3.3 Immunology: Immune mediated renal disease Flashcards
Type I
Anti-Parasite immune response. IgE mast cells. Anaphalaxis. Test: IgE skin test
Type II
Normal Ab response. Antigen is not soluble. Neutrophils and macrophages. IgM and IgG
Type III
Normal Ab response. Antigen is soluble; Complement and FC receptor mediated recruitment Activates Leukocytes.
Immune complexes of circulating antigens and IgM or IgG antibodies deposited in vascular basement membrane
Type IV
Normal cell mediated response (T-Cell)
CD4 T cells: Delayed type hypersensitivity
CD8 CTLs: T cell mediated cytotoxicity
- Macrophage activation cytokine mediated inflammation
- Direct target cell killing cytokine mediated inflammation
Common causes of renal failure
DM, HTN, Immunologic
What type of Hypersensitivies are involved in immune mediated renal disease?
II,III,IV
What part of nephron is involved in immune mediated renal disease?
Glomerulus more than tubules
Nephrotic syndrome vs. Nephritic Syndrome
Nephrotic syndrome: Increased permeability of GBM due to cytokine release: Proteinuria
Nephritic syndrome: Inflammation of glomerulus and neutrophil activation: Hematuris
Innate host defenses
Inflammation; neutrophils attracted
Adaptive immune response
activated LN draining kidney
Pro-inflammatory cytokines
IL-1, IL-6,TNF
Hot t-BONE stEAK
Important interleukin cytokines:
IL-1: fever (hot)
IL-2: T cell stimulator
IL-3: Bone marrow stimulator (sim to GM-CSF)
IL-4: IgE (class switching from IgG), B cell growth
IL-5: IgA, eosinophils
IL-6 aKute renal failure
GM makes classic cars
IgG and IgM activate the classic complement pathway (Ag:Ab complexes –> C1…)
How does activation of immunologic cells occur?
Injury to renal tissues–>Necrosis–>PRR+DAMP–>Activation of PRR expressing renal cell
What are immune complexes?
Ab+ antigens=immune complex
Mechanism for removal of antigens for body
What is the most common mechanisms of immune injury in renal disease?
Immune complexes
Preformed immune complexes?
Ab to circulating antigens
collect between vasc endothelium and glomerular BM
In situ immune complexes
Ab to antigens trapped to epithelial of glomerular space bind to these antigens
MEchanism of IC
Deposit on vessel, kidney glomeruli–>Activate complement–>Recruitment of phagocytes–>Inflamm response–>Enzymes release from neutrophils damage
IC disease (4)
Serum sickness nephritis, Post infectious glomerulonephritis, IgA nephropathy (Henoch-schonlein purpura), Lupus nephritis (SLE)
C3a, C5a
Anaphylaxis, activation of complement
ACID
Types of hypersensitivity:
Type I: Anaphylactic and Atopic
Type II: Cytotoxic (antibody-mediated)
Type III: Immune complex
Type IV: Delayed (cell mediated) T cell
Post infectious glomerulonephritis. Associated ab?
10-14 days post strep throat
ab to ASO, DNAase B, Hyaluronidase
Urine dysmorphi red blood cells, RBC casts; little protein
IF of post infectious glomerulonephritis with granular appearance
granular, lumpy humpy, antibody IgG is not directed against a component of kidney
IgA nephropathy
Characterized by glomerular IgA deposits; Antigen not known- often follows pharnygitis
Complement by alt pathway
Systemic Lupus Erythematous
Autoimmune, chronic inflamm disorder, immune complex mediated, nuclear antigens (ANA; anti-dsDNA)
Lupus Nephritis
Granular Ig deposits
Ab reacts with kidney antigen
Ag-Ab complexes aggregated with C3, C4, C1q
Antibody mediated disease: Anti-GBM disease (good pasture) Characteristic
Glomerulonephritis+ pulmonary hemorrhage
Goodpasture IF
Linear staining of BM
Antigen of goodpasture
Type IV collagen
Triggers for goodpasture
Genetics, exposure to hydrocarbons or influenza infection
ANCA associated Nephropathies
Small vessel vasculitidies: Anti-neutrophil cytoplasmic antibodies
Churg-Strauss syndrome (p-ANCA- perinuclear) Wegeners granulomatosus (c-ANCA- cytoplasmic) Microscopic polyangitis (p-ANCA)
Mechanism of ANCA
ab to PR3 or to MPO activate neutrophils to relase reactive oxygen species, lysosomal enzymes and chemokines which initiate an inflammatory response and damage endothelial cells
Myeloma Kidney
Monoclonal immunoglobulin deposition disease.
Uncontrolled prolif of a single clone of B cells resulting in synthesis and secretion of monoclonal Ig or Ig fragments.
Bence Jones Proteins
Monoclonal light chains
Myeloma kidney lesions
Interstitial protein casts located in distal nephron and collecting tubules.
Casts are surrounded by macrophages
Casts block system leading to tubular atrophy, interstitial fibrosis and calcification
Casts consist of B-J proteins coaggregated with Tamm Horsfall proteins (uromodulin) produced by cells in loop of henle
T cell mediated disease
Minimal change nephrotic syndrome.
Tubulointerstitial nephritis
Minimal change nephrotic syndrome
No immunoglobulin or complement seen on IF.
Common in kids
Respond to steroids and cyclophosamide
Tubulointerstitial Nephritis
inflammatory change due to infection or drugs
Oliguria and acute renal impairment
Interstitial tissue infiltrated granulocytes, mononuclear cells and eosinophils
Granuloma formation suggests T cell mediated etiologies–>Type IV
Presence of IgE and eosinophilia hints at Type I Hypersens
Circulating immune complexes
3 diseases
Serum sickness
Postinfect GN
Lupus nephritis
Insitu immune complex formation 3 disease
Membranous GN
IgA nephropathy
Henoch Schonlein nephritis
Ab mediated
goodpasture syndrome
Anti-neutrophil cytoplasmic antibody
Wegener granulomatosis, microscopic poly angitis, churg strauss vasculitis
T-Lymphocyte mediated
Tubulointerstial nephritis
Type IV collagen
Good pasture
Tubular BM protein
Interstitial nephritis
Tumor antigens
Membranous nephropathy
Thyroid antigens
Membranous nephropathy
Autologous antigens
Lupus nephritis
Foreign Serum
Serum sickness
Food antigens
IgA nephropathy