15. Immunological Aspects of the Renal System Flashcards
How can DAMPs lead to renal inflammation?
They are released from dying parenchymal cells. C-reactive protein can then bind and activate complement pathway. Immune cells can also recognize DAMPs via Toll-like receptors and induce immune response and renal inflammation.
Which immune cells is produces the most pro-inflammatory cytokines and is involved in most kidney diseases?
Macrophages
What do DCs differentiate into in the early stage of AKI?
Th17 and Th1
Th17 is dominate in the early stage
Th1 is dominate in the late stage
What kind of macrophage cells play a key role in AKI? What kind plays a key role in repair?
AKI: M1 MΦ (classically activated)
Repair: M2 MΦ (alternatively activated
What is Th17 cells’ role in AKI?
They secrete IL-17 which stimulates resident renal cells to secrete cytokines and chemokines. It also leads to the expression of CCL20 which leads to the recruitment of neutrophils, monocytes, Th1, and more Th17 cells.
Why is the kidney uniquely susceptible to complement induced damage?
Filtration favors tissue deposition of immune complexes. This leads to the activation of the classical, alternative, and lectin complement pathways. Further activation of membrane attack complexes (MAC) trigger massive cell death.
Which complement proteins directly stimulate proinflammatory responses in neutraphils and MΦ cells?
C3a and C5a
What is the difference between a Type II and Type III hypersensitivity?
Type II: IgG or IgM binds to cell-bound antigen. Leads to cell lysis.
Type III: IgG and IgM bind to soluble antigen. Leads to tissue damage where it is deposited.
What are the three different types of host vs graft rejections?
Hyperacute (type II): immediate and caused by antibodies.
Acute (type IV): days to weeks after transplant, caused by T cells.
Chronic (type IV): months to years after transplant, caused by vascular trauma, inflammatory products and macrophages.
Define an autograft, isograft, allograft, and xenograft.
Autograft: from same individual
Isograft: from genetically identical individuals (identical twins)
Allograft: from same species
Xenograft: from different species
How does one test of pre-existing non-ABO antibodies?
Microcytotoxicity Test for Preformed Abs
Recipient serum with abs is added to donor cells. Complement and dye is added. If dye accumulates in cells, preformed Abs are present.
How does one test for class I HLA compatibility?
Microcytotoxicity Test for Class I HLA
Donor cells and recipient cells are extracted separately. Abs to specific HLA antigen and complement are added. Then dye is added. If dye is in both cells, then HLA are identical.
How does one test for class II HLA compatibility?
Mixed Lymphocyte Response (MLR)
Donor cells given radiation dose to prevent proliferation, but allows them to still serve as APCs. Mix with recipient cells. Radioactive thymidine is added, which is incorporated into DNA if there is proliferation. If proliferation, classes to not match and vice versa.
What is the difference between direct and indirect allorecognition?
Direct: T cell recognizes unprocessed allogeneic MHC molecule on graft APCs.
Indirect: T cell recognizes processed peptide of allogeneic MHC molecule on host APC
What are the two main effector mechanisms for host vs graft rejection? What cells and cytokines to they use?
Humoral: Th2 (IL-4, IL-5, and IL-10)
Cellular: Th1 (IL-2, IFN-γ)
