Immunology Flashcards
What typically causes impairment of kidney filtration?
ATP depletion
What are the funtional criteria for AKI?
Increase Serum creatinine by 50% within 7 days OR Increase in Serum Creatinine by 0.3 mg/dL within 2 days OR oliguria (small amount of urine production)
Acute inflammation is occurring
What are the functional criteria for CKD?
GFR <60 mL/min for more than 3 months
Irreversible fibrosis is occurring
What is another name for kidney failure?
End stage renal failure
In most cases, what does not cause AKI?
Infection, rather it is typically sterile inflammation
Ultimately, the cause of Kidney hypoperfusion and AKI is what?
Hypoxia, can be caused by many different conditions
- Intravascular volume depletion
- Effective intravascular volume depletion
- Hepatorenal syndrome (liver failure, kidney takes in liver toxins)
- Sepsis
- Medications
- Renal Vascular Disease
What induces sterile renal inflammation?
Intrinsic Damage-Associated Molecular Patterns (DAMPS) released from dying parenchymal (functional) kidney cells
How does the immune response occur after DAMPs are present?
C Reactive Protein (CRP) binds DAMPs and activates the complement via classical pathway
OR
Immune cells recognize DAMPs via Toll-like receptors (TLRs), become activated, and induce innate immune responses and renal inflammation
What mediators are activated once DAMPs/PAMPs are recognized?
TNF(alpha)
IL-6
IL-1(beta)
and others
What signals tell a Macrophage to activate into its M1 form and what does an M1 cell do?
PAMPs and DAMPs induce M1 differentiation through binding to TLRs and PRRs
IFN-(gamma) promotes differentiation into M1 macrophage
M1 macrophage causes inflammation and development of Acute Kidney Injury by increasing IL-1, IL-12, IL-23,a nd other chemokines
What signals tell a Macrophage to activate into its M2 form and what does an M2 cell do?
IL-4 and IL-13 (produced by certain T cells) are responsible for promoting differentiation into M2 macrophages.
M2 macrophages are anti-inflammatory and are responsible for wound repair and fibrosis
M2 cells produce IL-10 and TGF-(beta) which provide anti-inflammatory effects
What cell and signal are responsible for tissue inflammation?
Naive CD4+ T cell becomes an activated T cell.
Activated T cell then differentiates into TH17 cell due presence of TGF-(beta) and IL-6
TH17 cells produce IL-17, which causes inflammation
How do TH17 cells produce inflammation?
TH17 cells infiltrate renal tissue and secrete IL-17
IL-17 stimulates resident renal cells to secrete chemokines and other inflammatory mediators, as well as recruits neutrophils
TH17 also secrete CCL20 (aka MIP-3), which signals recruitment of TH1 cells and monocytes
Resulting inflammation causes kidney damage
Which cell has an anti-inflammatory role in AKI?
Regulatory T cells
What is the barrier to transplantation?
Genetic incompatibility
What is the only form of treatment for most end-stage organ failure?
Transplantation
What are the two methods of preventing graft rejection?
HLA matching and immunosuppressants
What is chronic rejection?
Rejection of transplant months or years after procedure
What is acute rejection?
Rejection of transplant days to weeks after procedure
What is hyperacute rejection?
Immediate rejection of transplant
What are the targets of the antibodies responsible for rejection?
Histocompatability Ags
What is an autograft?
Grafts exhcanged from same individual
What is an Isograft?
Grafts exchanged between identical twins (same genetic constitution)
What is an Allograft?
Grafts exchanged between non-identical members of the same species
What is a Xenograft?
GRafts exchanged between members of different species (e.g. pig valve replacement)
What are the 5 steps in the immune response to the graft?
- Antigen Presenting Cells trigger CD4+ and CD8+ T cells
- Both local and systemic immune response develop
- Cytokines recruit and activate immune cells
- Development of specific T cells, NK cells, or Macrophages - mediated cytotoxicity
- Allograft rejection
What are the 4 variables that determine the outcome of the transplant?
Condition of the allograft
Donor-host antigen disparity
Strength of host anti-donor repsonse
Immunosuppressive regimen
When is ABO blood type not important?
Transplantation of Non Vascularized tissues
Corneal transplant
Heart valve
Bone and tendon
stem cell
Which blood type has no antibodies present?
AB
Which blood type has A and B antibodies?
O
Which blood type has both A and B antigens?
AB
Which blood type has no antigens?
O
Which grafts are do not need to consider anti-class I/II HLA antibodies?
Non vascularized tissues
Cornea
Heart Valve
Bone
