Lecture 4: Immunological Aspects of the Renal System Flashcards Preview

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Flashcards in Lecture 4: Immunological Aspects of the Renal System Deck (73)
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1

Impairment of kidney filtration is activated by the depletion of?

ATP in vascular and tubular cells

2

Ischemia reperfusion injury results from a generalized or local impairment in?

Oxygen and nutrient delivery to, and waste product removal from cell of the kidney

3

What occurs to tubular epithelial cells as a result of the imbalance caused by impaired oxygen and nutrient delivery?

Death by apoptosis (clean) and necrosis (dirty death = inflammation)

4

When endothelium is injured what occurs to the small arterioles in post-ischemic kidney; what amplifies this?

Vasoconstrict more than do vessels from normal kidney; amplified by reduced production of NO and other vasodilatory substances by the damaged endothelial cell

5

Which inflammatory cytokines amplify the vasoconstriction of the small arterioles; generated how??

TNF-alpha, IL-1B, IL-6, IL-12, IL-15, and IL-18; result of leukocyte-endothelial adhesion and leukocyte activation

6

The small vessel occlusion and activation of the coagulation system cause what defective functions of the kidney seen in AKI?

- Reduced GFR

- High FENa

- Concentrating defect

7

What is one of the major causes of ARF?

Ischemic acute kidney injury

8

Sterile renal inflammation is induced by what, released from who?

Induced by DAMPs; released from dying parenchymal cells

9

What are the DAMPs released by dying parenchymal cells?

- HMGB1 (nucleolus)
- Uric acid
- HSPs (exosomes)
- Hyaluronans in ECM
- S100 protein in cytoplasm

10

What happens upon the release of DAMPs?

Immune cells respond to DAMps and induce innate immune responses and subsequent renal inflammation

11

Which TLR is activated by DAMP's and what occurs?

TLR-4 causing release of NF-kB in turn increasing production of proinflammatory cytokines and adhesion molecules, which elicits a strong inflammatory response

12

How does apoptosis and necrosis differ in the outcomes seen in AKI?

- Necrosis is the only way DAMPs are released which increased the chance of fibrotic tissue during recovery

- Apoptosis related damage is important for repair

13

Role of dendritic cells in AKI; cytokines released?

- Regulation of adaptive immune response

- They are APC's, migrate to lymph nodes, and present to T cells; can release Type I IFNs, CXCL2, IL-1B and IL-12.

14

Role of macrophages in most kidney diseases?

- Regulation of inflammation and fibrosis

- Remain in the tissue of the kidney and secrete ROS, IL-1B, TNF-alpha, IL-6 and chemokines

15

Macrophages are able to be activated into which two types by what?

M1 - by PAMPs and DAMPs binding to TLR's. IFN-y and other proinflammatory cytokines promote differentiation of M1. M1 then produces cytokine causing more inflammation

M2 - induced by IL-4 and IL-13 produced by TH2 cells. M2 are important in tissue repair and renal fibrosis, both controlled by IL-10 and TGF-B

16

What is the importance of TGF-B?

Released by M2 and is very important growth factor for fibroblasts (chemoattractant)

17

What is ratio of M1/M2 seen in AKI?

- M1 will be acting first as neutrophils, NK cells, TH1 and TH17 cells are releasing INF-Y, inflammation will be further exacerbated

- TH2 and Treg cells will promote the differentiation into M2 cells which will predominate and produce anti-inflammatory effects + tissue repair

18

What is ratio of M1/M2 in CKD?

Due to progressive injury and persistent inflammation, M1's will persist, and this persistent inflammation and fibrotic factors will promote renal fibrosis.

*Products of M1 and M2 are mutually inhibitory, so if M1 is activated, this is inhibiting M2.

19

Explain how we know complement plays an important role in disease of the kidney; which receptor is the best target?

- Animal models lacking C3, C5, and C6 are protected from renal IRI.

- Deficiency of C3a receptor or C5aR protected mice from IRI, but C5aR were most protected

20

How do nephrologists determine activation of complement in a given patient?

- Deposition of complement proteins within kidney

- Disturbances of the level of C3 and C4 in the blood

- Detection of C3a and C5a complement activation fragments in the plasma or urine

- Association of mutations and polymorphisms in complement protein with the development of kidney disease

21

C3a and C5a stimulate chemotaxis of which kind of cell; participates in?

Mast cells increasing by as much as 60x and participate in kidney fibrosis

22

What starts the adaptive immune response?

DC's activate naive CD4+ T cells in the lymph nodes

23

Which cytokines and transcriptional factors cause differentiation into TH1, TH2, Treg, and TH17 cells?

TH1: IL-12 and T-bet

TH2: IL-4 and GATA3

Treg: TGF-B and FOXP3

TH17: TGF-B, IL-6 and RORyT

24

During the adaptive immune response which T cells predominate in the early stages vs later stages?

Early stages: Th17

Later stages: Th1

25

Resident macrophages are activated by?

IFN-y (Th1)

26

Treg cells produce which cytokine and protects against?

Produce IL-10 and are recruited to protect against overwhelming Th1 cell and Th17 cell-mediated immune responses

27

The clinical outcome of kidney disease mainly depends on?

The balance between pro-inflammatory and anti-inflammatory immune cell

28

Th17 cells infiltrating early in the immune response secrete what, which stimulates?

Secrete IL-17 which stimulates resident renal cells to produce chemokines and other inflammatory mediators

29

IL-17 causes the recruitment of ?

Neutrophils

30

What is produced by Th17 cells that recruits monocytes and Th1 cells?

CCL20