Lecture 14: 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?
- HMGB1
- Uric Acid
- HSPs (exomes)
- S100 protein
- Hyaluronans in ECM
DAMPs activate _____, releasing inflammatory cytokines such as TNF alpha, IL-6, IL-1, and etc.
NF-kB
Damage to renal tissue can cause necrosis, releasing DAMPs. DAMPs are recognized by PRR and can activate what immune cells?
Dendritic Cells
Macrophages
Endothelial Cells
Dendritic cells can cause what?
Acute Kidney Injury and Infections
Macrophages can cause what?
Most kidney diseases
Endothelial cells can release specific cytokines and cause what?
Ischemia-induced glomerulonephritis
Diabetes
In early stages of acute kidney injury, what type of cells mediate the immune response?
Th17
-attracts both innate and adaptive immune cells
In late stages of acute kidney injury, what type of cells mediate the immune response?
Th1
What cytokines are main activator of pro-inflammatory macrophages?
IFN-gamma and TLR-ligands
What cytokines are main activator of anti-inflammatory macrophages?
IL-13 and IL-4
What do M1 macrophages do?
Perpetuate acute phase of inflammation in kidney
What do M2 macrophages do?
Important in tissue repair and renal fibrosis
-controlled by IL-10 and TGF-β
Describe myofibroblasts and renal tissue repair.
M2 macrophages promote pericyte accumulation and activation for myofibroblast differentiation. Unlike fibroblasts, myofibroblasts has actin.
- can lead to scarring with accumulation
- useful marker for kidney diseases
Th17 cells secrete IL-17 that primarily leads to the recruitment of what?
Neutrophils via expression of CCL20
Th17 cells facilitate infiltration of what cells that lead to ?
Monocytes, Th1, Th17
-immune mediated kidney damage
What is the role of Treg cells in acute kidney damage?
Treg cells release IL-10 and TGF-β
- promote peripheral tolerance
- inhibit pro-inflammatory cells
- promote kidney tissue repair
Why are kidneys susceptible to complement-induced damage?
Filtration favors tissue deposition of immune complexes
What happens with the production of C3a and C5a?
Chemoattractants: stimulate proinflammatory responses via neutrophils and macrophages
What happens with the production of C3b and C5b?
Deposit in tissues and promote production of MAC complex, leading to cell death
Describe type II hypersensitivity type.
- Antigen form: cell-bound antigen
- Activation: cell-bound antigen bound to IgM/IgG
- Response: Complement activation and cell lysis
- Example: Patients w/ anti-glomerular basement membrane will have antibodies for this.
Describe type III hypersensitivity type.
- Antigen form: soluble antigen
- Activation: antigen-antibody complex deposited in tissues
- Response: Complement activation –> inflammatory mediators –> neutrophils
- Example: Post-streptococcal glomerulonephritis, RA, lupus
