Lecture 14: Immunological Aspects of Renal System (Part 1)

Question 1

What are some key differences between acute kidney injury and chronic kidney disease?

Answer 1

Acute Kidney Injury

• normally reversible
• increased serum creatinine levels

Chronic Kidney Disease

• kidney damage >3 months
• subtle decrease in function
• can be irreversible

Question 2

What are some diseases that can increase risk of kidney injury?

Answer 2

Diabetes
Hypertension
Metabolic Syndrome

Question 3

What is a major cause of acute renal failure and can cause abrupt decrease in kidney function?

Answer 3

Ischemic acute kidney injury (AKI)

• metabolic acidosis
• ATP depletion
• from sterile inflammation

Question 4

What causes sterile inflammation?

Answer 4

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

Question 5

C-reactive proteins have 5 subunits just like ___.

Answer 5

IgM

Question 6

What are examples of DAMPs?

Answer 6

• HMGB1
• Uric Acid
• HSPs (exomes)
• S100 protein
• Hyaluronans in ECM

Question 7

DAMPs activate _____, releasing inflammatory cytokines such as TNF alpha, IL-6, IL-1, and etc.

Answer 7

NF-kB

Question 8

Damage to renal tissue can cause necrosis, releasing DAMPs. DAMPs are recognized by PRR and can activate what immune cells?

Answer 8

Dendritic Cells
Macrophages
Endothelial Cells

Question 9

Dendritic cells can cause what?

Answer 9

Acute Kidney Injury and Infections

Question 10

Macrophages can cause what?

Answer 10

Most kidney diseases

Question 11

Endothelial cells can release specific cytokines and cause what?

Answer 11

Ischemia-induced glomerulonephritis

Diabetes

Question 12

In early stages of acute kidney injury, what type of cells mediate the immune response?

Answer 12

Th17

-attracts both innate and adaptive immune cells

Question 13

In late stages of acute kidney injury, what type of cells mediate the immune response?

Answer 13

Th1

Question 14

What cytokines are main activator of pro-inflammatory macrophages?

Answer 14

IFN-gamma and TLR-ligands

Question 15

What cytokines are main activator of anti-inflammatory macrophages?

Answer 15

IL-13 and IL-4

Question 16

What do M1 macrophages do?

Answer 16

Perpetuate acute phase of inflammation in kidney

Question 17

What do M2 macrophages do?

Answer 17

Important in tissue repair and renal fibrosis

-controlled by IL-10 and TGF-β

Question 18

Describe myofibroblasts and renal tissue repair.

Answer 18

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

Question 19

Th17 cells secrete IL-17 that primarily leads to the recruitment of what?

Answer 19

Neutrophils via expression of CCL20

Question 20

Th17 cells facilitate infiltration of what cells that lead to ?

Answer 20

Monocytes, Th1, Th17

-immune mediated kidney damage

Question 21

What is the role of Treg cells in acute kidney damage?

Answer 21

Treg cells release IL-10 and TGF-β

• promote peripheral tolerance
• inhibit pro-inflammatory cells
• promote kidney tissue repair

Question 22

Why are kidneys susceptible to complement-induced damage?

Answer 22

Filtration favors tissue deposition of immune complexes

Question 23

What happens with the production of C3a and C5a?

Answer 23

Chemoattractants: stimulate proinflammatory responses via neutrophils and macrophages

Question 24

What happens with the production of C3b and C5b?

Answer 24

Deposit in tissues and promote production of MAC complex, leading to cell death

Question 25

Describe type II hypersensitivity type.

Answer 25

• 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.

Question 26

Describe type III hypersensitivity type.

Answer 26

• Antigen form: soluble antigen
• Activation: antigen-antibody complex deposited in tissues
• Response: Complement activation –> inflammatory mediators –> neutrophils
• Example: Post-streptococcal glomerulonephritis, RA, lupus