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Y5 Path > Immuno - autoimmune and autoinflamm disease > Flashcards

Immuno - autoimmune and autoinflamm disease Flashcards

1
Q

Graves disease - pathophysiology?

A

anti-TSH receptor antibodies –> activation of TSH receptor that is not responsive to -ve feedback

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2
Q

What type of hypersensitivity disorder is Graves disease

A

Type II

  • antibodies against self –> receptor activation
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3
Q

Which thyroiditis is associated with high T4? and which one with low T4?

A

High T4 = De Quervains (painful)

Low T4 = Hashimoto’s (anti-TPO)

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4
Q

Hashimoto’s thyroiditis - clinical Fx

A

Features of hypothyroidism (constipation, lethargy, cold intolerance)

GOITRE - irregular!

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5
Q

Why is there goitre in hashimoto’s thyroiditis?

A

Lymphocyte infiltration of the thyroid due to binding of autoantibodies

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6
Q

Which autoantibody is associated with Hashimoto’s

A

Anti-THRYOGLOBULIN

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7
Q

WHY is measuring anti-thyroid antibodies a bit shit

A

LOADS of women>65yo with antithyroid antibodies without any thyroid disease..only a small proportion actually have hypothyroidism

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8
Q

Low TSH. Normal T3/T4. What is the Dx and what is the significancd

A

Subclinical hyperthyroidism - may progress to primary hyperthyroidism, esp if they have anti-TPO +ve

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9
Q

Pathophysiology of T1DM? Therefore what type of hypersensitivity is it?

A

CD8+ T cells recognise auto antigens on beta cells

Type IV - t cell mediated

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10
Q

What auto antigens are recognised by T-cells in T1DM?

A

GAD65

IA2 (islet antigen 2)

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11
Q

Antibodies seen in T1DM

A

anti-islet cell
anti-GAD
anti-insulin
anti-IA2

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12
Q

Clinical Fx of B12 deficiency

A
  • Degeneration of cord
  • Optic neuropathy
  • Peripheral neuropathy
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13
Q

Pernicious anemia - what is it?

A
  • Autoantibodies to gastric parietal cells + intrinsic factor
    B12 malabsorption –> deficiency –> neurological Fx
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14
Q

Case: drooping eyelids + weakness on repetitive activity + Sx worse at end of day

Dx?

A

Myasthenia gravis

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15
Q

Myasthenia gravis = pathophysiology

A

Anti-AChR antibodies

Therefore ACh can’t bind and muscle cell is not depolarised –> no contraction

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16
Q

Special test for Dx of Myaesthenia gravis

A

Tension test

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17
Q

Myasthenia gravis - what type of hypersensitivity disorder is it?

A

Type II - antibody against a self antigen

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18
Q

Good pasture’s syndrome - what is the offending antibody?

A

Antibody vs alpha3 subunit of Type IV collagen

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19
Q

Immunohistochemistry for anti-GBM: what is a +Ve result?

A

linear IgG deposition along GBM

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20
Q

Best antibody for detecting rheumatoid arthritis

A

Anti-CCP

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21
Q

Name 2 genetic predispositions to rheumatoid arthritis?

A

1) HLA DR4 + 1 subtypes

2) PAD2 and 4 PMs

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22
Q

How does HLA affect susceptibility of RA?

A

Certain alleles of HLA DR4 and HLA DR1 bind to ARTHRITOGENIC PEPTIDES + CITRULLINATED PEPTIDES w high affinity

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23
Q

What infection is associated with rheumatoid arthritis? why?

A

P gingivalis - gum infection

It expresses PAD enzyme?! thus promotes citrullination

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24
Q

How does PAD polymorphism –> RA development?

A

PAD2 and 4 = involved in citrullination of arginine

Certain polymorphisms are associated with increased activity –> high load of citrullinated proteins

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25
What is rheumatoid factor
Antibody directed against Fc region of IgG. | This antibody is an IgM
26
B cell involvement in Rheumatoid arthritis - give 2 ways
1) Type 2 response = anti-CCP activity --> complement, NK and macrophage activation 2) Type 3 response = immune complexes formed (by Anti-CCP and RF) + deposited --> complement activation
27
How is the point affected (macroscopically) in RA
Increased synovial fluid volume Inflamed synovial tissue -> panes formation which invades cartilage + adj tissue
28
4 diseases assoc with ANA +ve
SLE Sjogren's Scleroderma Dermatomyositis
29
ANA +ve - is this result specific to autoimmune disease?
NO it is often found in normal individuals
30
Which cells are used to test for ANAs?
Hep2 cells
31
Pathogenesis of SLE
Antibodies against intracellular proteins IMMUNE COMPLEXES formed + deposited in tissues Complement activation + activation of cells expressing Fc receptors
32
How does staining pattern for IgG differs in good pasture's disease vs lupus nephritis?
Goodpastures = linear Lupus nephritis = lumpy bumpy, because there is immune complex deposition
33
What type of hypersensitivity reaction is SLE?
Type III = immune complex
34
You request an anti nuclear antibody test on two patients with joint pain Patient A’s result is 1:640 Patient B’s result is 1:80 Based on this information, which has the “strongest” (i.e most positive) antibody?
Patient A
35
Which autoantibody test is highly specific for SLE?
anti-dsDNA
36
anti-ENA vs anti-dsDNA antibodies Which one is useful in monitoring disease activity, and in which disease?
anti-dsDNA, in SLE
37
homogenous staining of the nucleus is associated with..?
anti-dsDNA
38
Speckled staining is associated with antibodies to...?
ENA? and Ro/La/Sm/U1RNP
39
Anti-Ro and Anti-La
Sjogren's syndrome
40
How does measuring complement levels help in monitoring disease in SLE?
can measure levels of UNACTIVATED C3 + C4 - LOW levels is associated with more active disease (they're being consumed because pathway is activated)
41
2 major antibody tests in anti-phospholipid syndrome?
1) Anti-cardiolipin | 2) lupus anti-coagulant
42
- Inflammation with Th17 and Th2 cells dominating - Cytokines --> activation of fibroblasts and fibrosis - Polymorphisms within type I collagen alpha 2 chains and fibrillin 1 may be important - Polymorphisms in TGF-b have also been described - Cytokines lead to activation of endothelial cells and contribute to microvascular disease - Loss of B cell tolerance to nuclear antigens
Systemic sclerosis
43
Systemic sclerosis - which cells predominate? Why is there telangiectasia + raynaud's? Why sclerodactyly?
Inflammation predom Th17 and Th2 cells Cytokine activation of endo- cells --> microvasc damage Cytokine activation of fibroblasts --> fibrosis
44
autoantibody in diffuse systemic sclerosis?
Anti-topoisomerase
45
autoantibody in limited systemic sclerosis?
Anti-centromere
46
Dermatomyositis + polymyositis - type of hypersensitivity ?
Dermatomyositis - Type III immune complex mediated vasculitis Polymyositis = Type Iv CD8 cells kill myofibres
47
Anti-Jo1
dermatomyositis
48
anti-snRP
polymyositis
49
3 types of small vessel vasculitis assoc with ANCA?
1) Granulomatosis with polyangiitis/Wegener's granulomatosis 2) Eosinophilic granulomatosis with polyangiitis/Churg-Strauss 3) microscopic polyangiitis
50
How do ANCAs lead to vasculitis?
In inflammation, antigens of primary granules in neutrophil cytoplasm get expressed on neutrophil CSM ANCAs recognise these leading to neutrophil activation --> endothelial damage
51
cANCA is associated with antibodies to what?
Proteinase 3
52
pANCA is associated with antibodies to what?
myeloperoxidase
53
cANCA and pANCA are associated with which diseases?
cANCA = wegener's/granulomatous polyangiitis pANCA = Churg strauss and MPA
54
Difference btw auto inflammatory and autoimmune diseases?
``` Autoinflamm = defect in innate immune response Autoimmune = defect in adaptive immune response ```
55
Name 2 diseases which are mixed auto inflammatory + autoimmune processes?
Ank spon | Psoriatic arthritis
56
Name 2 monogenic auto inflammatory diseases
Familial Mediterranean Fever | TRAPS - TNF Receptor Associated Periodic Syndrome
57
Clinical features of familial mediterranean fever?
Periodic fevers | + Peritonitis/Pleuritis/pericarditis/arthritis
58
MEFV gene encodes...?
Pyrin Marenostrin
59
2 step management of familial mediterranean fever?
Colchicine + Etanercept
60
2 cytokines which are often affected in monogenic auto inflammatory conditions?
IFNalpha + IL1
61
Mutation in AIRE protein - which disease si this?
APS aka APECED | Autoimmune polyendocrine syndrome
62
in APS (autoimmune polyendocrine syndrome), which 2 glands are affected? How does this manifest?
Parathyroids + adrenal | --> hypoPTH + addison's
63
Foxp3 mutation - which disease is this?
IPEX = immune dysregulation, polyendocrine, enteropathy, X-linked Foxp3 = T reg cells
64
what does IPEX stand for?
immune dysregulation, polyendocrinopathy, enteropathy, X-linked
65
any mutation in the FAS pathway - which disease is this?
ALPS = autoimmune lymphoproliferative syndrome
66
``` In ALPS (autoimmune lymphoproliferative syndrome), which cell type is at high levels? Findings on examination? ```
Lymphocytes are v v high Splenomegaly Large LNs assoc with lymphoma
67
Major mutation often seen in Crohn's disease
NOD2 mutation
68
NOD2 mutation - how does this lead to Crohns'?
Affects recognition of bacteria --> inappropriate response to bacteria --> crypt inflamm + granuloma formation + ulceration
69
Drugs used to treat Crohns' - name 4
Steroids Azathioprine MEsalazine Infliximab
70
Normal function of HLA B27?
Ag presentation to CD8+ t cells
71
Normal function of IL23 receptor?
differentiation of Th17 cells
72
In Ank Spon, which areas are vulnerable to enhanced inflammation?
insertion points of ligaments + tendons
73
HLA DR15 - which disease?
Anti-GBM
74
Name a polygenic auto inflammatory disease
Crohns'
75
3 aspects of peripheral tolerance
1) T-reg cells (CD24+Foxp3+) 2) Costimulation - T cells require recognition of antigen AND costimulatory molecule. If costimulatory molecule is absent --> T cell anergy 3) Immune privilege
76
3 parts of the body with immune privilege?
CNS Eyes Testes

Y5 Path (64 decks)

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