7. Immunological Aspects of the Renal System

Question 1

Acute renal failure is defined as an abrupt decrease in kidney function which is mainly cause by what?

Answer 1

ischemic Acute kidney injury (AKI), which is common and causes impairment of kidney filtration via metabolic acidosis and ATP depletion

Question 2

Some causes of hypoperfusion to the kidney cause AKI are sepsis (sterile inflammation), decreased effective intravascular volume, medications and?

Answer 2

intravascular volume depletion and hypotension

and renal vascular disease

Question 3

sterile renal inflammation is induced by intrinsic damage-associated molecular patterns (DAMPs) which are released from dying kidney cells and generated during ECM degreadation. C reactive protein CRP can bind damps and do what?

Answer 3

activate complement via the classical pathway.

Immune cells also can recognize damps via TLRs which induce inflammation as well

Question 4

Pamps and damps can be recognized by toll like receptors, nod like receptors and c type lectin which use what cytokines for inflammation? (3)

Answer 4

TNFA
IL6
IL1B

Question 5

When there is trauma to renal tissue, necrosis/apoptosis occurs, dAMP signals bind receptors on resident cells and activate dendritic, macrophage and endothelial cells to start inflamation. Which leads to? (4)

Answer 5

leukocyte activation
cyotkine release
tissue migration
reduced flow

Question 6

In earlier stages of renal damage, Th17 cells predominate but in later stages Th1 cells do. Which macrophages (M1/M2) play a role in AKI and tissue repair?

Answer 6

M1 = acute kidney injury (inflam/phagocytosis)
M2= tissue repair (antiinflam)

Question 7

M1 for AKI are classically activated via pamps and damps through TLRs/PRRs, IFNY promotoe m1 differentiation. How are M2 for tissue repair activated?

Answer 7

M2 is Alternatively activated, induced by IL4/IL13 by a subset of T cells, and M2 are controlled by IL10 and TGFB

Question 8

Th17 cells secrete IL17 that stimulate resident renal cells to produce chemokines and inflammatory mediators- recruits primarily neutrophils. Th17 cells also faciliate infiltration of Th1, Th17 and monocytes by secreting?

Answer 8

CCL20 aka macrophage inflammatory protein 3 (MIP3)

Question 9

Each of the three complement pathways have been linked to kidney disease. When there is damage to kidneys, DAMPs signal to all 3 pathways to make C3 and C5 which activate MAC and?

Answer 9

inflammation, which activate M1/M2 which leads to fibrosis and fibrotic repair

Question 10

In kidney injury, complement activation occurs downstream of immune complex deposition (typeIII) or antibody mediated injury which is?

Answer 10

type II

Question 11

Type II hypersensistivy reactions involve IgG or IgM and cell bound antigen. IgG/M binds to cellular antigen, leading to complement activation and cell lysis. An example of this reaction is?

Answer 11

patients with antiglomerular basement membrane (GBM) antibody mediate GN

Question 12

Type III hypersensitivity involves IgG/M and soluble antigens. The antigen antibody complexes are deposited in tissues. Complement activation increases inflammation and recruits neutrophils, which release enzymes. An example of this reaction? (3)

Answer 12

post-streptococcal glomerulonephritis, rheumatoid arthritis, lupus

Question 13

Kidney transplant is the only treatment for end-stage organ failure, with a barrier to this transplant being genetic compatibility. need to HLA match. What cuases transplant rejection?

Answer 13

host versus graft response, including histocompatitiblity Ags, hyperactue rejection, chronic rejection

(**need immunosuppressive drugs for successful trasnplant)

Question 14

Autografts are grafts exchanged from one part to another part on the same person.
Isografts is exchange between same genetics (identical twin).
Allo grafts are exchange between nonidentical people of the same species
Xenografts is what?

Answer 14

grafts from different species which increases chance of rapid attack by body. inserting human genes into animals helps survival

Question 15

what are the four key concepts in kidney transplantation? 4

Answer 15

1. condition of allograft
2. donor-host antigenic disparity
3. strength of host anti-donor reponse
4. Immunosuppressive regimen

Question 16

When new tissue is transplanted, it sends mediators which leads to tissue damage via:
1. clotting cascade and fibrinopeptides
2. fibrinopeptides increase vascular permeability and attract neutrophils and Mø
3. kinin cascade produces bradykinin which causes vasodilation and increased vascular permaebility
4?

Answer 16

if these proinflammatory responses are uncontrolled, it can result in hyperacute allograft rejection

Question 17

ABO is the major blood group system, and is a barrier to transplantation. Ags to A and B are in individuals without these antigens on their RBCs. What kind of transplants is ABO matching not important for? (3)

Answer 17

corneal transplant
heart valve transplant
bone/tendon grafts

NONVASCULARIZED TISSUES

Question 18

Group AB is the universal acceptor while Group O is the universal donor (any blood takes donated O). What do A and B take?

Answer 18

A takes A or O

B takes B or O

Question 19

When matchin donor and recipient, for which transplants is it not important to test for pre-existing non-ABO Abs such as anti-class I/II HLA abs?

Answer 19

non vascularized tissue transplants- such as corneal heart valves and bone

Question 20

How do preexisting Abs appear?

Answer 20

pregnancy induced HLA sensitization leads to being able to detect anti-HLA class I/II Abs in humans

Question 21

Microcytotoxicity test for preformed Abs has 3 steps.

1. recipient serum with Abs is added to donor cells, binding to them
2. complement is added (MAC), forming pores in the cells
3. ?

Answer 21

3. dye is added and accumulated in cells = preformed Abs are present

Question 22

Successful transplant is dependent on HLA Ags, MHC/HLA class 1 and 2. Compatibility between donor and recipient is required due to the?

Answer 22

extreme polymorphism of HLA

Question 23

class 1 HLA(A and B) are strong barriers to transplantation, the 3 most important for class 2 are?

Answer 23

HLA-DR/DP/DQ

Question 24

The source of lymphocytes for HLA class 1 typing is in the spleed and LN (dead cadaver). HLA antisera are obtained (vaccine) which contains abs to HLA ags. The abs bind to HLA Ag on lymphocytes. the ab-ag complex formed, activates complement and lysis. what does it mean if both the donor and recipient end up with dye inside the cell?

Answer 24

the HLA ag are identical

when the same process is done for both donor and recipient and the donor has dye inside but the recipient does not, then that menas the HLA Ag are NOT identical

MICROCYTOTOXICITY TEST FOR CLASS I HLA

Question 25

When testing for class II HLA compatibility, donors which dont proliferate d/t radiation but can serve as APCS are mixed with recipient cells, add H-thymidine, proliferation occurs and radioactivity is incorporated in DNA that allows cell proliferation. What does this mean in regards to if the donor/recip match?

Answer 25

this result means the recipient cells do not share the same class II MHC as the donor

MIXED LYMPHOCYTE RESPONSE MLR

Question 26

When radiation to donor cells when testing class II HLA is done and added to recipient cells along with H-thymidine radioactivity is NOT incorporated into the DNA if there is NO cell proliferation. The result is no proliferation/radiation in recipient cells so this means?

Answer 26

Recipient cells share the same class II MHC as donor = good for tranplantation

Question 27

What are the 5 event in allograft rejection?

Answer 27

1. APCs trigger CD4 and CD8 T cells
2. Local and systemic Immune response
3. Cytokines recruit/activate immune cells
4. specific T cells, NK cells, Mø for mediated cytotoxicity
5. Allograft rejection

Question 28

Host versus graft disease is when a kidney is transplanted and the recipients T cells attack the transplant while graft versus host diesase is when?

Answer 28

When bone marrow is transplanted, the T cells in the transplant attack the recipients tissues

Question 29

Host v graft is an adaptive immune response, much more strong and vigorous than response against pathogen. Why is this?

Answer 29

there is a higher frequency of T cells (1/100) which respond to allogeneic APCs (graft) as compared to 1/100000 T cells that respond to a virus

Question 30

What is important to remember about immune memory of previous encounters with the donors Ags?

Answer 30

the SECOND graft from the same donor is rejected MORE rapidly

Question 31

During direct allorecognition, T cells recognize intact allogeneic MHC molecules on the surface of donor APCs in the graft. In indirect allorecognition?

Answer 31

alloantigens are recognized in the context of recipient MHC class II molecules after they have been processed and presented by recipient APCs

Question 32

Host V Graft: injury via DAMPs activate endothelial cells and T cells enter the allograft which interact with APC and become stimulated which causes inflammation and further activation. what are the humoral and cellular mechanisms for graft rejection?

Answer 32

humoral rejection via Th2 (IL4 IL5 IL10)

cellular rejection via Th1 (IL2, IFNY)

Question 33

H vs G hyperacute rejection occurs immediately due to TYPE II hypersensitivity. the mechanism is that there are preformed antibodies directed against the donor tissue caused by?

Answer 33

accidental ABO blood type incompatability, presents in surgery with thrombosis and occlusion of graft vessels

***RARE

Question 34

H vs G acute rejection occurs weeks to months via type IV hypersensitivity. T cell mediated immune response is directed against the foreign MHC, resulting in?

Answer 34

inflammation and leukocyte infilitration of graft vessels

**MOST COMMON

via CD4/CD8

Question 35

H vs. G chronic rejection occurs months to years via type IV hypersensitivity. T cell mediated process resulting from the foreign MHC ‘looking like’ a self MHC carrying an Ag. resulting in?

Answer 35

intimal thickening and fibrosis of graft vessels as well as graft atrophy

**ischemia causes occlusion of blood = macrophages attack

Question 36

What are the times and types of hypersensitivity reactions for the following?
Hyperacute
Acute
Chronic

Answer 36

H: immediately, Type II
A: weeks to months, type IV
C: months to years, Type IV

Question 37

Graft vs Host disease (GVHD) is caused by reaction of grafted mature T cells in the marrow with allo-ags of the host, occuring more in what type of recipients?

Answer 37

immunocompromised

***occurs most in small bowel, lung, or liver

Question 38

Acute GVHD is when epithelia cell death occurs in the skin, liver and GI. clincally presents as?

Answer 38

rash, jaundice, diarrhea, and GI hemmorhage

Question 39

Chronic GVHD is when there is fibrosis and atrophy of the affected organ, presents as?

Answer 39

complete dysfunction of the affect organ, obliterating small airways

Question 40

GVHD onset varies and it is a type IV hypersensitivity. Donor t cells in the graft proliferate and attack the recipients tissue. most commonly seen in____ and presents with? (3)

Answer 40

bone marrow transplants

presents with diarrhea, rash and jaundice

Question 41

what are the two different ways the graft attacks and kills recipient tissue?

Answer 41

either via Fas-Fas-L or Perforin/Granzyme, both resulting in apoptosis of recipient cell