Renal Immunology Flashcards
What are the two ‘categories’ of antigen that are responsible for Renal Immune disease ?
Renal Self: GBM Collagen IV, Foreign: HLA from Transplants Non-Renal Self: Nucleic acids, Tumor antigen, Cryoglobulin Non-Self: Infectious, allergens,Drugs
In order for antigen to create an immune Rxn in the kidney it must either be endogenous in the kidney or be deposited (non-renal). What do most non-renal antigens form in order to be deposited in the Kidney ?
Immune complexes (Type III) floating in the blood
Where are the 4 sites that immune complexes will deposit in the kidney ?
Glomerular mesangium
Glomerular Basement Membrane (GBM)
Endothelial cells lining the inside of the GBM
Endothelial cells lining the outside of the GBM
In Berger Disease (IgA nephropathy) where will IgA deposit ? Why ?
In the mesangium
IgA is a large molecule and will not penetrate to the GBM
Where will bacterial antigens complexed with IgG tend to localize ?
WIthing the GBM or on the epithelial side of the GBM.
Is Berger Disease diffuse or focal ?
Focal (only occurs in a small portion
Berger disease usually presents with which renal complication ?
Hematuria
Berger disease usually follows what occurrence in young males ?
Upper respiratory infection
What systemic disease is associated with Berger Disease ?
Henoch-Schonlein Purpura
What is unusual about glomerular capillary beds ?
It is situated between two arterioles instead of an arteriole and a venule
Normally, Capillary pressure should always be higher than Bowman space thus leading to ….
filtration
What type of Ig mediates Type I hypersensitivity ?
IgE
What type of Ig mediates type II hypersensitivity ?
IgM, IgG (Direct binding)
What type of Ig mediates Type III hypersensitivity ?
IgM, IgG ( Immune Complex)
What mediates Type IV hypersensitivity ?
T-Cells
Besides the hypersensitivity run’s, Ag-Ab complexes initiate immune inflammatory injury via which two mechanisms ?
Direct Compliment activation
Immunodeficiency disorders
AIDS, etc
Anti-GBM disease, Anti-TBM, hyper acute rejection and Wegner Granulomatis are all associated with which kind of hypersensitivity ?
Type II (Direct Cytotoxic )
Leads to linear deposition (smooth, not lumpy bumpy)
Anti GBM disease is due to Ab’s directed at which antigen ?
GBM (Type II)
Anti-TBM disease is due to Ab’s directed at which antigen ?
Tubular membrane antigens (Type II)
Hyper-acute rejection syndrome is due to Ab’s directed at which antigen ?
Class I -HLA (Type II)
Wegner Disease is due to Ab’s directed at which antigen ?
Cytoplasmic MPO of neutrophils
What is the distinction given to Immune complex associated Glomerulonephritis (GN) on immunofluorescence ?
Lumpy-Bumpy deposition ( Type III)
Chronic Renal Allograft rejection is due to cell mediated hypersensitivity (Type IV). What antigen is this immune response directed at ?
Class II HLA antigens
What pattern of damage do you see in Cell mediated hypersensitivity in the kidney ?
Diffuse, granular
What kind of immune reactions is responsible for Chronic GN ?
Type IV (cell mediated) directed at renal antigens
Immmune tubular interstitial disease is mediated by which kind of immune run ?
Type I (IgE mediated)
Membranoproliferative GN is due to which kind of immune rxn ?
Direct C mediated (Alternative pathway). Immune compled to C3 nephritic factor.
In AIDS you will see focal segmental GN due to which antigen ?
HIV !
Lupus- Like Syndrome is due to deficiency in what immune product ?
Complement
Hemolytic uremic syndrome is due to deficiency in which factor ?
Factor H deficiency.
When allergen sensitive T-Cells encounter specific antigen, they release which two interleukens that lead to increased IgE production ?
IL-4 and 5
IgE that is created during a Type I hypersensitivity will attach to Mast and Basophils, activating them. When these Mast Cell/IgE complex come into contact with antigen which vasoactive amine(s) are released ?
Histamine…..
Chemokines are also released: MCP-1, RANTES, IP-10
Prostaglandins are produced
Allergic Tuberointerstitial disease is often caused by sensitivity to which anti-biotic ? What kind of hypersensitivity is this ?
Penicillin
Type I
What factor is released during Allergic Tuberointerstial disease that leads to eosinophilia ?
ECF (Eosinophil chemotactic pattern)
What class of drugs has a good response when used to treat Allergic Tuberointerstitial disease ?
Corticosteroids
Goodpastures disease is a Type II disease which shows linear deposition of which antibody on which self antigen ?
Collagen IV (Anti-Collagen IV anti-body)
What is the cause of cell damage in Goodpasture Disease ?
Antigen-Anti-body complex activating complement leading to the formation of MAC.
MAC directly damages cells
Complement particles are chemotactic for other inflammatory cells (C5a –> Neutrophils)
Neutrophils lead to the release of lysozyme causing major oxidative damage.
Anti-Nuclear Cytoplasic Anti-bodies are specific for cytoplasmic constituents in which cells ?
Neutrophils
What do ANCA’s target ?
MYELOPEROXIDASE lysozyme elastase proteinase 3 (c-ANCA antigen.) lactoferrin cathepsins B, D, and G
What does it means to be “Pauci-immune” ?
No demonstration of immune components on immunofluorescence, however ANCA still plays a role
You will not see IgG or C3 in the basement membrane of the glomerulus
What are the three diseases that must be differentiated why referring to Pauci-Immune Rapidly progressing glomerulonephritides ?
Type III Idiopathic Crescentic glomerulonephritis
Wegner Granulomatosis
Microscopic Polyangiitis
Which of the Pauci Immune diseases is most common of the Rapidly Progressing glomerulonephritides ?
Type III Idiopathic Crescentic Glomerulo Nephritis
Wegners Granulomatosis is the prototype ANCA related renal disease. What is the most predominant form of ANCA in this disease ?
cANCA (90%)
The binding of ANCA to cytoplasmic targets in neutrophils leads to the up-regulation of which molecules on neutrophils ?
Beta 2 integrin : rolling adhesion
ICAM-1 : Tight Binding
ELAM 1 : Adhesion
Overall this activation leads to increased extraversion into areas of the body, in this case the glomeruli
Describe the Histopathology of Wegners ?
Rapidly progressing crescentic GN
T-CEll Mediated Granulomas in the Kidney and Respirtory tract
how can you tell the difference between WG and Microscopic polyangiitis ?
There will be vasculitis without the formation of granulomas or deposition of Ig i
What is the difference between WG and Idiopathic Crescentic GN ?
Idiopathic Crescentic GN does not include the Lungs whereas WG will include lung lesions
Where will immune complexes (Type III) typically aggregate ?
Mesangium
Glomerular Capillary Wall
Renal interstitium.
In Type III hypersensitivity, what pattern will be shown in immunofluroscopy of Ab-Complement ?
“Lumpy Bumpy” not linear deposition seen in Type II.
What are the two ways in which immune complex come to be in the kidney ?
- Antigen is planted in the kidney, circulating Ab binds to it as it passes through
- Ag-Ab complex is in the blood flow and settles out –> Deposition in mesangium and glomerular capillary wall
What kind Complement pathway is often associated with Type III hypersensitivity ?
Classical (needs Ab-Ag complex to be activated)
What will the effect of vasoactive substances have on the deposition of immune complexes ?
It will allow for increased penetrance of immune complexes since it makes the endothelium more permeable.
The CR1 receptor on glomerular epithelial cells is specific for which complement fragment ?
C3b
The Fc receptor for the Fc portion of IgG is found on which cells in the glomerulus ?
Mesangial
Interstitial Cells
In acute organ rejection of the kidney, MHC1 is processed monocytes and macrophages. These cells will then release IL-1 which leads to IL-2 synthesis. What important function does IL-2 have in Acute Organ Rejection ?
Activates T-Helper cells which in turn activate T-cytoxic (CD8) cells which attack the foreign organ Acute Rejection sounds like a Type IV (cell mediated) hypersensitivity ?
Wasn’t sure since in the chart is had said MHCI recognition was hyper-acute and thus type II
In Chronic Organ rejection, the activated T-cells produce cytokines. How do these cytokines affect organ transplant success ?
Cytokines induce the proliferation of endothelial and smooth muscle cells. This leads to occlusion of renal blood vessel –> destruction of organ tissue due to arteriosclerosis
Delayed Type Hypersensitivity to alloantigens in graft vessels.
What occurs in Post-Streptococcal Glomerulonephritis that leads to organ damage/failure ?
T-Cells stimulated by Streptococcal wall Ag’s may cross react with glomerular Ag’s leading to sclerosis of parenchyma and progressive death
In hyperacute rejection, a presensitized host has preformed Ab’s to to allograft endothelium. Activation of what immune component leads to intravascular thrombosis and sclerosis leading to acute ischemia or infarction of the transplant ?
Complement system
Are Ab’s involved in direct Complement mediated renal disease ?
NOPE !
This is done by the alternative pathway involving (C3 and properidin)
In the alternative pathway, properidin stabilizes which molecule to allow for activation ?
C3bBb (C3 convertase)
C3bBbC3b is also known as ?
C5 convertase
Direct complement activations results in which disease ?
Membranoproliferative Glomerulonephritis (MPGN)
What is MPGN characterized by ?
proliferation of cellular elements within the renal corpuscle and increased capillary wall thickness.
Type I MPGN is associated with what deposited in the sub endothelial sites along the capillary wall.
C3 (IgM/G)
Type II MPGN is associated with
Dense intramembranous deposits of C3 Nephrotic Factor
There is a third one which is a mixture of the first to Membrano Proliferaive Glomerulonephritis.
What complement pathway does Type I MPGN activate ?
Classical (C3 and IgM/G)
What Complement pathways does Type II MPGN activate ?
ALternative
How does the appearance of the basement membrane in Type I/II MPGN differentiated ?
Both Cause thickening, however in Type I you will see : Tram Tracking
In Type II: Ribboning (Due to C3 Nephrotic Factor)
Whats is C3 Nephrotic Factor ?
IgG auto-antibody to the Alternative Pathway C3b Convertase
Causes Stabilization of C3 Covertase
Acts like Properidin
Protects it from degradation by Factor I
HIV is associated with Focal Segmental Glomerulosclerosis (FSGS). Which ethnic group is associated with rapidly progressing FSGS
African Americans
IV drug users
Often present with PROTEINURIA
(Whites usually have less quickly progressing, also have no proteinuria seen)
Early FSGS is characterized by ….
Focal deposition of IgM and C3 –> Scarring of the glomeruli
–> Blood filtration and urine production impaired
Later Histopathology of FSGS shows which kind of cells on Renal biopsy ?
Many CD8 and CD2+ T-Cell infiltrates and more extensive collapse of entire glomeruli.
What structures seen in the glomerular endothelial wall suggest a viral role in late stage FSGS ?
Tubuloreticular strutures.
Immune Complex- like disease in patients with HIV typically arise from
circulation of bacterial, viral, or tumor-associated immune complexes to the kidney, triggering an immune complex-mediated renal disease
IgA Glomerulonephritis is seen with which Histocompatability complexes ?
HLA-B35 (MHC I) and HLA-DR4 (MHC II)
Anti-GBM or Goodpasture syndrome are seen with which Histocompatability complex ?
HLA-DR2 (MHCII)
