Renal Immunology Flashcards
(40 cards)
What is one of the major causes of Acute renal failure ARF
Ischemic acute kidney injury leading to metabolic acidosis and ATP depletion
What induces sterile renal inflammation
DAMPs released from dying parenchymal cells or during ECM degradation and remodeling
Activate PRRs causing release of TNFa, IL-6, IL-1
What activates complement pathways and what type of receptors are activated to induce innate immune response in sterile renal inflammation
CRP binds damps activating complement classic pathway Immune cells (dendritic, macrophage, endothelial cells) recognize DAMPs via TLRs inducing innate immune response
Macrophage activation
IFN-y is major cytokine activating macrophages
Macrophages are single largest contributor to inflammatory cytokines in body
M1 vs M2 macrophage
M1 play key role in acute kidney injury
-induced by PAMPs and DAMPs binding TLR/PRR
-IFN-y promotes their differentiation
-release IL-1/12/23, ROS/NO
M2 play key role in tissue repair
-activated by IL-4/13
-release IL-10 and TGF-b promoting repair
Early stage vs late stage of AKI what T cells dominate
Early stage is Th17 cells
Late stage is Th1 cells
Macrophage reprogramming
M1 macrophages can be reprogrammed to M2 macrophages by CSF-1 and IL-10
Macrophage stimulation of matrix deposition/tissue repair
Profibrotic factors TGF-b and PDGF attracting pericyte accumulation which differentiate into myofibroblasts and produce ECM
Th17 function
Secrete IL-17 stimulating resident renal cells to produce inflammatory mediators
IL-17 induces expression of CCL20 (MIP3-macrophage inflammatory protein 3) leading to neutrophil (mainly), monocyte, Th1 and Th17 cell recruitment
What causes the kidneys unique susceptibility to complement induced damage
Filtration favors tissue deposition of immune complexes
Compliment pathway role in damage
AKI and tissue damage leads to excessive generation of DAMPs which activate resident immune cells via PRRs
C3b and C5a activation causes further activation of tissue resident cells
Deposition of membrane attack complex leads to massive cell death
Which types of hypersensitivity reactions usually occur in AKIs
Type II and Type III
Type II hypersensitivity
IgG or IgM mediated
Formed by cell-bound antigen
IgG/IgM Ab binds to cellular antigen, leading to complement activation and cell lysis
Ex. Anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis (Positively charged Ags are planted on the negatively charged GBM, leading to type II hypersensitivity reaction)
Type III hypersensitivity
IgG or IgM mediated
Formed by soluble antibody
Antigen-antibody complexes are deposited in tissues
Complement activation provides inflammatory mediators and recruits neutrophils
Enzymes released from neutrophils damage tissues
Ex. Post streptococcal glomerulonephritis, rheumatoid arthritis, SLE
Xenografts
Exchanged b/w members of different species
Very susceptible to rapid attack by naturally occurring Abs activating complement
Insertion of human genes into genome of donor animal can help
What molecules are released by graft tissues leading to host immune responses and possible hyperacute allograft rejection
Mechanical trauma and ischemia-reperfusion injury (AKI) to graft tissues causes release of DAMPs, triggering the clotting cascade, which leads to increased vascular permeability and neutrophil/monocyte attraction
Also leads to kinin cascade w/bradykinin, causing vasodilation, smooth muscle contraction and further increasing vascular permeability
If these early responses aren’t controlled, you end up with hyperacute allograft rejection
ABO incompatible kidney transplant
Used to be absolute contraindication due to risk of hyperacute rejection
Now with better immunosuppression, ABOi-KT outcome is comparable to ABO compatible
ABO matching is not important for what types of transplantations
Corneal transplant, heart valve transplant, bone and tendon grafts (nonvascularized tissues)
ABO incompatibility is not a contraindication to stem cell transplantation
What Ig reacts with blood type antigens
Most likely IgM because they are carbohydrate antigens
Microcytotoxicity test for pre-existing non-ABO Abs against donor
Recipient serum with Abs is added to donor cells
Complement is added
Dye is added
If dye accumulates in the cells, that means a MAC complex was formed and there are indeed preformed Abs present
The success of transplantation is dependent on matching of
HLA Ags
What HLA class is strongest barrier to transplantation
HLA class I because all nucleated cells express them
Mixed lymphocyte response
Donor cells are radiated so they cannot proliferate but can serve as APCs
Mixed with recipient cells and lymphocytes + H-thymidine
If recipient cells proliferate and radioactive thymidine is seen- HLA class II of recipient does not match donor cells
If no radiation seen/no proliferation - good for transplant
Sequence of events in allograft rejection
APCs trigger CD4/CD8 T cells
Both a 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
