Renal Immuno Flashcards
How do you define AKI
Rapid decrease in kidney function as measured by an increase in serum creatinine
Impairment of kidney filtration is activated by ______________ in vascular and tubular cells
ATP depletion
What are the causes of kidney hypoperfusion
Sepsis, medications, decreased effective circulating volume, hypotension, hepatorenal syndrome
Kidney injury that doesn’t heal correctly can lead to
Renal tissue fibrosis
Why is kidney damage hard to track
Often not identified until 60-70% of kidney has been damaged beyond repair
What is the main cause of kidney injury that we look at
Ischemia
What is the general inflammation cascade
- Ischemic event
- Cytokine release
- Expression of adhesion molecules
- Increased permeability
What happens to small arterioles in post-ischemic kidney disease
They vasoconstrict due to decreased production of NO
What are the inflammatory cytokines that we are looking at
TNFα, IL-1β, IL-6, IL-12, IL-15, IL-18
Besides inflammation, what else does small vessel occlusion lead to
Activation of the coagulation system
What are the main end-effects of ischemic AKI
- Reduced GFR
- High FE_Na
- Concentrating defects
What is the main signal of sterile inflammation
Release of DAMPs or ALARMINS
What are the main DAMPs released by parenchymal cells
HMGB1 (nucleolus), uric acid, HSPs (heat shock proteins from exosomes), Hyaluronans in ECM, S100 protein in cytoplasm
What are DAMPs recognized by? What does this activate
TLR; NF-κB
What TLR recognizes DAMPs
TLR-4
What cells in the inflammation process migrate to LN
Dendritic cells
What do dendritic cells function in
Acute kidney injury and infections
What is the function of macrophages in acute kidney injury
Continue to present signals to T cells to keep them active
What induces M1 macrophages
PAMPs/DAMPs, IFN-γ
What type of macrophages are in charge of the acute phase
M1
What do M1 macrophages primarily produce
ROS, NO, lysosomal enzymes, IL-1, IL-12, IL-23
What induces M2 macrophages
IL-13 and IL-4
What do M2 macrophages produce
TGFβ and IL-10
What does TGFβ do
Serves as a chemotractant for repair cells (fibroblasts)
What cells predominate in the M1 response
Neutrophil, NK cell, Th1/17
What cells predominate in the M2 response
Th2 and Treg
What does the severity of the immune response depend on?
The ratio of M1:M2 cells that respond
What has shown the best results as a renal disease inhibitor
Complement inhibitors; anti-C5
Deficiency of what has protected mice from ischemic injuries? What worked the best
C3a receptor or C5a receptor; C5a receptor
How do we determine degree of complement activation
changes in level of C3 and C4 in blood (C3 being highest); C3a and C5a in the urine or plasma
What type of cells are rarely found in healthy kidney tissue
Mast cells
What are the main causes of fibrosis in kidneys
TGFβ and Ang II
What can also generate Ang II besides ACE
Chymase
What participate in tissue remodeling
Tryptase, chymase, and carboxypeptidase A
What influences T cells to become Th1
IL-12
What influences T cells to become Th2
IL-4
What influences T cells to become Treg
TGFβ
What influences T cells to become Th17
TGFβ and IL-6
What do Th1 cells produce
IFNγ and T-bet
What do Th2 cells produce
IL-4 and GATA3
What do Tregs produce
TGFβ and FoxP3
What do Th17 cells produce
IL-17 and RORγT
Early stages of the adaptive immune response are mediated by
Th17
At later stages of the adaptive immune response, what cells are prevailing
Th1
What do Th1 produce and what do they activate
IFNγ; resident macrophages
The outcome of the inflammatory disease depends on
The balance between pro- and anti-inflammatory immune cells
What recruits neutrophils
IL-17
What do Th17 produce that recruits monocytes and Th1 cells
CCL20
What switches M1 macrophages to M2
Treg
Type II hypersensitivity is what
Ab against tissue Ags and complement
What are type III hypersensitivities
Soluble Ag-Ab complexes
What can increase the likelihood of successful xenografts
Inserting human genes
When is ABO matching not important
Non-vascularized tissues
- corneal transplants
- heart valve transplantation
- bone and tendon grafts
ABO incompatibility is/isn’t important in stem cell transplants
Isn’t
What is the universal recipient
AB; they have no AB in their blood
What is the universal donor
O; they don’t have an Ag present
Why are class 1 HLA so important for transplantation
All cells have type 1
What cells don’t express type 1 HLA
RBC and platelets
What makes it difficult for a mother to receive transplant from her kids
Pregnancy has induced HLA sensitization
How do we test HLA 1? 2?
Measure intracellular dye after exposing them to different ABs in serum; proliferation of cells
What causes direct allorecognition? Indirect?
Donor dendritic cells activate host T cells and you get direct CTL killing; recipient DC samples graft and activates response and you get Ab and inflammatory cytokines
Direct rejection v. Indirect
Direct - CTL
Indirect - CD4+ and Ab
What causes humoral rejection
Th2
What causes cellular rejection
Th1
What causes hyperacute rejection? Accelerated? Acute? Chronic?
Preformed Ab and complement; reactivation of sensitized T cells; primary activation of T cells; immunologic and non-immunologic factors alike
How are host v. graft carried out
FasL and Fas; binding of perforin and granzyme
What is graft v. host disease
Donor APC activate donor CD8
