Lecture 15: Immunological Aspects of Renal System (Part 1) Flashcards
What are some key differences between acute kidney injury and chronic kidney disease?
Acute Kidney Injury
- normally reversible
- increased serum creatinine levels
Chronic Kidney Disease
- kidney damage >3 months
- subtle decrease in function
- can be irreversible
What are some diseases that can increase risk of kidney injury?
Diabetes
Hypertension
Metabolic Syndrome
What is a major cause of acute renal failure and can cause abrupt decrease in kidney function?
Ischemic acute kidney injury (AKI)
- metabolic acidosis
- ATP depletion
- from sterile inflammation
What causes sterile inflammation?
1) DAMPs released from dying parenchymal kidney cells generated during ECM degradation and remodeling
2) DAMPS bind to C-reactive protein (CRP), activating classical complement pathway
3) TLRs activated and induce innate immune responses and renal inflammation
C-reactive proteins have 5 subunits just like ___.
IgM
What are examples of DAMPs/alarmins?
- HMGB1
- Uric Acid
- HSPs (exomes)
- S100 protein
- Hyaluronans in ECM
DAMPs are recognized by _____ which activate _____, expression, leading to release of inflammatory cytokines such as ________
TLRs, NLRs, C-type lectin
NF-KB
TNF alpha, IL-6, IL-1,
What type of DAMPs are released during a necrotic event and what receptors recognize the?
What immune cells are recruited to damaged cell because of this signaling?
HMGB-1 > RAGE receptor
Uric acid > NLRP3 receptor
HSPs > scavenger receptor class A
Dendritic cells, Macrophages and Endothelial cells that induce inflammation
What cells predominates during the early stage of AKI?
What cells predominate during the late stage of AKI?
TH17 > tissue injury
TH1
What type of macrophages differentiate at early stage of AKI?
What does it do after?
M1 (classically activated)
make IL-1, 12, 23, chemokines to induce inflammation
use ROS, NO and lysosomes during phagocytosis
What type of macrophages differentiate after the inflammation is localized?
What does it do?
M2 (alternatively activated by IL4 and IL13 from T cells)
Release IL-10 and TGF-B (anti-inflammatory)
Release Proline, polyamines, TGF-B and PDGF (tissue repair) > myofibroblast activation > actin deposition > can lead to scarring and further tissue damage
What is the role of TH17 cells in the development of AKI?
releases IL-17 > causing renal cell to release CCL20/MIP3 > recruitment of neutrophils, monocytes, TH1 and TH17 to kidney cell > immune mediated kidney damage
What is the role of TRegs in AKI?
Anti inflmmatory mechanisms (IL-10 and TGF B) to achieve peripheral tolerance, induce tissue repair
If Tregs fail, AKI is further induced
Why are kidneys susceptible to complement-induced damage?
Filtration favors tissue deposition of immune complexes
complement usually present in biopsies for AKI diseases
What happens when DAMPs from AKI stimulate the production of C3a and C5a?
these act as chemoattractants: stimulate proinflammatory responses via neutrophils and macrophages
