3.3 Immunology: Immune mediated renal disease

Question 1

Type I

Answer 1

Anti-Parasite immune response. IgE mast cells. Anaphalaxis. Test: IgE skin test

Question 2

Type II

Answer 2

Normal Ab response. Antigen is not soluble. Neutrophils and macrophages. IgM and IgG

Question 3

Type III

Answer 3

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

Question 4

Type IV

Answer 4

Normal cell mediated response (T-Cell)

CD4 T cells: Delayed type hypersensitivity

CD8 CTLs: T cell mediated cytotoxicity

1. Macrophage activation cytokine mediated inflammation
2. Direct target cell killing cytokine mediated inflammation

Question 5

Common causes of renal failure

Answer 5

DM, HTN, Immunologic

Question 6

What type of Hypersensitivies are involved in immune mediated renal disease?

Answer 6

II,III,IV

Question 7

What part of nephron is involved in immune mediated renal disease?

Answer 7

Glomerulus more than tubules

Question 8

Nephrotic syndrome vs. Nephritic Syndrome

Answer 8

Nephrotic syndrome: Increased permeability of GBM due to cytokine release: Proteinuria

Nephritic syndrome: Inflammation of glomerulus and neutrophil activation: Hematuris

Question 9

Innate host defenses

Answer 9

Inflammation; neutrophils attracted

Question 10

Adaptive immune response

Answer 10

activated LN draining kidney

Question 11

Pro-inflammatory cytokines

Answer 11

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

Question 12

GM makes classic cars

Answer 12

IgG and IgM activate the classic complement pathway (Ag:Ab complexes –> C1…)

Question 13

How does activation of immunologic cells occur?

Answer 13

Injury to renal tissues–>Necrosis–>PRR+DAMP–>Activation of PRR expressing renal cell

Question 14

What are immune complexes?

Answer 14

Ab+ antigens=immune complex

Mechanism for removal of antigens for body

Question 15

What is the most common mechanisms of immune injury in renal disease?

Answer 15

Immune complexes

Question 16

Preformed immune complexes?

Answer 16

Ab to circulating antigens

collect between vasc endothelium and glomerular BM

Question 17

In situ immune complexes

Answer 17

Ab to antigens trapped to epithelial of glomerular space bind to these antigens

Question 18

MEchanism of IC

Answer 18

Deposit on vessel, kidney glomeruli–>Activate complement–>Recruitment of phagocytes–>Inflamm response–>Enzymes release from neutrophils damage

Question 19

IC disease (4)

Answer 19

Serum sickness nephritis, Post infectious glomerulonephritis, IgA nephropathy (Henoch-schonlein purpura), Lupus nephritis (SLE)

Question 20

C3a, C5a

Answer 20

Anaphylaxis, activation of complement

Question 21

ACID

Answer 21

Types of hypersensitivity:

Type I: Anaphylactic and Atopic
Type II: Cytotoxic (antibody-mediated)
Type III: Immune complex
Type IV: Delayed (cell mediated) T cell

Question 22

Post infectious glomerulonephritis. Associated ab?

Answer 22

10-14 days post strep throat
ab to ASO, DNAase B, Hyaluronidase

Urine dysmorphi red blood cells, RBC casts; little protein

Question 23

IF of post infectious glomerulonephritis with granular appearance

Answer 23

granular, lumpy humpy, antibody IgG is not directed against a component of kidney

Question 24

IgA nephropathy

Answer 24

Characterized by glomerular IgA deposits; Antigen not known- often follows pharnygitis

Complement by alt pathway

Question 25

Systemic Lupus Erythematous

Answer 25

Autoimmune, chronic inflamm disorder, immune complex mediated, nuclear antigens (ANA; anti-dsDNA)

Question 26

Lupus Nephritis

Answer 26

Granular Ig deposits Ab reacts with kidney antigen Ag-Ab complexes aggregated with C3, C4, C1q

Question 27

Antibody mediated disease: Anti-GBM disease (good pasture) Characteristic

Answer 27

Glomerulonephritis+ pulmonary hemorrhage

Question 28

Goodpasture IF

Answer 28

Linear staining of BM

Question 29

Antigen of goodpasture

Answer 29

Type IV collagen

Question 30

Triggers for goodpasture

Answer 30

Genetics, exposure to hydrocarbons or influenza infection

Question 31

ANCA associated Nephropathies

Answer 31

Small vessel vasculitidies: Anti-neutrophil cytoplasmic antibodies ``` Churg-Strauss syndrome (p-ANCA- perinuclear) Wegeners granulomatosus (c-ANCA- cytoplasmic) Microscopic polyangitis (p-ANCA) ```

Question 32

Mechanism of ANCA

Answer 32

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

Question 33

Myeloma Kidney

Answer 33

Monoclonal immunoglobulin deposition disease. | Uncontrolled prolif of a single clone of B cells resulting in synthesis and secretion of monoclonal Ig or Ig fragments.

Question 34

Bence Jones Proteins

Answer 34

Monoclonal light chains

Question 35

Myeloma kidney lesions

Answer 35

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

Question 36

T cell mediated disease

Answer 36

Minimal change nephrotic syndrome. Tubulointerstitial nephritis

Question 37

Minimal change nephrotic syndrome

Answer 37

No immunoglobulin or complement seen on IF. Common in kids Respond to steroids and cyclophosamide

Question 38

Tubulointerstitial Nephritis

Answer 38

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

Question 39

Circulating immune complexes | 3 diseases

Answer 39

Serum sickness Postinfect GN Lupus nephritis

Question 40

Insitu immune complex formation 3 disease

Answer 40

Membranous GN IgA nephropathy Henoch Schonlein nephritis

Question 41

Ab mediated

Answer 41

goodpasture syndrome

Question 42

Anti-neutrophil cytoplasmic antibody

Answer 42

Wegener granulomatosis, microscopic poly angitis, churg strauss vasculitis

Question 43

T-Lymphocyte mediated

Answer 43

Tubulointerstial nephritis

Question 44

Type IV collagen

Answer 44

Good pasture

Question 45

Tubular BM protein

Answer 45

Interstitial nephritis

Question 46

Tumor antigens

Answer 46

Membranous nephropathy

Question 47

Thyroid antigens

Answer 47

Membranous nephropathy

Question 48

Autologous antigens

Answer 48

Lupus nephritis

Question 49

Foreign Serum

Answer 49

Serum sickness

Question 50

Food antigens

Answer 50

IgA nephropathy