Microbiology Flashcards
ANCA + asthma+ eosinophils
Churg-Strauss syndrome
cANCA+ respiratory necrotizing granulomatosis
Wegener’s granulomatosis
Anti-GBM autoantibodies+ lung hemorrhage
Goodpastures syndrome
To cause kidney immune disease an antigen must trigger this
a local immune inflammatory response
Nonrenal antigens mechanism for depositing in the kidney
usually bloodborne and attach to a specific antibody, forming immune complexes that circulate to the kidney
Berger disease
- Focal glomerulonephritis
- Presents with hematuria
- Follows acute upper respiratory infection in young males
- IgA deposits in the glomerular mesangium
Where do bacterial antigens complexed with IgG tend to localize?
within the GBM
or
on the epithelial side of the GBM because of their smaller sizes
An example of a systemic disease associated with Berger’s disease
Henoch-Schonlein purpura (HSP)
Where is the glomerular capillary bed situated?
Between two arterioles NOT between an arteriole and a venule as in other capillary beds
What is the high glomerular capillary pressure due to?
Resistance afforded by the efferent arterioles
Why is capillary pressure always greater than the pressure in Bowman space?
Only filtration occurs
Describe fluid flow through the glomerular capillary membrane
unidirectional with no associated reabsorption by the capillaries
Ag-Ab complexes establish immune inflammatory renal injury via:
- Type I-IV hypersensitivities
- direct complement activation
- immunodeficiency disorders (AIDS)
IgE-mediated (type 1 hypersensitivity) immune response is triggered when..
- Allergen sensitive T cells contact specific allergens
- releasing pro-allergic interleukins IL-4 and IL-5
- which enhance production of IgE by class switching and
- activate mast cells and basophils
IgE coating of basophils and mast cells in the presence of allergen causes the release of…
- vasoactive amines (histamine causing vasospasm)
- chemokines (RANTES)
- prostaglandin synthesis
- platelet mediated coagulation, thrombosis and fibrin deposition
When allergen sensitive T cells contact specific allergens in Type I hypersensitivity this causes the release of
IL-4 and IL-5
IL-4 and IL-5 enhance the production of what?
IgE by class switching
Allergic tubulointerstitial renal disease due to penicillins is associated with…
- penicillin or its metabolic products act as HAPTENS
- IgE deposition on mast cells-activation
- eosinophilia
- eosinophilic infiltration in the kidney
- responsiveness to corticosteroids
- rapid improvement after discontinuation of the causative drug
What type of hypersensitivity is Goodpastures disease?
Ab mediated (type II) renal disease
What is renal damage caused by in Type II (Goodpastures) renal disease?
linear deposition of anti-collagen IV antibody
C5a
anaphylactic and chemotactic
Type II renal damage steps
- Ag-Ab complex activates complement-MAC
- Tissue injury: creating membrane channels (MAC) and attracting other inflammatory cells to participate in the immune response (C5a fragment attracts neutrophils)
What do C5a fragments attract
neutrophils
A specific antigen component of the neutrophil cytoplasm that ANCA recognizes
Myeloperoxidase (MPO)
Most common category of the rapidly progressive glomerulonephritides
Pauci-immune (type III) crescentic glomerulonephritis
Why is it termed Pauci-immune?
Because there is no detectable IgG or C3 immunofluorescence within the glomerular basement membrane
3 conditions associated with ANCA auto Abs:
- ) type III idiopathic crescentic glomerulonephritis
- ) Wegener granulomatosis
- ) microscopic polyangiitis
Wegener granulomatosis
c-ANCA
ANCA + cytoplasmic antigens activate:
neutrophils
Neutrophil beta2 integrins action
Wegener granulomatosis
attraction and rolling of neutrophils along vascular endothelium of the kidney (ADHESION)
What two endothelial surface interaction ligands are upregulated in Wegener granulomatosis?
ICAM-1 and ELAM-1
Histopathology of clinical Wegener features
- necrotizing rapidly progressive crescentic glomerulonephritis
- T-cell mediated granulomas in the kidney and respiratory tract
Renal biopsy pattern in immune complex-mediated (type III hypersensitivity)
Antibody and complement in these location in a lumby-bumpy pattern
Granular “lumpy-bumpy” pattern are deposits of…
- IgG along the GBM of peripheral capillary loops
- components of the classical pathway of complement
Factors affecting localization of immune complex
- ) Release of vasoactive substances that enhance vascular permeability
- ) Presence of receptors:
- CR1 receptor of C3b on glomerular epithelial cells
- FcR for Fc fragment of IgG on mesangial and interstitial cells
Renal transplant acute rejection is mediated by
T cells (type IV) that are directed against MHC-1
During acute renal transplant rejection the release of this induces IL-2 syntesis
IL-1
TH cells stimulate these cells in the presence of IL-2 during acute rejection
Tc cells
What do activated Tc attack during acute rejection?
Foreign antigens of the graft resulting in cell-mediated immune inflammation
During acute rejection alloreactive antibodies contribute to this
vascular injury
During chronic rejection alloAgs T cells produce these that induce endothelial and intimal smooth muscle cell proliferation
cytokines
The production of cytokines during chronic rejection lead to…
luminal occlusion and graft arteriosclerosis
Poststreptococcal glomerulonephritis (PSGN) pathogenesis
- T cells stimulate by streptococcal wall Ags may cross react with renal glomerular Ags resulting in:
- progressive cell death
- sclerosis of the renal parenchyma
Hyperacute refection in presensitized host, preformed antibodies react with…
alloantigens on the vascular endothelium of the transplanted kidney
Hyperacute rejection results in…
acute renal ischemia, infarction, and transplant loss
Where does C3b local immune inflammatory injury occur when C3b deposit?
- In the phagocytic mesangium of the glomerulus
- subendothelially
- along C3b binding sites within the capillary wall
C3b
opsonin
Half of C3 deposition renal disease patients have this
C3 convertase
Type I of Membranoproliferative glomerulonephritis features distinguished on renal biopsy
Immune complex deposit C3 deposited primarily on subendithelial sites along capillary wall
Type II of Membranoproliferative glomerulonephritis features distinguished on renal biopsy
associated primarily with dense intramembranous deposits of C3 nephritic factor
Type III of Membranoproliferative glomerulonephritis features distinguished on renal biopsy
Mixture between types I and II
Pathway activated in MPGN Type I
classic pathway
Interposition of mesangial cell cytoplasm between the GBM and endothelial cell + glomerulosclerosis leads to…
renal failure
Pathway activated in MPGN Type II
alternative pathway
GBM appearance in MPGN Type I
double contours, rail track appearance
Basement membrane appearance in MPGN Type II
Appears thick and looks like a ribbon
RBC contain C3b/C4b receptor and regulate what?
C3bBb
How do RBCs that contain C3b/C4b receptor regulate C3bBb?
By binding C3b in immune complex, making it available for cleavage and inactivation by serum factor I
Male, urban, black IV drug users
- proteinuria
- rapidly pregressive HIV-associated FSGS
White homosexual seropositive patients
- Nonproteinuric
- more slowly progressive HIV nephropathy
HIV FSGS is characterized early by…
Focal deposition of IgM and C3 which leads to scarring of the glomeruli
** kidneys can fail
Immune complex type renal involvement in patients with HIV probably results from what?
circulation of bacterial, viral, or tumor associated immune complexes to the kidney
HLA-B12 (MCH I)
PSGN
HLA-B35 (MHC I) and HLA-DR4 (MHC II)
IgA neuropathy
HLA-DR2 (MHC II)
Anti-GBM or Goodpastures syndrome
Prevalence of asymptomatic bacteriuria in pregnant women
4-7%