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Year 2 Clinical Pathology > Allergy > Flashcards

Allergy Flashcards

1
Q

What is meant by allergic and hypersensitive reactions?

A

Undesirable, damaging and sometimes fatal reactions produced by the normal immune system - key factor is its directed against an innocuous antigens in a pre-sensitized host

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2
Q

Which hypersensitivity reactions are Ab mediated and which are cell mediated?

A

Types 1-3 = Ab mediated

Type 4 = Cell mediated

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3
Q

Type 3 hypersensitivity reactions are also referred to as what?

A

Immune complex reactions

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4
Q

Type 2 hypersensitivity reactions are also referred to as what?

A

Cytotoxic reactions

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5
Q

Type 4 hypersensitivity reactions are also referred to as what?

A

Delayed type

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6
Q

Which type of hypersensitivity reaction is the classic allergic reaction?

A

Type 1

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7
Q

Type 1 hypersensitivity reactions are mediated by which type of Ab?

A

IgE

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8
Q

Types 2 and 3 hypersensitivity reactions are mediated which types of Ab?

A

IgG and IgM

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9
Q

What is the immunopathogenesis of a Type 2 Hypersensitivity reaction?

A

1) IgM/IgG Ab response against combined self/foreign Ag at the cell surface
2) When Ab binds to Ag on solid surface get complement activation and activation of phagocytic cells, ADCC (Ab dependent cellular cytotoxicity)

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10
Q

What are the clinical features of Type 2 cytotoxic reactions?

A

1) Onset is minutes to hours

2) Cell lysis and necrosis

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11
Q

What is a common antigen causing a Type 2 cytotoxic reaction?

A

Penicillin

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12
Q

Give 2 diseases associated with Type 2 cytotoxic reactions?

A

1) Eryhtroblastosis fetalis (Rhesus reaction)

2) Goodpasture’s nephritis

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13
Q

What roughly happens in the rhesus reaction?

A

Rhesus negative mother - exposed to Rh+ child on first pregnancy and develops antigens - sensitisation
On second pregnancy with Rh+ baby - Abs bind to Ag and get cell lysis

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14
Q

What is the immunopathology of Type 3 hypersensitivity reaction?

A

IgG/IgM Ab against soluble antigens - immune complex deposition

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15
Q

What are the clinical features of a Type 3 hypersensitivity reaction?

A

1) Onset 3-8 hours

2) Vasculitis

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16
Q

Type 3 hypersensitivity reactions are the traditional cause of what?

A

Serum-sickness

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17
Q

Which disease is associated with Type 3 hypersensitivity reaction?

A

SLE

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18
Q

When the route of entry of antigen is intravenous in a type 3 hypersensitivity reaction what are the 3 resulting diseases and 3 sites of immune complex deposition?

A 
Diseases
1) Vasculitis
2) Nephritis
3) Arthritis
Site of deposition
1) Blood vessel walls
2) Renal glomeruli
3) Joint spaces
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19
Q

When the route of entry of antigen is subcutaneous in a type 3 hypersensitivity reaction what is the resulting disease and site of immune complex deposition?

A

Disease - Arthus reaction

Site - Perivascular area

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20
Q

When the route of entry of antigen is inhaled in a type 3 hypersensitivity reaction what is the resulting disease and side of immune complex deposition?

A

Disease - Farmer’s lung

Site - Alveolar/Capillary interface

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21
Q

What is the key difference between a Type 2 and 3 hypersensitivity reaction?

A

Type 2 - Ab against Ag attached to a cell surface so cell lysis
Type 3 - Ab against soluble Ag so immune complex deposition

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22
Q

What is the immunopathology of Type 4 (delayed type) hypersensitivity reaction?

A
  • Ag specific T-cell mediated cytotoxicity
    Exposure to Ag, develop T cell which can recognise that Ag
    On re-exposure T cells cause tissue damage by release of various mediators
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23
Q

What are the clinical features of a Type 4 hypersensitivity reaction?

A

1) Delayed onset

2) Erythema induration

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24
Q

Give 1 common Ag in a type hypersensitivity reaction?

A

Metals eg. nickel

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25
The tuberculin reaction is an example of what kind of hypersensitivity reaction?
Type 4
26
Give a disease associated with Type 4 hypersensitivity?
Contact dermatitis
27
What are the 5 key steps in the development of allergy (Type 1 hypersensitivity)?
1) Barrier dysfunction - allowing entry of Ag 2) Sensitisation 3) Changes in T cell sub-sets dominated by Th2 4) IgE Ab produced 5) Allergic symptoms
28
Which 6 organs are commonly involved in allergic reactions?
1) Eyes - allergic conjunctivitis 2) Nose - allergic rhinitis 3) Mouth - oral allergy syndrome 4) Airways - allergic asthma 5) Skin - atopic dermatitis 6) GI tract - food allergy
29
What is the link between parasitic infection and allergies?
Those components of the immune system involved in responses to parasitic infection are also involved in allergic responses The system has developed to produce a rapid tissue-based response to re-infection
30
What are the main 3 components of immune response to parasitic disease?
1) Increased levels of IgE - total and specific to pathogen 2) Tissue inflammation with eosinophilia and mastocytosis and basophil infiltration 3) Presence of CD4+ cells secreting IL4,IL5 and IL13
31
What is the general principle of the 'hygiene hypothesis' in relation to increased allergies?
Infections seem to have some affect on developing atopic conditions and autoimmune disorders in animal models Th1 response is thought to be towards management of infections, Th2 response directs towards allergies Simplistic theory is that if you don't have the competition from infectious agents, allergens and the Th2 response predominate - in line with the Th2 deviation seen in atopic conditions
32
What is the genetic influence of the allergic immune response?
Polygenic disease Genetic factors alone are not sufficient for the disease, only increase susceptibility Need the environmental factors
33
What 5 areas can you have genetic defects in leading to increased susceptibility to allergic disease?
1) Environment sensing - ie being hypersensitive 2) Atopic immune response 3) Defects in barrier function so allergens can get in 4) Tissue response - may have an inappropriate response 5) Eosinophils
34
Has asthma, atopic dermatitis or rhinitis been show to be associated with more genetic defects?
Atopic dermatitis is associated with the most defects followed by asthma, followed by rhinitis
35
What is meant by allergens?
Antigens that initiate an IgE mediated response
36
What is key in hypersensitive reactions in terms of exposure to Ag?
Can only have a hypersensitive reaction on re-exposure to an allergen to which you have previously been exposed ie. sensitised
37
In allergic reactions what response does the first encounter with an allergen result in?
Innate and IgM response
38
What is the immune process in an IgE allergic response (Type 1 hypersensitivity)?
1) Exposure to Ag which is presented to T cells by APCs 2) T cell cytokine release resulting in Th2 delineation and B cell activation to produce IgE 3) IgE Fc portion binds to mast cell IgE receptors 4) On re-exposure allergen binds to Fac portion of mast cell bound IgE 5) Cross linking causes release of mediators from mast cells and basophils leading to symptoms
39
What 6 cells/organs are affected by the pre-formed mediators released by mast cells/basophils in an allergic reaction?
1) Smooth muscle 2) Blood vessels 3) Platelets 4) Mucous glands 5) Sensory nerve endings 6) Eosinophils
40
T cells can differentiate into what 4 types - what does each roughly do?
1) Th1 - fights infections 2) Th2 - allergic reactions 3) Th17 - fights infection 4) Treg - suppresses all other types
41
Which cytokine released by Th2 cells is important in leading to the production of IgE by B cells?
IL-4
42
What 3 steps are considered to be the early priming events in allergic reactions?
1) Defect in epithelial barrier 2) Allergen taken up actively or passively 3) Allergens processed by APCs and activate T cells
43
What is the clinical features of IgE mediated allergic response?
1) Fast onset (15-30 mins) | 2) Wheal and flare
44
Which 2 types of cell are heavily involved in the late phase response of an allergic reaction?
1) Eosinophils | 2) Th2 cells
45
Which is the commonest pre-formed mediator released by mast cells causing the immediate response in allergic reactions?
Histamine
46
Secondary mediators playing a role in the late phase reaction of allergic response are produced by what pathway in the mast cell, what are the main 2?
Produced via the arachidonic acid pathway | Leukotrienes and prostaglandins are the main 2
47
What are the 3 main roles of Th2 T cells in allergic reactions?
1) Multiple cytokines released 2) Activates innate inflammatory response 3) Drives immunoglobulin production by B cells
48
What 3 conditions make up the atopic triad, what kind of hypersensitivity reaction is associated with each?
1) Asthma - Type 1 2) Rhinitis - Type 1 3) Eczema - Type 4
49
What is the main difference between immunopathology in rhinitis and asthma?
1) Rhinitis = type 1 reaction in nasal mucosa (upper airways) 2) Asthma = type 1 reaction in alveolar epithelium (lower airways)
50
What are the 2 types of rhinitis?
1) Allergic | 2) Non-allergic
51
What determines whether allergic rhinitis is perennial or seasonal?
When the allergens are present eg. Host mite - perennial Pollen - seasonal
52
What are the main 3 symptoms of rhinitis?
1) Blocked nose 2) Runny nose 3) Often eye symptoms
53
What are 3 common allergens causing rhinitis?
1) House mite 2) Animal danders 3) Pollens
54
What are the 2 main treatments of rhinitis?
1) Anti-histamines | 2) Nasal steroids
55
What are the common allergens in childhood asthma?
Aero-allergic stimuli | House dust mite thought to have a key role
56
Is damage to airways in asthma caused by the immediate or late phase response?
Late phase response
57
What is the main problem with damaged airways in asthma?
They are hyper-reactive to non-allergic stimuli eg. fumes
58
Immediate symptoms in asthma are mediated by what?
IgE Ab
59
Which 2 substances released by mast cells in the late phase reaction are key in asthma?
Leukotrienes and Prostaglandins
60
What are the 3 types of dermatitis?
1) Atopic - eczema 2) Allergic - type 4 hypersensitivity 3) Non-allergic
61
How does dermatitis of all types present clinically?
1) Intense itching 2) blistering/weeping 3) cracking of skin
62
What is thought to be a major trigger in atopic dermatitis?
House dust mite
63
What is the treatment of atopic dermatitis?
Topical steroids and moisturisers
64
What is the mechanism thought to be the reasons for itching in atopic dermatitis?
1) Activated T cells release a cytokine called IL31 - T cell itch mediator 2) Directly causes a scratch which leads to a cycle of barrier disruption and further exposure to hapten
65
What is anaphylaxis?
An acute, potentially life threatening IgE mediated systemic hypersensitivity reaction
66
What are the GI, respiratory, CV and neurological symptoms in severe anaphylaxis?
GI - Profuse diarrhoea, loss of bowel control Respiratory - Severe wheezing, cyanosis, resp. arrest CV - Hypotension, bradychardia, collapse, cardiac arrest Neurological - Confusion, loss of consciousness
67
What is the gold standard test in diagnosis of allergy?
Oral challenge test
68
What 7 tests/procedures can be used in the diagnosis of allergy?
1) History 2) Specific IgE 3) Skin prick test 4) Intra-dermal test 5) Oral challenge test 6) Basophil activation test 7) Component resolved diagnostics
69
What is the principle of the basophil activation test?
Mix patients blood with allergen | Upon cross linking basophils upregulate the expression of specific activation markers which can be detected
70
What is the 1 advantage and disadvantage of the specific IgE test over the skin prick test?
Ad - safe | Disad - false positives and negatives
71
What are the 2 advantages and disadvantages of the skin prick test over the specific IgE test?
Ad - quick and patient satisfaction (they have seen it themselves) Disad - false positives and negatives, slight risk
72
What are the 3 symptomatic treatments of allergic reactions?
1) Antihistamines 2) Steroids 3) Adrenaline
73
What are the 3 indications for specific immunotherapy (sublingual or subcutaneous) in allergy?
1) Life threatening reactions to wasp and bee sting 2) Severe hay fever 3) Animal dander allergy
74
In which 3 situations is specific immunotherapy for allergy not useful?
1) Multiple allergies 2) Food allergies 3) Allergic rashes - eczema, urticarial
75
What is the main principle of immunotherapy for allergy?
Trick the immune system to tolerate the antigen through controlled exposure Switch from Th2 to Th1 response
76
What are the 6 major food allergens?
1) Cow's milk 2) Egg 3) Legumes (peanut, soybean, tree nuts) 4) Fish 5) Crustaceans/Molluscs 6) Cereal grains
77
What are the 4 common clinical manifestations of adverse reactions to food?
1) GI - vomiting diarrhoea, oral symptoms 2) Respiratory - rhinitis and bronchospasm 3) Cutaneous - urticarial, angioedema 4) Anaphylaxis
78
What are the 4 clinical manifestations of IgE mediated reactions to drugs?
1) Urticaria 2) Angioedema 3) Bronchospasm 4) Anaphylaxis

Year 2 Clinical Pathology (64 decks)

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