14- Immunological Aspects of Renal System Flashcards
This means the kidney has no structural damage, and the functional criteria includes GFR ≥ 60 mL/min per 1.73 m2. Serum Creatinine is stable.
No Kidney Disease (NKD)
This disease has no structural criteria. The functional criteria includes an increase in SCr by 50% within 7 days, OR an increase in SCr by 0.3 mg/dL within 2 days, OR Oliguria.
Acute Kidney Injury (AKI)
This disease has structural criteria of kidney damage for >3 months. The functional criteria includes GFR <60 mL/min per 1.73 m2 for >3 months.
Chronic Kidney Disease (CKD)
The kidneys are the major filtering organ. They represent only 0.5% of the human body mass, and receive ______ of the total cardiac output (about 1 L/min).
20%
An ischemic acute kidney injury (AKI) leading to metabolic acidosis and ATP depletion is one of the major causes of…
Acute Renal Failure (ARF)
This is classically defined as an abrupt decrease in kidney function.
ARF
In most cases the cause of AKI is not an infection but rather a…
Sterile Inflammation
What do the following lead to?
- Intravascular volume depletion and hypotension
- Hepatorenal syndrome
- Decreased effective intravascular volume
- Medications
- Sepsis
- Renal Vascular Disease
Hypoxia
***Hypoxia then leads to AKI
Sterile renal inflammation is induced by ________, which are released from dying parenchymal kidney cells and generated during ECM degradation and remodeling.
DAMPs
Native ________ has five subunits like IgM. It can bind DAMPs and activate complement via the classical pathway.
CRP (C-reactive protein)
Immune cells can recognize DAMPs via ______ ______, become activated, and induce innate immune responses and renal inflammation.
Toll-like receptors
This type of DAMP is a protein passively released during necrosis and recognized by RAGE.
HMGB1
This type of DAMP is another diffusible danger signal recognized by NLRP3.
Uric Acid
This type of DAMP is another danger signal recognized by scavenger receptor class A.
HSPs
All DAMPs activate _________ pathway and release of inflammatory cytokines.
NF-kB
In the early stages of AKI, immune responses are mediated by pro-inflammatory _______ cells. These dominate in tissue injury.
Th17
_______ macrophages play a key role in AKI (pro-inflammatory), while _______ macrophages play a key role in tissue repair (anti-inflammatory).
M1
M2
In the late stage of AKI, the pro-inflammatory _______ cells prevail.
Th1
Classically activated _______ _______ are induced by PAMPs and DAMPs through binding to TLRs and other PRRs.
M1 Macrophages
_______ are pro-inflammatory cytokines that promote differentiation of M1 Macrophages.
IFN-y
Alternatively activated ________ ________ are induced by IL-4 and IL-13 produced by certain subsets of T cells.
M2 Macrophages
M2 Macrophages are important in tissue repair and renal fibrosis which both are controlled by ______ and ______.
IL-10
TGF-B
Accumulated Th17 cells secrete _______ that stimulates resident renal cells to produce inflammatory mediators, aka cytokines, chemokines, and other mediators.
IL-17
IL-17 induces expression of chemokine _______ that primarily leads to the recruitment of neutrophils.
CCL20
Th17 cells facilitate infiltration of monocytes, Th1 cells, and Th17 cells directly by secretion of the CCL20. This is also called _________. Recruitment of other pro-inflammatory leukocyte subsets ultimately leads to the progression of immune-mediated kidney damage.
MIP-3 (Macrophage Inflammatory Protein-3)
Complement proteins are seen in biopsies from patients with virtually all forms of __________, and each of the three activation pathways have been linked with various kidney diseases.
Glomerulonephritis
The reason for the kidney’s unique susceptibility to complement-induced damage is that _________ favors tissue deposition of immune complexes.
Filtration
AKI and tissue damage leads to excessive generation of DAMPs which activate resident immune cells via PRRs. Activation of the complement cascade leads to C3b and C5b deposition in the tissue and production of C3a and C5a. The engagement of C3aR and C5aR receptors for C3a and C5a leads to further activation of tissue resident cells. Deposition of _______ leads to massive cell death.
MAC (Membrane Attack Complex)
Tissue damage and inflammation induces accumulation of…
Neutrophils
Monocytes – differentiate into inflammatory Macrophages
C5a and C3a stimulate pro-inflammatory responses in neutrophils and Macrophages. Inflammation causes ________ of kidney cells. At the resolution stage, Macrophages acquire _______ phenotype and control tissue repair and _________.
Necrosis
M2
Fibrosis
T/F. In kidney injury, complement activation may occur downstream of immune complex deposition (type III) or antibody-mediated injury (type II).
True
Kidney _________ is used in the end-stage renal disease.
Transplantation
The barrier to transplantation is the genetic incompatibility of donor and recipient. Today, successful organ transplantation depends on the use of…
Immunosuppressive drugs
_______ matching is one of the methods (immunosuppression is another) for preventing graft rejection. Histocompatibility Ags are the targets for rejection.
HLA
Host versus graft disease causes transplant rejection via mechanisms of what?
Hyperacute Rejection
Acute Rejection
Choric Rejection
This type of rejection is immediate and caused by antibody.
Hyperacute Rejection
This type of rejection occurs days to weeks after transplantation and is caused by T cells (Abs?).
Acute Rejection
This type of rejection is seen months or years after transplantation and caused by vascular trauma, inflammatory products of T cells, Abs.
Chronic Rejection
Graft versus host disease (GVHD) is caused by a reaction of donor immune cells against host tissues. The mechanism of GVHD can be ________ or ________.
Acute
Chronic
This type of graft is exchanged from one part to another part of the same individual.
Autografts
This type of graft is exchanged between different individuals of identical genetic constitutions (i.e., identical twins).
Isografts
This type of graft is exchanged between nonidentical members of the same species.
Allografts (Allogeneic)
This type of graft is exchanged between members of different species.
Xenografts (Xenogeneic)
Xenografts are very susceptible to rapid attack by naturally occurring Abs that cause activation of complement. The insertion of human ________ into the genomes of the donor animals increases the chances of successful transplantation.
Genes
______ incompatible kidney transplantation was previously considered to be an absolute contraindication for patients with end-stage kidney disease due to hyperacute rejection related to blood type barrier.
ABO
***Called ABOi-KT
ABO matching is not important for what type of transplants because they’re non-vascularized?
- Corneal transplantation
- Heart valve transplantation
- Bone and tendon grafts
What Ags are present in all the blood types?
Blood Type A = A Ags
Blood Type B = B Ags
Blood Type AB = A and B Ags
Blood Type O = No Ags
What Abs are present in all the blood types?
Blood Type A = Anti-B
Blood Type B = Anti-A
Blood Type AB = No Abs
Blood Type O = Anti-A and Anti-B
What blood types can type A receive?
A or O
What blood types can type B receive?
B or O
What blood types can type AB receive?
A, B, AB, or O
What blood types can type O receive?
O
Who are the universal donor and universal recipient?
Donor = O Recipient = AB
How do we test for pre-existing non-ABO Abs?
Test is called Microcytotoxicity Test for Preformed Abs
Step 1 = Recipient serum with Abs is added to donor cells
Step 2 = Complement is added
Step 3 = Dye is added
Step 4 = Preformed Abs are present
The success of transplantation is dependent on matching of the _______ Ags. These Ags are encoded by the major histocompatibility complex, _________ and _________.
HLA
HLA Class-I
HLA Class-II
Maternal and paternal HLA Ags are co-dominantly expressed. Each person has six HLA class I alleles (3 maternal and 3 paternal) and six HLA class II alleles (3 maternal and 3 paternal). The _________ Ags are the strongest barriers to transplantation because all nucleated cells express them. The _________ Ags are expressed by professional APCs only.
HLA Class-I
HLA Class-II
How do we test for Class I HLA compatibility in donor and recipients?
Step 1 = Abs are added
Step 2 = Complement is added
Step 3 = Dye is added
Step 4 = If dye accumulates in both donor and recipient cells, then the HLA are identical. If dye only accumulates in donor cell, then HLA are nonidentical.
How do we test for Class II HLA compatibility?
Donor cells are introduced to radioactivity and mixed with recipient cells. +3H-thymidine is added, and if proliferation of recipient cells occurs then radioactivity is incorporated in the DNA. If no proliferation, then there is radioactivity in DNA.
***Called Mixed Lymphocyte Response (MLR)
What are the immune events in allograft rejection?
1) APCs trigger CD4+ and CD8+ T cells
2) Both a local and systemic immune response develop
3) Cytokines recruit and activate immune cells
4) Development of specific T cells, NK cells, or Macrophage-mediated cytotoxicity
5) Allograft rejection
What are the 2 types of immune responses in transplantation?
Host vs. Graft Disease = When a kidney is transplanted and the recipient’s T cells attack the transplant
Graft vs. Host Disease = When bone marrow is transplanted the T cells in the transplant attack the recipient’s tissues
For Host vs. Graft responses, the immune memory of previous encounters with donor Ags is important. From animal experiments, if a second graft is performed from the same donor, then it is rejected more (RAPIDLY/SLOWLY).
Rapidly
During (DIRECT/INDIRECT) allorecognition, T cells recognize intact allogeneic MHC molecules on the surface of donor APCs in the graft.
Direct
During (DIRECT/INDIRECT) allorecognition, alloantigens are recognized in the context of recipient’s MHC class II molecules after they have been processed and presented by recipient APCs.
Indirect
Effector mechanisms of graft rejection are…
Humoral rejection Th2 (IL-4, IL-5, and IL-10)
Cellular rejection Th1 (IL-2, IFN-y)
