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Pathology (Guide) > Immunology - Hypersensitivity Disorders > Flashcards

Immunology - Hypersensitivity Disorders Flashcards

1
Q

What are Type 1 Hypersensitivity reactions?

A
  • Immediate reaction provoked by re-exposure to an antigen
  • IgE-mediated: Mast cells release mediators resulting in vasdilation, increased permeability, smooth muscle spasm
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2
Q

What are some typical Sx of a Type 1 Hypersenstivity reaction?

A
  • Angioedema
  • Urticaria
  • Rhino conjunctivitis
  • Wheeze
  • D+V
  • ANAPHYLAXIS
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3
Q

What happens on first and second exposure in a Type 1 Hypersensitivity reaction?

A

First Exposure: Sensitisation
- Th2 cells primed by APCs in LN
- Cytokine release (IL4 + IL5)

Second Exposure: Allergy
- Primed mast cells degranulate
- Histamine = key mediator
- Ag cross-links IgE on mast cells resulting in degranulation

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4
Q

What is the atopic triad?

A
  • Eczema
  • Asthma
  • Hay fever
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5
Q

What are the allergens in atopic dermatitis (infantile eczema)?

A
  • Irritants
  • Food
  • Environmental
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6
Q

What is the pathology of atopic dermatitis (infantile eczema)?

A

Defects in β defensin predisposes to S. aureus superinfection

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7
Q

How is atopic dermatitis diagnosed?

A

Clinical
- 80% present in first year of life

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8
Q

How is atopic dermatitis managed?

A
  • Emollients
  • Skin oils
  • Topical steroids
  • Abx
  • PUVA phototherapy
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9
Q

What are the typical allergens for a food allergy?

A
  • Milk
  • Egg
  • Peanuts
  • Tree nuts
  • Fish
  • Shellfish
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10
Q

What is the pathology of a food allergy?

A
  • IgE (anaphylaxis)
  • Cell mediated (Coeliac)
  • IgE/Cell mediated (atopic dermatitis)
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11
Q

How is a food allergy diagnosed?

A
  • Food diary
  • Skin prick tests
  • RAST
  • Challenge test

Most resolve by adulthood

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12
Q

What is the treatment for a food allergy?

A
  • Dietician
  • Food avoidance
  • EpiPen
  • Control asthma if present
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13
Q

What are some allergens for Oral Allergy Syndrome (OAS)?

A
  • Birch pollen + rosacea fruit
  • Ragweed + melons
  • Mugwort + Celery

Cross-reactivity

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14
Q

What is the pathology of an oral allergy syndrome?

A
  • Exposure to allergen induces allergy to food
  • Sx limited to mouth (2% get anaphylaxis)
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15
Q

How is Oral Allergy syndrome diagnosed?

A
  • Clinical Dx
  • Skin prick testing can be helpful
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16
Q

How is Oral Allergy Syndrome Treated?

A
  • Avoid food

IF ingested:
- Wash mouth
- Take antihistamine

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17
Q

What are some allergens for latex food syndrome?

A
  • Chestnut
  • Avocado
  • Banana
  • Potato
  • Tomato
  • Kiwi
  • Papaya
  • Eggplant
  • Mango
  • Wheat
  • Melon
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18
Q

What is the pathology of a latex food syndrome?

A
  • Some foods have latex-like components
  • Latex allergy sufferers also have food allergies
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19
Q

How is latex food syndrome diagnosed?

A

Skin prick test

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20
Q

What is the treatment for latex food allergy?

A

Strict avoidance of causative food

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21
Q

What are some allergens for Allergic rhinitis?

A

Seasonal
- Tree + grass pollen
- Fungal spores

Perennial
- Pets
- House dust mite

Occupational:
- Latex
- Lab animals

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22
Q

What are some Sx of allergic rhinitis?

A
  • Nasal itch + obstruction
  • Sneezing
  • Anosmia
  • Eye Sx
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23
Q

How is allergic rhinitis diagnosed?

A
  • Pale bluish nasal mucosa
  • Skin prick test + RAST
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24
Q

What is the treatment for allergic rhinitis?

A
  • Allergen avoidance
  • Antihistamine
  • Steroid nasal spray
  • Sodium Cromoglycate Eye drops
  • Oral steroids
  • Ipatropium nasal spray
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25
Q

What are the causes of acute urticaria?

A
  • 50% idopathic
  • 50% caused by food, drugs, latex, viral infections, febrile illnesses
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26
Q

What is the pathology of acute urticaria?

A
  • IgE mediated reaction
  • Wheals (completely resolve in 6 weeks)
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27
Q

How is acute urticaria diagnosed?

A

Clinical
- ?Skin prick test

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28
Q

How is acute urticaria treated?

A
  • Allergen avoidance
  • Antihistamines
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29
Q

What is anaphylaxis?

A

A severe systemic allergic reaction
- Respiratory difficulty + hypotension

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30
Q

What allergens lead to IgE-medaited mast cell degranulation in anaphylaxis?

A
  • Peanut
  • Penicillin
  • Stings
  • Latex
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31
Q

What allergens lead to non-IgE-mediated mast cell degranulation in anaphylaxis?

A
  • NSAIDs
  • IV contrast
  • Opioids
  • Exercise
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32
Q

What are some differential diagnoses for anaphylaxis?

A
  • C1 inhibitor deficiency - hereditary angioedema
  • ACEi induced angioedema
  • Acute anxiety
  • Urticaria
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33
Q

What is the management for anaphylaxis?

A
  • A-E + Stop trigger
  • Elevate legs
  • 100% oxygen
  • IM Adrenaline (1:1000) 500ug (adult)
  • Inhaled bronchodilators
  • IV fluids
  • Seek help
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34
Q

What are some investigations used for allergy testing?

A
  • Skin prick tests
  • Quantitative specific IgE to putative allergen (RAST)
  • Component-resolved diagnostics
  • Challenge test
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35
Q

How does a Skin Prick Test work?

A
  • Negative test excludes IgE mediated allergy
  • Positive control = histamine
  • Negative control = dilutant
  • Positive result = Wheal >=2mm greater than negative control
  • Discontinue antihistamines 48hrs prior to test (corticosteroids ok)
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36
Q

How does a quantitative specific IgE to putative allergen (RAST) test work?

A
  • Measures levels of IgE in serum against particular allergen (e.g. peanuts)
  • Confirms Dx of allergy + monitors response to IgE treatment
  • Less sensitive + specific than skin prick testing
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37
Q

What are some indications for RAST testing?

A
  • Can’t stop antihistamines
  • Anaphylaxis Hx
  • Extensive eczema
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38
Q

How doe component-resolved diagnostics work?

A
  • Measures IgE response to specific allergen protein (conventional tests measure response to range of allergen proteins)
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39
Q

How does a challenge test work?

A
  • Double-blind oral food challenge
  • Increasing volumes of offending food/drug ingested under close supervision
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40
Q

What is a risk to a Challenge test?

A

Severe reaction when testing (anaphylaxis)

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41
Q

What is the gold standard test for Food allergy testing?

A

Challenge test

42
Q

What can be measured during an acute anaphylactic episode to confirm its presence?

A

Mast Cell tryptase
- Peaks at 1-2hrs
- Baseline by 6hrs

43
Q

What is a type 2 hypersensitivity reaction?

A
  • IgG or IgM antibody reacts with cell or matrix associated self-antigen
  • Results in tissue damage, receptor blockade, activation
44
Q

What happens during antibody dependent cytotoxicity?

A
  • Phagocytosis
  • Complement + MAC activation - leading to cell lysis
  • Cytolytic granules released
45
Q

What are the antigens associated with haemolytic disease of the newborn, its pathology, diagnosis and treatment?

A

Ag:
- Ag on neonatal erythrocytes

Path:
- Maternal IgG mediated reticulocytosis + anaemia

Dx:
- +ve Direct Coombs Test

Tx:
- Maternal plasma exchange
- Exchange transfusion

46
Q

What are the antigens associated with autoimmune haemolytic anaemia, its pathology, diagnosis and treatment?

A

Ag:
- Numerous autoantigens (e.g. Rh blood group Ag)

Path:
- Destruction of RBCs by autoantibody + complement + FcR + phagocytes
- Anaemia

Dx:
- +ve Direct Coombs Test
- Anti RBC Ag

Tx:
- Steroids

47
Q

What are the antigens associated with Autoimmune thrombocytopenic purpura, its pathology, diagnosis and treatment?

A

Ag:
- Glycoprotein IIb/IIIa on plts

Path:
- Bruising/bleeding

Dx:
- Anti-plt Ab

Tx:
- Steroids
- IVIG
- Anti-D Ab
- Splenectomy

48
Q

What are the antigens associated with Goodpasture’s Syndrome, its pathology, diagnosis and treatment?

A

Ag:
- Non-collagenous domain of basement membrane collagen Type IV

Path:
- Glomerulonephritis
- Pulmonary haemorrhage

Dx:
- Anti GBM Ab
- Linear smooth IF staining of IgG deposits on BM

Tx:
- Corticosteroids
- Immunosuppression

49
Q

What are the antigens associated with pemphigus vulgaris, its pathology, diagnosis and treatment?

A

Ag:
- Epidermal cadherin

Path:
- Non-tense blistering of skin + bullae

Dx:
- Direct immunofluorescence showing IgG deposition

Tx:
- Corticosteroids
- Immunosuppression

50
Q

What are the antigens associated with Graves’ Disease, its pathology, diagnosis and treatment?

A

Ag:
- TSH receptor

Path:
- Hyperthyroidism

Dx:
- Anti-TSH-R Ab

Tx:
- Carbimazole
- Propylthiouracil

51
Q

What are the antigens associated with Myasthenia Gravis, its pathology, diagnosis and treatment?

A

Ag:
- Acetylcholine receptor

Path:
- Fatiguable muscle weakness
- Double vision

Dx:
- Anti-ACh-R Ab
- Abnormal EMG
- Tensilon Test

Tx:
- Neostigmine
- Pyridostigmine
(IF serious = IVIG + plasmapheresis)

52
Q

What are the antigens associated with Acute Rheumatic Fever, its pathology, diagnosis and treatment?

A

Ag:
- M proteins on Group A strep

Path:
- Mycocarditis
- Arthritis
- Sydenham’s Chorea

Dx:
- Clinical
- Based on Jones Criteria

Tx:
- Aspirin
- Steroids
- Penicillin

53
Q

What are the antigens associated with Pernicious Anaemia, its pathology, diagnosis and treatment?

A

Ag:
- Intrinsic Factor
- Gastric Parietal Cells

Path:
- Decreased Hb
- Decreased B12

Dx:
- Anti-gastric parietal cell Ab
- Anti-IF Ab
- Schilling Test

Tx:
- Dietary B12/IM B12

54
Q

What are the antigens associated with Churg-Strauss Syndrome (eGPA), its pathology, diagnosis and treatment?

A

Ag:
- Medium small vessel vasculitis

Path:
- Allergy leads to asthma leads to systemic disease
- Male ppredominance

Dx:
- p-ANCA (against myeloperoxidase)
- Granulomas
- Eosinophil granulocytes

Tx:
- Prednisolone
- Azathioprine
- Cyclophosphamide

55
Q

What are the antigens associated with Wegener’s Granulomatosis (GPA), its pathology, diagnosis and treatment?

A

Ag:
- Medium + small vessel vasculitis

Path:
- Sinus problems
- Lung cavitations + haemorrhage
- Crescenteric glomerulonephritis

Dx:
- c-ANCA (against Proteinase 3) granulomas

Tx:
- Corticosteroids
- Cyclophosphamide
- Co-trimoxazole

56
Q

What are the antigens associated with microscopic polyangiitis, its pathology, diagnosis and treatment?

A

Ag:
- Pauci-immune necrotising
- Small vessel vasculitis

Path:
- Purpura
- Livedo
- Many different organs affected

Dx:
- p-ANCA (against myeloperoxidase)

Tx:
- Prednisolone
- Cyclophosphamide / Azathioprine
- Plasmapharesis

57
Q

What are the antigens associated with chronic urticaria, its pathology, diagnosis and treatment?

A

Ag:
- Medications (NSAIDS)
- Cold
- Food
- Pressure
- Sun
- Exercise
- Insect Stings
- Bites
- Idiopathic

Path:
- Persistent itchy wheals last >6wks
- A/w angioedema (50%)
- IgG against FceR1 or IgG against IgE

Dx:
- Challenge test
- ESR (raised)
- Skin prick testing

Tx:
- Avoid precipitants
- Check for thyroid disease
- Preventative anti-histamine
- IM adrenaline for pharyngeal angioedema
- 1% Menthol in aqueous cream for pruritis

58
Q

What are type 3 hypersensitivity disorders?

A

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

59
Q

What are the antigens associated with Mixed Essential Cryoglobinaemia, its pathology, diagnosis and treatment?

A

Ag:
- IgM against IgG +/- Hep C Ags

Pathology:
- Joint pain
- Splenomegaly
- Skin, nerve + kidney involvement
- A/w Hep C

Dx:
- A mixture of clinical + biopsies

Tx:
- NSAIDs
- Corticosteroids
- Plasmapheresis

60
Q

What are the antigens associated with Serum Sickness, its pathology, diagnosis and treatment?

A

Ag:
- Rx to proteins in antiserum (penicillin)

Path:
- Rashes
- Itching
- Arthralgia
- Lymphadenopathy
- Fevers
- Malaise
- Sx take 7-12/7 to develop

Dx:
- Decreased C3
- Blood shows immune complexes or signs of blood vessel inflammation

Tx:
- Discontinuation of precipitant
- Steroids
- Antihistamines
- +/- Analgesia

61
Q

What are the antigens associated with Polyarteritis Nodosa, its pathology, diagnosis and treatment?

A

Ag:
- Hep B (surface Ag)
- Hep C virus Ag

Path:
- Fever
- Fatigue
- Weakness
- Arthralgia
- Skin, nerve + kidney involvement
- Pericarditis
- MI
- A/w: Hep B

Dx:
- Dx by clinical criteria + biopsy
- Raised ESR, WCC + CRP

Tx:
- Prednisolone
- Cyclophosphamide

62
Q

What are the antigens associated with Systemic Lupus erythematosis (SLE), its pathology, diagnosis and treatment?

A

Ag:
- Mainly intracellular components (DNA, Histones, RNP)

Pathology:
- M:F = 1:9
- 4 of: serositis, seizures, aphthous ulcers, arthritis, photosensitivity, discoid rash, malar rash, haematology, kidney findings ANA-Ab, immunological findings (anti-dsDNA, anti-SM)

Dx:
- Decreased C4 (Decreased C3 only in severe disease)
- Abs to dsDNA, histones, Ro, La, SM, U1RNP
- Increased ESR, normal CRP

Tx:
- Analgesia
- Steroids
- Cyclophosphamide

63
Q

How do HLA-CD8 complexes damage cells?

A

Via perforin or Fas

64
Q

How do HLA-CD4 complexes damage cells?

A

Via TNF + cytokine production, lymphotoxin, HLA upregulation

65
Q

What is a type 4 hypersensitivity reaction?

A
  • Delayed hypersensitivity
  • T-cell mediated
66
Q

What are the antigens associated with T1DM, its pathology, diagnosis and treatment?

A

Ag:
- Pancreatic β cell proteins (glutamate decarboxylase GAD)

Path:
- Insulinitis
- β cell destruction

Dx:
- Blood glucose
- Ketonuria
- Glutamate decarboxylase Abs
- Islet cell Abs

Tx:
- Insulin via injections or continous infusion

67
Q

What are the antigens associated with Multiple sclerosis, its pathology, diagnosis and treatment?

A

Ag:
- Oligodendrocyte proteins (Myelin basic protein, proteolipid protein)

Path:
- Demyelinating disease
- Perivascular inflammation
- Paralysis
- Ocular lesions

Dx:
- CSF shows OLIGOCLONAL BANDS of IgG on electrophoresis

Tx:
- Corticosteroids
- Interferon β

68
Q

What are the antigens associated with Rheumatoid arthritis, its pathology, diagnosis and treatment?

A

Ag:
- Ag in synovial membrane

Path:
- Chronic arthritis
- Rheumatoid nodules
- Lung fibrosis

Dx:
- X-ray
- Rheumatoid factor
- Anti-CCP
- Increased ESR + CRP

Tx:
- Analgesia
- Steroids
- DMARDs

69
Q

What are the antigens associated with contact dermatitis, its pathology, diagnosis and treatment?

A

Ag:
- Environmental chemicals, poison ivy, nickel

Path:
- Dermatitis with usually short-lived itching, blisters, wheals

Dx:
- Clinical or use patch test

Tx:
- If no resolution use corticosteroids or antihistamines

70
Q

What are the antigens associated with mantoux tests and its pathology?

A

Ag:
- tuberculin

Path:
- Skin induration indicates TB exposure

71
Q

What is the pathology of Crohn’s disease, its diagnosis and treatment?

A

Path:
- Th1 mediated
- Chronic inflammation in skin lesions in GIT
- NOD2 gene mutation in 30%

Dx:
- Biopsy of lesion

Tx:
- Abx
- Anti-inflammatory drugs (e.g. mesalazine, TNF-α antagonists e.g. infliximab)
- Steroids

72
Q

What are some features of CREST syndrome (limited cutaneous scleroderma) + its Abs for Dx?

A
  • Calcinosis, Raynaud’s, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
    • primary pulmonary HTN
  • Skin involvement up to forearms only + perioral
  • High risk for lung fibrosis + renal crisis

Dx: Anti-Centromere Abs

73
Q

What are some features of diffuse cutaneous scleroderma + its Abs for Dx?

A
  • CREST + GIT + Interstitial pulmonary disease + renal problems
  • F:M = 4:1

Anti-topoisomerase/Scl70, RNA pol 1, 2, 3, fibrillarin Abs

74
Q

What are some features of Sjogren’s Syndrome + its Abs for Dx?

A
  • M:F = 1:9
  • Onset in late 40s
  • Dry mouth, eyes, nose + skin
  • May affect kidneys, blood vessels, lungs, liver, pancreas + PNS
  • ?Parotid/salivary gland enlargement
  • Schirmer test = measure production of tears (assessing for dry eyes)

Dx: Anti-Ro + Anti-La Abs

75
Q

What are some features of IPEX syndrome?

A
  • Immune dysregulation, Polyendocrinopathy, Enteropathy + X-linked inheritance syndrome + autoimmune diseases
  • Eczematous dermatitis, nail dystrophy + AI skin conditions (e.g. alopecia universalis + bullous pemphigoid)
  • Most affected children die within first 2 years of life
  • X-linked recessive (exclusive expression in males)
  • Tx: Bone marrow transplant (only cure)
76
Q

What are some features of Coeliac Disease + its Abs for Dx?

A
  • Failure of tolerance to gluten
  • Villous atrophy + enteropathy
  • GIT discomfort, constipation, diarrhoea, bloating + fatigue
  • Iron, B12, Fat, Vit ADEK + Ca deficiencies
  • IgA EMA (anti-endomyial Ab)
  • IgA TGT (anti-tranglutaminase Ab)
  • IgG anti-gliadin Ab
  • DERMATITIS HERPETIFORMIS
  • Links to Down’s syndrome
  • Ireland = EMA, North Africa = TGT

Gold-standard = Duodenal biopsy (not first-line)

95% have DQ2 or DQ8 (Two eight or not to eat)

77
Q

What are the autoantibodies associated with APLS?

A
  • Anti-cardiolipin
  • Anti-β2 glycoprotein
  • lupus anticoagulant
78
Q

What are the autoantibodies associated with autoimmune hepatitis?

A
  • Anti-smooth muscle antibody
  • Anti Liver Kidney Microsomal-1
  • Anti-soluble liver antigen
79
Q

What are the autoantibodies associated with AIHA?

A
  • Anti- Rh Blood Group Antigen
80
Q

What are the autoantibodies associated with AITP?

A
  • Anti-glycoprotein IIb-IIIa Ab
  • Anti-glycoprotein Ib-IX Ab
81
Q

What are the autoantibodies associated with Churg-Strauss Syndrome?

A
  • perinuclear/protoplasmic-staining antineutrophil cytoplasmic antibody (p-ANCA)
82
Q

What are the autoantibodies associated with coeliac disease?

A
  • Anti-tissue tranglutaminase Ab (IgA)
  • Anti-endomysial antibody (IgA)
83
Q

What are the autoantibodies associated with congenital heart block in infants of mothers with SLE?

A
  • Anti-Ro Ab
84
Q

What are the autoantibodies associated with dermatitis herpetiformis?

A
  • Anti-endomysial Ab (IgA)
85
Q

What are the autoantibodies associated with Dermatomyositis?

A
  • Anti-Jo-1 (t-RNA synthetase)
86
Q

What are the autoantibodies associated with Diffuse cutaneous scleroderma?

A
  • Abs to topoisomerase/Scl70
  • Abs to RNA pol I, II, III
  • Abs to Fibrillarin (nuclear pattern)
87
Q

What are the autoantibodies associated with Goodpasture’s syndrome?

A
  • Anti-GBM Ab
  • TYPE IV COLLAGEN
88
Q

What are the autoantibodies associated with Graves’ Disease?

A
  • Anti-TSH receptor Ab
89
Q

What are the autoantibodies associated with Hashimoto’s thyroiditis?

A
  • Abs to thyroglobulin
  • Abs to thyroperoxidase
90
Q

What are the autoantibodies associated with CREST syndrome (limited cutaneous scleroderma)?

A
  • Anti-centromere Ab
91
Q

What are the autoantibodies associated with Microscopic Polyangiitis (MPA)?

A
  • Perinuclear/protoplasmic-staining antineutrophil cytoplasmic Abs (p-ANCA)
92
Q

What are the autoantibodies associated with Mixed Connective Tissue Disease?

A
  • Anti-U1RNP Ab (speckled pattern)
93
Q

What are the autoantibodies associated with Myasthenia Gravis?

A
  • Anti-ACh-receptor Ab
  • Anti-MUSK
  • Anti-VGCC (Lambert-Eaton)
94
Q

What are the autoantibodies associated with Pernicious Anaemia?

A
  • Ab to gastric parietal cells
  • Abs to Intrinsic Factor
95
Q

What are the autoantibodies associated with Polymyositis?

A
  • Anti-Jo-1 (t-RNA synthetase)
96
Q

What are the autoantibodies associated with Primary biliary cirrhosis?

A
  • Anti-mitochondrial Ab
97
Q

What are the autoantibodies associated with Rheumatoid Arthritis?

A
  • Anti-CCP
  • Anti-rheumatoid factor (less specific)
98
Q

What are the autoantibodies associated with Sjogren’s Syndrome?

A
  • Anti-Ro Abs
  • Anti-La Abs (speckled pattern)
  • +ve RH
99
Q

What are the autoantibodies associated with Sjogren’s Syndrome?

A
  • Anti-Ro Abs
  • Anti-La Abs (speckled pattern)
  • +ve RF
100
Q

What are the autoantibodies associated with SLE?

A
  • Abs to dsDNA
  • Abs to histones (homogenous)
  • Abs to Ro
  • Abs to La
  • Abs to SM
  • Abs to U1RNP (speckled)
101
Q

What are the autoantibodies associated with T1DM?

A
  • Abs to glutamte decarboxylase
  • Abs to pancreative β cells
102
Q

What are the autoantibodies associated with Wegener’s Granulomatosis?

A
  • Cytoplasmic anti-neutrophil cytoplasmic Abs (c-ANCA)

Pathology (Guide) (84 decks)

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