Renal Inflammation Flashcards
What is the functional criteria of Acute Kidney Injury?
Increase in serum creatine by 50% within 7 days
or
Increase in serum creatine by 0.3 mg/dl within 2 days
or
Oliguria
What are the causes of AKI?
Hypoxia inducing illnesses
Intravascuplar Volume Depletion and Hypotension
Decreased Effective Intravascular volume
Hepatorenal syndrome
Sepsis
Renal vascular disease
What is the major cause of acute renal failure?
Ischemic acute kidney injury leading to metabolic acidosis and ATP depletion
How are DAMPs released?
Released from parachymal kidney cells during ECM degredation
What binds DAMPS and activates the classical complement pathway?
C-reactive Proteins
How do DAMPS induce innate immune response and renal inflammation?
Binding to toll-like receptors
What are the examples of DAMPS discussed?
HMGB1
Uric Acid
HSPs (Exosomes)
S100 protein (cytoplasm)
Hylauronans in ECM
What cell is activated during acute kidney injuries and infections?
Dendritic Cells
What cell is activated during IC-GN, diabetes, and sepsis?
Endothelial cells
What to endothelial cells release as part of an inflammatory response?
TNF, IL-6, Chemokines, and IFNa
What are the pattern recognition receptors discussed?
Toll-like
NOD like
C-type lectin
What do M2 cells release as part of the anti-inflammatory response?
What is the overall function of an M2 cell?
Arginase-I
IL-10
Clearance of apoptotic cells
What activates a classically activated M1?
PAMPS and DAMPS through binding of TLR and other PRRs
IFN-y also promotes differentiation
What factors reprogram an M2 cell?
CSF-1 (M-CSF)
IL-10
What induces M2 activation?
IL-4 and IL-13
What substances are secreted by M1 macrophages for microbicidal purposes.
ROS, NO, and lysosomal enzymes
What substances are secreted by M2 macrophages in wound repair?
Proline
Polyamides
TGF-B
What cells assist in the generation of myofibroblasts and production of ECM during wound repair?
Pericytes
What stimulates differentiation of a Naive CD4+ T cell into the following:
IL-12
IL-4
IL-6
Th1
Th2
Th17
The “chemokine pattern” that plays a roll in recruitment of neutrophils is released by what cells?
Meangial and tubular epithelial cells
These have been influenced by IL-17 secreted by Th17.
What does CCL20 or MIP-3 do?
Stimulates the infiltration of monocytes, Th1, and Th17 cells
What are they key regulators of the inflammatory response?
What do they secrete?
TREG Cells
TGF-B and IL-10
Type II hypersensitivity reactions are caused by what mechanism?
Example?
IgG or IgM is bound to cellular antigen, triggering complement pathway.
Anti-glomerular basement membrane mediated glomerular nephritis
Which hypersensitivity pathway is involved in neutrophil recruitment triggered by antigen-antibody complexes?
Type III
What are the key concepts influencing transplantation?
Donor-host antigenic disparity
Immunosupressive regime
Condition of allograft
Strength of host anti-donor response
What peptides increase local vascular permeability and serve as a chemoatractant for neutrophils and macrophages?
Fibren peptides
What substance results from the kinin cascade?
What does this substance do?
Bradykinin
Vasodilation
What transplantations are not sensitive to donor differences in ABO blood type or Class I/II HLA abs.
Corneal
Heart valves
Bone and tendon grafts
How is microcytotoxicity test for performed Abs performed?
Recipeint serum added to donor cells
Complement then added
Dye is then added
The if the Abs bount to an antigen on the donor cells, they will have induced the complement system, making the cells porous. These porous cells should retain the added dye.
What are the class I antibodies that are strong barriers to transplantation?
HLA-A and HLA-B
What are the most important class II HLA ags in transplantation?
HLA-DR
HLA-DQ
HLA-DP
What is measured to determine Class II HLA compatibility?
What substance allows for this to be measured?
Proliferation of recipeint cells
Labled with 3H-thymididine
If there is no proliferation of lymphocytes you can transplant
What substances are release when humeral rejection occurs?
What cells release these?
IL-4, IL-5, IL 10
Th2
Which form of allorecognition occures whe MHC II molecules that have been processed and presented by APCs trigger an immune response?
Indirect allorecognition
At what time does the following rejections occur?
Hyperacute
Acute
Chronic
Immediately (within minutes)
Acute (days to weeks)
Chronic (months to years)
Acute rejection results in what pathology?
Inflammation and leukocyte infiltration of the grafted vessels
Parenchymal cell damage and interstitial inflammation
What are the non-immunological factors that influence this Chronic host vs graft rejection?
Ischemia-reperfusion damage
Recurrence of disease that causes failure of the kidneys
Nephrotoxic drugs (cyclosporine A)
What causes a Graft-versus-host response?
Reaction of grafted mature T cells of bone marrow with all antigens of the host.
Directed against minor HLA Ags of the recipient
What are the symptomes of Acute Graft versus Host Disease (GVHD)?
Rash
Jaundice
Diarrhea
GI Hemorrhage
