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Path Immunology > Hypersensitivity Disorders > Flashcards

Hypersensitivity Disorders Flashcards

1
Q

Type 1 HD - what is it? mediated by?

A

Immediate reaction provoked by re-exposure to an allergen.

IgE mediated - Mast cells release mediators resulting in vasodilation, increased permeability, smooth muscle spasm

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2
Q

Type 1 HD - Typical Symptoms?

A

Angioedema, urticaria, rhinoconjunctivitis, wheeze, diarrhoea and vomiting, Anaphylaxis

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3
Q

prevalence of allergic disorders in UK in children 13-14 years old

A

Asthma - 30% (4% also had concurrent clinical food allergy)
Allergic rhinitis - 20%
Atopic dermatitis - 15%
Food allergy - 2.3%

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4
Q

What is the atopic triad?

A

eczema, asthma and hay fever.

Possibly due to hygiene hypothesis

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5
Q 
T1HD - Atopic Dermatitis (infantile eczema) 
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Irritants, food and environmental
Pathology - Defects in beta defensin predispose to Staph aureus superinfection.
Diagnosis - clinical. 80% present in first year of life
Treatment - Emollients, skin oils, topical steroids, antibiotics, PUVA phototheraphy

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6
Q 
T1HD - Food Allergy
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Milk, eggs, peanuts, tree nuts, fish, shellfish
Pathology - IgE (anaphylaxis, OAS); cell mediated (coeliac); IgE/cell mediated (atopic dermatitis)
Diagnosis - Food Diary, skin prick test, RAST, Challenge test. Most resolved by adulthood
Treatment - Dietician, Food avoidance, Epipen, Control asthma if present

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7
Q 
T1HD - Oral Allergy Syndrome OAS
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Birch pollen + rosacae fruit, ragweed + melons, mugwort + celery (cross reactivity)
Pathology - exposure to allergen induces allergy to food. Symptoms limited to mouth 2% get anaphylaxis
Diagnosis - Clinically, skin prick testing can be useful
Treatment - Avoid food. If ingested was mouth, take anti-histamine

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8
Q 
T1HD - Latex food syndrome
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Chestnut, avocado, banana, patato, tomato, kiwi, papaya, eggplant, mango, wheat, melon
Pathology - Some foods have latex like components and hence latex allergy sufferers will also have food allergies
Diagnosis - Skin Prick Test
Treatment - Strict avoidance of causative food

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9
Q 
T1HD - Allergic Rhinitis
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Seasonal (tree and grass pollen, fungal spores), Perennial (pets, house dust mites); Occupational (latex, lab animals)
Pathology - Nasal itch and obstruction, sneezing, anosmia, eye symptoms
Diagnosis - Pale bluish swollen nasal mucosa; Skin Prick Test and RAST
Treatment - Allergen avoidance, Anti-Histamine, Steroid Nasal spray, Sodium Cromoglycate Eye Drops, Oral Steroids, Ipratropium Nasal Spray, Grass pollen desensitisation

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10
Q 
T1HD - Acute Urticaria
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - 50% idiopathic, 50% caused by food, drugs, latex, viral infections and febrile illnesses
Pathology - IgE medicated reaction. Wheals which completely resolve within six weeks
Diagnosis - Mainly clinical (sometimes skin prick test)
Treatment - Allergen avoidance, Anti-Histamines

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11
Q

Anaphylaxis

A

A severe systemic allergic reaction - respiratory diffculty and hypotension
IgE mediated mast cell degranulation - peanut, penicillin, stings, latex
Non- IgE mediated mast cell degranulation - NSAIDs, IV contrast, opiods, exercise

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12
Q

Management of Anaphylaxis

A

Elevate Legs, 100% Oxygen, IM adrenaline 500mcg, inhaled bronchodilators, Hydrocortisone 100mg IV, Chlorphenamine 10mg IV, IV fluids, Seek help

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13
Q

Investigations in allergy - Skin prick test

what is it used for? what is a positive test? anything that should be done before the test?

A

Useful to confirm clinical history. Negative test excludes IgE mediated allergy.
Positive control - histamine, negative control - dilutent
A positive test is a wheal > 2mm greater than the negative control
Discontinue antihistamines 48hrs before test (corticosteroids are ok)

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14
Q

Investigations in allergy - Quantitative specific IgE to putative allergen (RAST)
what it does? used for? sensitivity? indications?

A

Measure levels of IgE in serum against a particular allergen
Confirms dx of allergy and monitors response to anti-IgE treatment
Less sensitive/specific than skin prick testing
Indications - can’t stop anti-histamines, anaphylaxis, extensive eczema

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15
Q

Investigations in allergy - Component resolved diagnostics

A

Measures IgE response to a specific allergen protein (whilst conventional tests measure response to range of allergen proteins)

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16
Q

Investigations in allergy - Challenge test

A

Double blind oral food challenge in gold standard for food allergy BUT risk of severe reaction when testing.
Increasing volumes of offending food/drug are ingested under close supervision.

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17
Q

Investigations in allergy - During an acute episode

A

Measure mast cell tryptase (peak at 1-2hrs, baseline by 6hrs)

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18
Q

Type II Hypersensitivity Disorders

A

IgG or IgM antibody reacts with cell or matrix associated self antigen. Results in tissue damage, receptor blockade/ activation

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19
Q 
T2HD - Heamolytic Disease of the Newborn (HDN)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen- Antigens on neonatal erythrocytes
Pathology - Maternal IgG mediated retoculocytosis and anaemia
Diagnosis - Positive Direct Coombs Test
Treatment - Maternal Plasma exchange, exchange transfusion

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20
Q 
T2HD - Autoimmune Haemolytic Anaemia (+ ITP = Evan's Syndrome)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Numerous autoantigens e.g. Rh blood group Ag
Pathogen - Destruction of RBC by auto antibody + complement + FcR + phagocytes, anaemia
Diagnosis - Positive Direct Coombs Test, Anti Red Cell Ab
Treatment - Steroids

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21
Q 
T2HD - Autoimmune Thrombocytopenic Purpura
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Glycoprotein IIb/IIIa on platelets
Pathology - Bruising/ Bleeding (purpura)
Diagnosis - Anti platelet Antibody
Treatment - Steroids, IVIG, Anti D antibody, Splenectomy

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22
Q 
T2HD - Goodpasture's Syndome 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Non- Collagenous domain of basement membrane collagen IV
Pathology - Glomerulonephritis, pulmonary haemorrhage
Diagnosis - Anti GBM Ab, Linear Smooth IF staining of IgG deposits on BM
Treatment - Corticosteroids and Immunosuppression

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23
Q 
T2HD - Pemphigus vulgaris 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Epidermal Cadherin
Pathology - Non-tense blistering of skin and Bullae
Diagnosis - Direct immunofluoresence showing IgG
Treatment - Corticosteroids and Immunosuppression

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24
Q 
T2HD - Graves disease 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - TSH receptor
Pathology - Hyperthyroid
Diagnosis - Anti TSH-R Ab
Treatment - Carbimazole and Propylthiouracil

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25
Q 
T2HD - Myasthenia Gravis
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Acetylcholine receptor
Pathology - Fatiguable muscle weakness, Double Vision
Diagnosis - Anti- ACh-R Ab, abnormal EMG, Tensilion test
Treatment - Neostigmine, Pyridostigmine, (if serious use IVIG and Plasmaphoresis)

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26
Q 
T2HD - Acute Rheumatic Fever 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - M proteins on Group A strep
Pathology - Myocarditis, Arthritis, Sydenham’s Chorea
Diagnosis - Clinical, based on Jones Criteria
Treatment - Aspirin, Steroids and Penicillin

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27
Q 
T2HD - Pernicious Anaemia 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Intrinsic Factor and Gastric Parietal Cells
Pathology - decreased Hb, decreased B12
Diagnosis - Anti-gastric Parietal Cell Ab, Anti- IF Ab, Schilling Test
Treatment - Dietary B12 or IM B12

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28
Q 
T2HD - Churg-Strauss Syndrome (eGPA)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Medium and Small Vessel Vasculitis
Pathology - Allergy -> Asthma -> Systemic Disease (Male predominance)
Diagnosis - p-ANCA (against myeloperoxidase), Granulomas, Eosinophil, Granulomas
Treatment - Prednisolone, Azathioprine, Cyclophosphamide

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29
Q 
T2HD - Wegener's Granulomatosis (GPA)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Medium and Small Vessel Vasculitis
Pathology - Sinus Problems, Lung Cavitations + haemorrhage, Cresentic Glomerulonephritis
Diagnosis - cANCA (against Proteinase 3) granulomas
Treatment - Corticosteroids, cyclophosphamide, co-trimoxazole

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30
Q 
T2HD - Microscopic Polyangitis (MPA)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Pauci- immune necrotizing, small vessel vasculitis
Pathology - Purpura, lived, many different organs affected
Diagnosis - pANCA (against myeloperoxidase)
Treatment - Prednisolone, Cyclophosphamide or Azathioprine, plasmaphoresis

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31
Q 
T2HD - Chronic Urticaria 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Neducatuibs (NSAIDS), cold, food, pressure, Sun, Exercise, Insect stings, Bites and Idiopathic
Pathology - Persistent Itchy Wheals Lasting >6Weeks. Associated with Angioedema in 50% of cases. IgG against FcR1 or IgG against IgE (exclude urticarial vasculitis in those who respond poorly to anti-histamine)
Diagnosis - Challenge Test, ESR (Raised in Urticarial Vasculitis), Skin Prick Test
Treatment - Avoid precipitants, Check for Thyroid disease, Preventative antihistamine, IM adrenaline for pharyngeal angioedema, 1% Menthol in Aqueous Cream for Pruritis (also Doxepin and Cyclosporin)

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32
Q

T3HD

A

IgG or IgM immune complex (Ab or soluble Ag) mediated tissue damage

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33
Q 
T3HD - Mixed Essential Cryoglobulinaemia 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - IgM against IgG +/- hep C antigens
Pathology - Joint pain, splenomegaly, skin, nerve and kidney involvement. Associated with Hep C
Diagnosis - A mix of clinical and biopsies
Treatment - NSAIDs, Corticosteroids and plasmaphoresis

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34
Q 
T3HD - Serum Sickness
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Reaction to proteins in antiserum (Penicillin)
Pathology - Rashes, Itching, arthralgia, lymphadenopathy, fever and malaise. Symptoms take 7-12 days to develop
Diagnosis - Decreased C3. Blood shows immune complexes or signs of blood vessel inflammation
Treatment - Discontinuation of precipitant, steroids, antihistamines (+/- analgesia)

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35
Q 
T3HD - Polyarteritis Nodosa (PAN) 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Hep B, Hep C virus antigens
Pathology - Fever, fatigue, weakness, arthralgia, skin, nerve and kidney involvement, pericarditis and MI. Associated with Hep B
Diagnosis - Diagnosed by clinical criteria and biopsy (high EST, high WCC, high CRP) “Rosary sign”
Treatment - Prednisolone and Cyclophosphamide

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36
Q 
T3HD - Systemic Lupus Erythematosis (SLE)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Mainly intracellular components; DNA, histones, RNP
Pathology - M:F = 1:9, 4/11 of these - serositis, seizures, pathos ulcers, arthritis, photosensitivity, discoid rash, malar rash, haematology, kidney findings, Antinuclear antibody (ANA +ve), immunological findings (anti-dsDNA, anti-sm)
Diagnosis - low C4 (low C3 only in SEVERE disease) Ab’s to dsDNA, Histones (drug induced), Ro, La, Sm, U!RNP high ESR, normal CRP
Treatment - Mainly; Analgesia, steroids and cyclophosphamide

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37
Q

T4HD

A

Delayed hypersensitivity, T-cell mediated

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38
Q 
T4HD - Type 1 Diabetes Mellitus
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Pancreatic Beta Cell Proteins (glutamate Decarboxylase GAD)
Pathology - Insulitis, Beta cell destruction
Diagnosis - Blood Glucose, Ketonuria, Glutamate Decarboxylase Antibodies, Islet cell antibodies
Treatment - Insulin via injection or continuous infusion

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39
Q 
T4HD - Multiple Sclerosis
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Oligodendrocytes proteins (Myelin basic protein, Proteolipid protein)
Pathology - Demyelinating disease, preicascular inflammation, paralysis, Ocular lesions
Diagnosis - CSF shows Oligoclonal Bands or IgG on electrophoresis
Treatment - Corticosteroids, Interferon-beta

40
Q 
T4HD - Rheumatoid Arthritis (also type 3: IgM Ab vs Fc region of IgG)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Antigen in Synovial Membrane
Pathology - Chronic Arthritis, Rheumatoid Nodules, Lung Fibrosis
Diagnosis - X-Ray, Rheumatoid Factor (85% Sensitive), Anti-CCP (95% specific), high ESR and CRP
Treatment - Analgesia, Steroids, DMARDs

41
Q 
T4HD - Contact Dermatitis 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Environmental Chemicals, Poison Ivy, Nickel
Pathology - Dermatitis with usually short-lived itching, blisters and wheals
Diagnosis - Clinical or use Patch Test
Treatment - If no resolution use corticosteroids or antihistamines

42
Q 
T4HD - Mantoux Test 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Tuberculin

Pathology - Skin Induration indicates TB exposure

43
Q 
T4HD - Crohn's Disease
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Pathology - TH1 mediated. Chronic inflammation in skip lesions in GIT. NOD2 gene mutation in 30%
Diagnosis - Biopsy of lesion (can affect any part of GIT from mouth or anus)
Treatment - Antibiotics, anti-inflammatory drugs e.g. Mesalazine, TNF alpha antagonists e.g. infliximab, steroids

44
Q

HLA Associations - Ankylosing spondylitis

  • Susceptibility Alelle
  • Relative Risk (fold)
A
  • Susceptibility Alelle - HLA B27

- Relative Risk (fold) - 87

45
Q

HLA Associations - Goodpasture’s Syndrome

  • Susceptibility Alelle
  • Relative Risk (fold)
A
  • Susceptibility Alelle - HLA DR15/DR2

- Relative Risk (fold) - 10

46
Q

HLA Associations - Graves Disease

  • Susceptibility Alelle
  • Relative Risk (fold)
A
  • Susceptibility Alelle - HLA - DR3

- Relative Risk (fold) - 4

47
Q

HLA Associations - SLE

  • Susceptibility Alelle
  • Relative Risk (fold)
A
  • Susceptibility Alelle - HLA - DR3

- Relative Risk (fold) - 6

48
Q

HLA Associations - T1DM

  • Susceptibility Alelle
  • Relative Risk (fold)
A
  • Susceptibility Alelle - HLA DR3/DR4

- Relative Risk (fold) - 25

49
Q

HLA Associations - Rheumatoid Arthritis

  • Susceptibility Alelle
  • Relative Risk (fold)
A
  • Susceptibility Alelle - HLA-DR4

- Relative Risk (fold) - 4

50
Q

PTPN22

A

Tyrosine phosphatase expressed in lymphocytes, associated development of RA, SLE, and T1DM

51
Q

CTLA4

A

receptor for CD80/CD86 expressed by T cells, transmits inhibitory signal to control T cell activation, Associated with SLE, T1DM, Autoimmune thyroid disease

52
Q

CREST syndrome - Limited Cutaneous Scleroderma

- what does CREST stand for

A 
Calcinosis
Raynaud's 
(O)Esophageal dysmotility
Sclerodactyly
Telangiectasia
(+ primary pulmonary hypertension)
53
Q

Diffuse Cutaneous Scleroderma

- what does it involve?

A

CREST + GIT+ interstitial pulmonary disease + renal problems

54
Q

Sjogren’s Syndrome

- who is affected?

A

M:F 1:9, onset in late 40s

55
Q

IPEX syndrome

- what does it stand for?

A

Immune dysregulation,
Polyendocrinopathy,
Enteropathy and
X-linked inheritance syndrome + autoimmune diseases

56
Q

Sjogren’s Syndrome

- symptoms?

A

Dry mouth (xerostomia), eyes (keratoconjunctivitis sicca), nose and skin
May affect kidneys, blood vessels, lungs, liver, pancreas and PNS, may get parotid or salivary gland enlargement
Anti-Ro and anti-La antibodies present
Use Schirmer test to measure production of tears- assessing for dry eyes

57
Q

Sjogren’s Syndrome

- Ab present?

A

Anti-Ro and anti-La antibodies present

Use Schirmer test to measure production of tears- assessing for dry eyes

58
Q

Sjogren’s Syndrome

- what test is used?

A

Use Schirmer test to measure production of tears- assessing for dry eyes

59
Q

IPEX syndrome

-Symptoms?

A

Eczematous dermatitis, nail dystrophy and autoimmune skin conditions such as alopecia universals and bullous pemphigoid

60
Q

IPEX syndrome

-age of death?

A

Most affected children die within the first 2 years of life

61
Q

IPEX syndrome

-inheritance?

A

X-linked recessive disorder with exclusive expression in males

62
Q

IPEX syndrome

-treatment?

A

Bone marrow transplant is the only cure. can use immunomodulators to help

63
Q

CREST syndrome - Limited Cutaneous Scleroderma

  • Antibodies for diagnosis
  • increases risk for what?
A

Anti-centromere Antibodies for diagnosis

64
Q

CREST syndrome - Limited Cutaneous Scleroderma

-increases risk for what?

A

High risk of Lung Fibrosis and Renal Crisis

65
Q

Diffuse Cutaneous Scleroderma

- Antibodies?

A

Anti- Topoisomerase/ Scl70, RNA Pol 1,2 and 3, Fibrillarin Antibodies

66
Q

Diffuse Cutaneous Scleroderma

- who is affected?

A

Females: males 4:1

67
Q

Coeliac Disease

-what is it?

A

Failure of tolerance to gluten. Villous atrophy and enteropathy

68
Q

Coeliac Disease

-Symptoms?

A

GIT discomfort, constipation, diarrhoea, bloating, fatigue

69
Q

Coeliac Disease

-what does it go on to cause deficiencies in?

A

Iron, B12, Folate, Fat, Vitamins A, D, E & K and calcium deficiencies

70
Q

Coeliac Disease

-Immunogloblins involved?

A 
IgA EMA (anti- endomysial antibody) disappears with exclusion diet (95% specific, 85% sensitive)
IgA TGT (anti- transglutaminase antibody) - 95% specific, 90-94% sensitive
IgG anti-gliadin antibody - most persistent (30-50% specific, 57-80% sensitive)
71
Q

Coeliac Disease

-Test

A

Gold Standard test is to do a duodenal biopsy but it is not first line

72
Q

What autoantibody is associated with … Antiphospholipid Syndrome (Hugh’s syndrome) ?

A

IgG Antibodies against cardiolipin and beta2 glycoprotein, lupus anticoagulant

73
Q

What autoantibody is associated with …Autoimmune Hepatitis?

A

IgG - Anti-smooth muscle antibody, anti-liver kidney microsomal-1 (anti-LKM-1). Anti Soluble Liver antigen (anti-SLA)

74
Q

What autoantibody is associated with …Autoimmune haemolytic anaemia?

A

IgG- Anti-Rh blood group antigen

75
Q

What autoantibody is associated with … Autoimmune Thrombocytopenic Purpura?

A

IgG - Anti-Glycoprotein IIb-IIIa or Ib-IX antibody

76
Q

What autoantibody is associated with … Churg-Strauss Syndrome (eGPA)?

A

Perinuclear/protoplasmic-stainng antineutrophil cytoplasmic antibodies (p-ANCA)

77
Q

What autoantibody is associated with … Coeliac disease?

A

IgA - Anti-tissue transglutaminase antibody, Anti-endomysial antibody

78
Q

What autoantibody is associated with … Congenital heart block in infants of mothers with SLE?

A

IgG - Anti-Ro antibody

79
Q

What autoantibody is associated with … Dermatitis hepetiformis?

A

IgA - anti-endomysial antibody

80
Q

What autoantibody is associated with …Dermatomyositis?

A

IgG - Anti-Jo-1 (t-RNA Synthetase)

81
Q

What autoantibody is associated with … Diffuse Cutaneous Scleroderma?

A

IgG - Antibodies to Topoisomerase/Scl70, RNA Pol I, II, III, Fibrillarin (nucleolar pattern)

82
Q

What autoantibody is associated with … Goodpasture’s Syndrome?

A

IgG - Anti-GBM antibody

83
Q

What autoantibody is associated with …Graves Disease?

A

IgG - Anti-TSH Receptor antibody (stimuatory antibody)

84
Q

What autoantibody is associated with … Hashimoto’s Thyroiditis?

A

IgG - Antibodies to Thyroiglobulin and thyroperoxidase

85
Q

What autoantibody is associated with … Limited Cutaneous scleroderma (CREST)

A

IgG - Anti-centromere antibody

86
Q

What autoantibody is associated with … Microscopic Polyangitis (MPA)?

A

IgG- Perinuclear.protoplasmic-staining antineutrophil cytoplasmic antibodies (p-ANCA)

87
Q

What autoantibody is associated with … Mixed connective tissue disease?

A

IgG- Anti-U1RNP antibody (speckled pattern)

88
Q

What autoantibody is associated with … Myasthenia Gravis?

A

IgG- Anti-ACh Receptor Antibody

89
Q

What autoantibody is associated with … Pernicious anaemia?

A

IgG - Antibodies to gastric parietal cells (90%) and intrinsic factor (50%)

90
Q

What autoantibody is associated with … Polymyositis?

A

IgG - Anti-Jo-1 (t-RNA Synthetase)

91
Q

What autoantibody is associated with … Primary Biliary Cirrhosis?

A

IgG- Anti-mitochondrial antibody

92
Q

What autoantibody is associated with … Rheumatoid Arthritis?

A

IgG- Anti-CCP antibodies, Rheumatoid factor

93
Q

What autoantibody is associated with … Sjogren’s Sundrome?

A

IgG - Anti-Ro, Anti-La antibody (speckled pattern), 60-70% have positive RF

94
Q

What autoantibody is associated with … Systemic Lupus Erthematosis?

A

IgG - Antibodies to dsDNA+ histones (Homogenous) and Ro LA, Sm, U1RNP (speckled)

95
Q

What autoantibody is associated with … Type 1 Diabetes Mellitus?

A

IgG - Antibodies to Glutamate Decarboxylase and pancreatic beta cells

96
Q

What autoantibody is associated with … Wegener’s Granulomatosis (GPA)?

A

IgG - Cytoplasmic antinutrophil cytoplasmic antibodies (c-ANCA)

Path Immunology (8 decks)

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