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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
What are the causes of acute urticaria?
- 50% idopathic - 50% caused by food, drugs, latex, viral infections, febrile illnesses
26
What is the pathology of acute urticaria?
- IgE mediated reaction - Wheals (completely resolve in 6 weeks)
27
How is acute urticaria diagnosed?
Clinical - ?Skin prick test
28
How is acute urticaria treated?
- Allergen avoidance - Antihistamines
29
What is anaphylaxis?
A severe systemic allergic reaction - Respiratory difficulty + hypotension
30
What allergens lead to IgE-medaited mast cell degranulation in anaphylaxis?
- Peanut - Penicillin - Stings - Latex
31
What allergens lead to non-IgE-mediated mast cell degranulation in anaphylaxis?
- NSAIDs - IV contrast - Opioids - Exercise
32
What are some differential diagnoses for anaphylaxis?
- C1 inhibitor deficiency - hereditary angioedema - ACEi induced angioedema - Acute anxiety - Urticaria
33
What is the management for anaphylaxis?
- A-E + Stop trigger - Elevate legs - 100% oxygen - IM Adrenaline (1:1000) 500ug (adult) - Inhaled bronchodilators - IV fluids - Seek help
34
What are some investigations used for allergy testing?
- Skin prick tests - Quantitative specific IgE to putative allergen (RAST) - Component-resolved diagnostics - Challenge test
35
How does a Skin Prick Test work?
- 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)
36
How does a quantitative specific IgE to putative allergen (RAST) test work?
- 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
37
What are some indications for RAST testing?
- Can't stop antihistamines - Anaphylaxis Hx - Extensive eczema
38
How doe component-resolved diagnostics work?
- Measures IgE response to specific allergen protein (conventional tests measure response to range of allergen proteins)
39
How does a challenge test work?
- Double-blind oral food challenge - Increasing volumes of offending food/drug ingested under close supervision
40
What is a risk to a Challenge test?
Severe reaction when testing (anaphylaxis)
41
What is the gold standard test for Food allergy testing?
Challenge test
42
What can be measured during an acute anaphylactic episode to confirm its presence?
Mast Cell tryptase - Peaks at 1-2hrs - Baseline by 6hrs
43
What is a type 2 hypersensitivity reaction?
- IgG or IgM antibody reacts with cell or matrix associated self-antigen - Results in tissue damage, receptor blockade, activation
44
What happens during antibody dependent cytotoxicity?
- Phagocytosis - Complement + MAC activation - leading to cell lysis - Cytolytic granules released
45
What are the antigens associated with haemolytic disease of the newborn, its pathology, diagnosis and treatment?
Ag: - Ag on neonatal erythrocytes Path: - Maternal IgG mediated reticulocytosis + anaemia Dx: - +ve Direct Coombs Test Tx: - Maternal plasma exchange - Exchange transfusion
46
What are the antigens associated with autoimmune haemolytic anaemia, its pathology, diagnosis and treatment?
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
What are the antigens associated with Autoimmune thrombocytopenic purpura, its pathology, diagnosis and treatment?
Ag: - Glycoprotein IIb/IIIa on plts Path: - Bruising/bleeding Dx: - Anti-plt Ab Tx: - Steroids - IVIG - Anti-D Ab - Splenectomy
48
What are the antigens associated with Goodpasture's Syndrome, its pathology, diagnosis and treatment?
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
What are the antigens associated with pemphigus vulgaris, its pathology, diagnosis and treatment?
Ag: - Epidermal cadherin Path: - Non-tense blistering of skin + bullae Dx: - Direct immunofluorescence showing IgG deposition Tx: - Corticosteroids - Immunosuppression
50
What are the antigens associated with Graves' Disease, its pathology, diagnosis and treatment?
Ag: - TSH receptor Path: - Hyperthyroidism Dx: - Anti-TSH-R Ab Tx: - Carbimazole - Propylthiouracil
51
What are the antigens associated with Myasthenia Gravis, its pathology, diagnosis and treatment?
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
What are the antigens associated with Acute Rheumatic Fever, its pathology, diagnosis and treatment?
Ag: - M proteins on Group A strep Path: - Mycocarditis - Arthritis - Sydenham's Chorea Dx: - Clinical - Based on Jones Criteria Tx: - Aspirin - Steroids - Penicillin
53
What are the antigens associated with Pernicious Anaemia, its pathology, diagnosis and treatment?
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
What are the antigens associated with Churg-Strauss Syndrome (eGPA), its pathology, diagnosis and treatment?
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
What are the antigens associated with Wegener's Granulomatosis (GPA), its pathology, diagnosis and treatment?
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
What are the antigens associated with microscopic polyangiitis, its pathology, diagnosis and treatment?
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
What are the antigens associated with chronic urticaria, its pathology, diagnosis and treatment?
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
What are type 3 hypersensitivity disorders?
IgG or IgM immune complexes (Ab vs soluble Ag) mediated tissue damage
59
What are the antigens associated with Mixed Essential Cryoglobinaemia, its pathology, diagnosis and treatment?
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
What are the antigens associated with Serum Sickness, its pathology, diagnosis and treatment?
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
What are the antigens associated with Polyarteritis Nodosa, its pathology, diagnosis and treatment?
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
What are the antigens associated with Systemic Lupus erythematosis (SLE), its pathology, diagnosis and treatment?
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
How do HLA-CD8 complexes damage cells?
Via perforin or Fas
64
How do HLA-CD4 complexes damage cells?
Via TNF + cytokine production, lymphotoxin, HLA upregulation
65
What is a type 4 hypersensitivity reaction?
- Delayed hypersensitivity - T-cell mediated
66
What are the antigens associated with T1DM, its pathology, diagnosis and treatment?
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
What are the antigens associated with Multiple sclerosis, its pathology, diagnosis and treatment?
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
What are the antigens associated with Rheumatoid arthritis, its pathology, diagnosis and treatment?
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
What are the antigens associated with contact dermatitis, its pathology, diagnosis and treatment?
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
What are the antigens associated with mantoux tests and its pathology?
Ag: - tuberculin Path: - Skin induration indicates TB exposure
71
What is the pathology of Crohn's disease, its diagnosis and treatment?
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
What are some features of CREST syndrome (limited cutaneous scleroderma) + its Abs for Dx?
- 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
What are some features of diffuse cutaneous scleroderma + its Abs for Dx?
- CREST + GIT + Interstitial pulmonary disease + renal problems - F:M = 4:1 Anti-topoisomerase/Scl70, RNA pol 1, 2, 3, fibrillarin Abs
74
What are some features of Sjogren's Syndrome + its Abs for Dx?
- 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
What are some features of IPEX syndrome?
- 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
What are some features of Coeliac Disease + its Abs for Dx?
- 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
What are the autoantibodies associated with APLS?
- Anti-cardiolipin - Anti-β2 glycoprotein - lupus anticoagulant
78
What are the autoantibodies associated with autoimmune hepatitis?
- Anti-smooth muscle antibody - Anti Liver Kidney Microsomal-1 - Anti-soluble liver antigen
79
What are the autoantibodies associated with AIHA?
- Anti- Rh Blood Group Antigen
80
What are the autoantibodies associated with AITP?
- Anti-glycoprotein IIb-IIIa Ab - Anti-glycoprotein Ib-IX Ab
81
What are the autoantibodies associated with Churg-Strauss Syndrome?
- perinuclear/protoplasmic-staining antineutrophil cytoplasmic antibody (p-ANCA)
82
What are the autoantibodies associated with coeliac disease?
- Anti-tissue tranglutaminase Ab (IgA) - Anti-endomysial antibody (IgA)
83
What are the autoantibodies associated with congenital heart block in infants of mothers with SLE?
- Anti-Ro Ab
84
What are the autoantibodies associated with dermatitis herpetiformis?
- Anti-endomysial Ab (IgA)
85
What are the autoantibodies associated with Dermatomyositis?
- Anti-Jo-1 (t-RNA synthetase)
86
What are the autoantibodies associated with Diffuse cutaneous scleroderma?
- Abs to topoisomerase/Scl70 - Abs to RNA pol I, II, III - Abs to Fibrillarin (nuclear pattern)
87
What are the autoantibodies associated with Goodpasture's syndrome?
- Anti-GBM Ab - TYPE IV COLLAGEN
88
What are the autoantibodies associated with Graves' Disease?
- Anti-TSH receptor Ab
89
What are the autoantibodies associated with Hashimoto's thyroiditis?
- Abs to thyroglobulin - Abs to thyroperoxidase
90
What are the autoantibodies associated with CREST syndrome (limited cutaneous scleroderma)?
- Anti-centromere Ab
91
What are the autoantibodies associated with Microscopic Polyangiitis (MPA)?
- Perinuclear/protoplasmic-staining antineutrophil cytoplasmic Abs (p-ANCA)
92
What are the autoantibodies associated with Mixed Connective Tissue Disease?
- Anti-U1RNP Ab (speckled pattern)
93
What are the autoantibodies associated with Myasthenia Gravis?
- Anti-ACh-receptor Ab - Anti-MUSK - Anti-VGCC (Lambert-Eaton)
94
What are the autoantibodies associated with Pernicious Anaemia?
- Ab to gastric parietal cells - Abs to Intrinsic Factor
95
What are the autoantibodies associated with Polymyositis?
- Anti-Jo-1 (t-RNA synthetase)
96
What are the autoantibodies associated with Primary biliary cirrhosis?
- Anti-mitochondrial Ab
97
What are the autoantibodies associated with Rheumatoid Arthritis?
- Anti-CCP - Anti-rheumatoid factor (less specific)
98
What are the autoantibodies associated with Sjogren's Syndrome?
- Anti-Ro Abs - Anti-La Abs (speckled pattern) - +ve RH
99
What are the autoantibodies associated with Sjogren's Syndrome?
- Anti-Ro Abs - Anti-La Abs (speckled pattern) - +ve RF
100
What are the autoantibodies associated with SLE?
- Abs to dsDNA - Abs to histones (homogenous) - Abs to Ro - Abs to La - Abs to SM - Abs to U1RNP (speckled)
101
What are the autoantibodies associated with T1DM?
- Abs to glutamte decarboxylase - Abs to pancreative β cells
102
What are the autoantibodies associated with Wegener's Granulomatosis?
- Cytoplasmic anti-neutrophil cytoplasmic Abs (c-ANCA)

Pathology (Guide) (84 decks)

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