Renal Immunology

Question 1

What is sterile renal inflammation induced by?

Answer 1

Intrinsic DAMPs released by necrotic parenchyma kidney cells due to ECM degradation

Question 2

What do DAMPs (alarmins) represent?

Answer 2

Intracellular molecular structures including HMGB1 (nucleolus protein), uric acid, HSPs (exosomes), S100 protein (cytoplasm), hyaluronans (degradation of the ECM)

Question 3

Why is the kidney susceptible to complement induced damage?

Answer 3

High filtration rate favors tissue deposition of immune complexes

Question 4

Which cells infiltrate renal tissue in response to inflammation?

Answer 4

Neutrophils and monocytes

Question 5

What do neutrophils release in renal tissue in response to inflammation?

Answer 5

Proteases (cause GBM degradation)

Oxygen derived free radicals that cause cell damage

Question 6

After differentiating from monocytes, M1 macrophages will infiltrate the glomeruli and what release inflammatory mediators?

Answer 6

ROS, cytokines, chemokines, growth factors, eicosanoids and NO which contribute to vascular injury and cell proliferation

Question 7

The immune responses during early stage AKI are mediated by what?

Answer 7

Th17 and Th1 cells

Dominate in tissue injury

Question 8

Which cell prevails in late stage AKI?

Answer 8

Th1 cells

Question 9

Which type of macrophage plays a key role in AKI?

Answer 9

M1

Question 10

What is the role of Th17 cells in AKI?

Answer 10

Secrete IL-17 that stimulates resident cells in the kidney to produce proinflammatory cytokines, chemokines and other mediators

Question 11

What role does IL-17 play in AKI?

Answer 11

Induces expression of chemokine CCL20 that primarily leads to the recruitment of neutrophils, monocytes, Th1 and Th17 cells

Question 12

What induces classically activated M1 macrophages?

Answer 12

IFN-gamma from Th1 cells

Question 13

Describe M1 macrophages

Answer 13

Secrete ROS, NO and lysosomal enzymes —> microbicidal actions, phagocytosis, killing of bacteria and fungi
Secretion of IL-1, IL-12 and IL-23 which promote inflammation

Question 14

Describe alternatively activated M2 macrophages

Answer 14

Induced by secretion of IL-13 and IL-4 by Th2 cells
Secrete IL-10 and TGF-beta which are anti inflammatory, promote wound repair and fibrosis
Also inhibit M1 macrophage inflammation

Question 15

What role do Treg cells play in AKI?

Answer 15

Prevent the AKI progression and restrict inflammation

Promote repair and regeneration

Question 16

In AKI complement activation occurs downstream of what?

Answer 16

Immune complex deposition (type III hypersensitivity) or Ab-mediated injury (type II)

Question 17

Describe type II hypersensitivity reactions

Answer 17

IgG or IgM bind to cellular Ags leading to complement activation and cell lysis
Upon tissue damage positively charged Ags can be planted into the negatively charged GBM

Question 18

What are examples of type II hypersensitivity reactions?

Answer 18

Pts with anti GBM Ab mediated GN

Question 19

Describe type III hypersensitivity reactions

Answer 19

Ag-Ab complexes are deposited in tissues
Complement activation provides inflammatory mediators and recruits neutrophils
Enzymes released from neutrophils damage tissue

Question 20

What are examples of type III hypersensitivity reactions?

Answer 20

Post-streptococcal glomerulonephritis, RA and SLE