Immune Aspects of the Renal System Flashcards
(49 cards)
What is an acute rejection caused by?
Primary activation of T cells (Th1 cells and CTLs) –> parenchymal cell damage, interstitial inflammation
donor DCs migrate to lNs –> generate response
weeks to months
What compliment pathways have been linked with kidney diseases?
all of them!
What cascade occurs when graft tissues are damaged?
clotting cascade –> fibrin and fibrinopeptides –> fibrinopeptides = vascular permeability and attract neutrophils and macrophages –> bradykinin –> vasodilation, sm m contraction, etc
if uncontrolled –> hyperacute rejection
What T cells predominate in earlier stages of renal tissue injury?
What about late stages?
Th17 = early
Th1 = late
What are convenient sources of lymphocytes for HLA typing?
spleen and LN (from cadavers)
peripheral blood
How can some transplant recipients have pre-existing Abs to a graft?
ABO blood group incompatibility
recipient has been sensitized to donor MHC by previous transplants, multiple blood infusions, or pregnancy
How do you do specific microcytotoxicity test for class I HLA?
Have separate containers w/ donor cells and recipient cells
add Abs –> add complement –> add dye –> If both donor and recipient cells accumulate dye = have identical HLA Ags
If only one type of cell accumulates dye –> Ags are different!
What are the immune events in allograft rejection?
- APCs trigger CD4 and CD8 T cells
- botha local and systemic immune response develop
- cytokines recruit and activate immune cells
- development of specific T cells, NK cells, or macrophage-mediated cytotoxicity
- Allograft rejection
What do Tregs do in AKI?
release TGF-beta and IL-10 –> anti-inflammatory
What is C-reactive protein?
5 subunit protein (like IgM) –> can activate classical path of compliment
What is type III hypersensitivity and when do you see it in kidney disease?
IgG or IgM binds a soluble antigen –> Ag-Ab complexes deposite in tissues –> complement –> neutrophils release enzymes that damage tissue
post-streptococcal GN, rheumatoid arthritis, lupus
What 4 factors determine transplant outcomes?
- condition of allograft
- donor-host antigenic disparity
- strength of host anti-donor response
- Immunosuppressive regimen
What type of T cell is involved in humoral rejection?
cellular rejection?
humoral = Th2
cellular = Th1
What is a xenograft?
graft exchanged btw members of different species
particularly susceptible to rapid attack
insertion of human genes into genomes of donor animals increases chances of successful survival
What is the typical source for HLA antisera for specific ags?
multiparous women or from planned immunization of volunteers
What is type II hypersensitivity?
mediated by IgM or IgG
cell-bound antigen –> Ig binds –> complement activation
see in anti-glomerular basement membrane antibody-mediated GN
What is graft-versus-host disease caused by?
reaction of grafted mature T cells with allo-Ags of the host
against minor H Ags
usually for bone marrow transplants, also small bowel, lung, or liver (also contain some T cells)
What is indirect allorecognition?
professional APC takes and processes allogeneic MHC molecule –> presents to T cell –> response
How is microcytotoxicity for preformed Abs performed?
recipient serum is added to donor cells –> complement added –> dye added
if dye accumulates in cells = preformed Abs for donor cells are present in recipient
This is for HLA I/II Abs
What are the 2 effector mechanisms of GVHD?
Fas-FasL
perforin/granzyme
What do you see in acute GVHD?
What about chronic?
acute = epithelial cell death in the skin, liver, and GI
chronic: fibrosis and atrophy of affected organ
What is the function of M2 macrophages in kidney disease?
tissue repair and fibrosis
What is an allograft?
grafts exchanged between nonidentical members of the same species (most transplants)
Where are HLA genes located?
chromosome
Class I = ABC
Class II = DP, DQ, DR
