-17 cells in acute renal injury?
Secretes interleukin 17 to begin the pro-inflammatory process, and primarily leads the recruitment of neutrophils.
May also recruit monocytes, Th1, and Th-17 cells, via Macrophage Inflammatory Protein-3 (CCL20)
What are the two effector mechanisms of graft rejection, and what cells mediate them?
Humoral rejection – Th2
Cellular rejection – Th1
What is an autograft, isograft, allograft, and xenograft?
Autograft: between the same individual.
Isograft: between two individuals of identical genetic constructions (identical twins)
Allograft: graft exchange between nonidentical members of the same species
Xenograft: graft exchange between members of different species
What are the time frames for hyperacute, acute, and chronic rejections?
Hyperacute: immediate
Acute: days/weeks/months
Chronic: months to years
How does the complement system result in death of renal cells in acute kidney injury? (Three mechanisms.)
Directly, via MAC complex overexpression.
By releasing C3a and C5a, which activate neutrophils, which releases a respiratory burst.
Alternatively, the same neutrophils can release pro-inflammatory cytokines that cause necrosis of renal cells.
Why might ABO antigens be a barrier to transplantation in someone with O- blood?
Because A/B antigens can be present on the organs of individuals without A/B antigens on their red blood cells.
What are the five immune events in allograft rejection?
Antigen presenting cells trigger CD4+ and CD8+ T cells
Both a local and systemic immune response develops
Cytokines recruit and activate immune cells
Development of T cell, NK cell, and Macrophage mediated cytotoxicity
Allograft rejection
What is the difference between direct and indirect allorecognition?
During direct allorecognition, T cells recognize intact allogeneic molecules on the surface of donor antigen presenting cells in the graft.
During indirect allorecognition, the alloantigens are recognized in the context of the recipient’s own antigen presenting cells – after processing and loading onto MHC class II.
What are the two effector mechanisms of graft-versus-host disease?
Fas-FasL
Perforin/Granzyme
Between HLA class-I and class-II, which is the main barrier to transplantation?
HLA class I, because it is present on every cell.
What two cytokines induce differentiation into Th17?
IL-6 and TGF-beta
What is the mechanism of cytotoxicity in acute graft rejection?
The DONOR’s dendritic cells migrate to the host’s lymph nodes, stimulating a response. Once activated, the host’s T cells migrate to the organ – where they generate cytotoxic T cells and induce type IV hypersensitivity reactions.
OR
An indirect response to the donor’s MHC (processing and presentation by host’s MHC II)
How is the mixed lymphocyte response test performed, and what does it test for?
In the Mixed Lymphocyte Response (MLR) test, donor cells are irradiated so as not to proliferate, and then are exposed to CD4+ recipient cells. H3-thymidine is added to the broth and is uptaken by the recipient’s cells. If the recipient’s cells respond to the class II MHC of the donor, they will proliferate. Excess H3-thymidine is then washed out of solution, and the H3-thymidine in the cells is counted. If the recipient’s cells responded to the class II HLA of the donor, we will see a large amounts of H3-thymidine remaining.
What are the five DAMPs discussed in this lecture?
HMGB1
Uric acid
HSPs (Heat Shock Proteins)
S100 protein
Hyaluronans in the ECM
How does the complement system cause fibrotic repair in acute kidney injury?
C3a and C5a summon neutrophils, which release pro-inflammatory cytokines, which summon M2 macrophages,
What are the four variables that determine transplant outcome?
The condition of the allograft
Donor-host antigenic disparity
Strength of host anti-donor response
Immunosuppressive regimen
What sort of graft can cause graft-versus-host disease?
A graft with a significant amount of donor T cells – such as:
Bone marrow
Small bowel
Lung
Liver
What is the criteria for chronic kidney disease?
A GFR of less than 60 mL/min per 1.73 m² for more than three months.
OR
Signs of kidney damage for greater than three months.
How is the micro-cytotoxicity test for preformed antibodies performed?
Add the donor’s cells to the recipient’s serum.
Add complement and a special dye.
Examine the donor’s cells under a microscope, to see if the dye entered the cells via the MAC-attack complex.
What can be caused by ischemic acute kidney injury?
Metabolic acidosis and ATP depletion – leading to acute renal failure
How might acute kidney injury trigger autoimmunity?
Which type of hypersensitivity would this be?
When the kidneys are injured, positively charged antibodies can interact with the glomerular basement membrane. This results in anti-glomerular basement membrane antibody-mediated glomerulonephritis.
This is a type II hypersensitivity.
What two things will occur immediately following kidney implantation if the organ is damaged prior to the surgery?
The clotting cascade will cause the creation of fibrinopeptides, which will increase vascular permeability, attract neutrophils, and attract macrophages.
The kinin cascade will produce bradykinin, which will increase vascular permeability, cause vasodilation, and smooth muscle contraction.
(Both of these responses together will result in hyper-acute allograft rejection)
In renal tissue injury, which T cells predominate in the earlier stages, and which predominate in the later stages?
Th-17 cells predominate in the early stages of renal tissue injury.
Th-1 cells predominate in the later stages of renal tissue injury.
