Hypersensitivity Reactions Flashcards
(155 cards)
1
Q
Hypersensitivity reaction
A
Exaggerated inappropriate immune reactions
2
Q
Type 1 hypersensitivity reaction
A
Interaction of antigen specific IgE and high affinity receptor for IgE on the mast cell surface results in cell degranulation
3
Q
Antigen in type I hypersensitivity reaction
A
Allergen
4
Q
The vasoactive mediators released in type I hypersensitivity give rise to what
A
Vasodilation and edema
5
Q
Skin in type I hypersensitivity reaction
A
Itchy, swelling and redness
6
Q
How fast from exposure to skin reaction in type I hypersensitivity
A
Minutes
7
Q
The antigens involved in type I hypersensitivity are usually __ molecules derived from the environment with no apparent threat to the host organism
A
Inert
8
Q
What else are type I hypersensitivity reactions called
A
Immediate hypersensitivity
9
Q
Prausnitz-kustner reaction
A
Serum was separated from the blood of kustner who was allergic to fish
Injected into prausnitz
Then inject fish into prausnitz and have a positive reaction
*the skin factor was called reagin
10
Q
Late hypersensitive immune reactions
A
Indirect result of mast cell degranulation as well as other mechanisms and have important pathogenic and therapeutic implications
11
Q
What are the allergic (type I hypersensitivity reactions)
A
Asthma Allergic rhinitis Urticaria Eczema Generalized anaphylaxis
12
Q
Several allergens have protease activity and it is possible that this is an important property for what
A
Crossing skin or mucosal barriers
13
Q
Features of allergens
A
In carrier particles (pollen grains) that are small and aerodynamic
Gives access to nasal and bronchial mucosa
14
Q
The tendency of allergic reactions has strong ___ and this tendency has been termed __
A
Heritability
Atrophy
15
Q
Atrophy
A
Presence of a type I hypersensitivity reaction to an allergen
16
Q
How is atropy determined
A
Skin prick test
17
Q
Risk of atropic disease when two, one or no parents have atropic trait
A
75, 50, 15
18
Q
What genes are involved in inheritance of atopy
A
B chain of high affinity receptor for IgE(FcERI-B)
IL4
CD14
HLA-DR
19
Q
What is the pathological hallmark of allergy
A
TH2 cells recognizing allergens , promoted by IL4
20
Q
Immune responsiveness for atopy
A
IFNy production decreases, more TH1
21
Q
Environment atopy
A
Hygiene hypothesis and early allergen exposure
22
Q
In monozygotic identical twins concordance for asthma is 20%. What does this mean
A
Environmental factors
23
Q
Cord blood of infants that are more likely to get atopy
A
High IgE low IFNy
24
Q
Hygiene hypothesis
A
Overzealous attention to cleanliness in developed societies has resulted in favor of TH1 like environment, has resulted in the favoring of th2 response
25
Early response asthma
Sensitive to antihistamines
Recover in 1-2 hours
Fall in FEV1
IgE mast cells
26
Early response hay fever
1-2 hours
Minutes have sneezing, increased secretions and nasal congestion
Sensitive to antihistamines
Mast cell IgE
27
Late phase response asthma
4-6 hours later
| Wheezing, hyperresponsiveness in the bronchi to challenge with allergen or histamine and reduced FEV
28
Hyperresponsiveness
Key clinical feature
29
Rhinitis late phase response
Nasal blockage and in skin allergy there is prolonged edema, swelling, and redness
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Are late phase responses responsive to antihistamines
No
31
What do you treat late phase responses
Corticosteroids
32
Early or late phase the most debilitating of hypersensitivity
Late
33
Cells of late response
Seen at six hours
Eosinophils 2-3 days
T cells 1-2 days
Neutrophils 6 hours
34
Eosinophils are recruited by what
Eotaxin il5
35
TH2 cell secretes what when see an allergen
Il4-b cell
GM-CSF, IL9, 3, 4, 5, 13, eotaxin for eosinophils
36
What do B cells secrete in type 1 hypersensitivity
IgE
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What does IgE bind to in type I
Mast cell
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What do mast cells secrete
PAF, LTB4, chemokines-for neutrophils
| Eosinophils attractants-for eosinophils
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What do th2 cells secrete that attract eosinophils
Eotaxin, il3, 4, 5, 13, GMCSF
40
What are the mediators of type I
Eosinophils early
| Neutrophils late
41
ELISPOT assay-detects T cell response
1.peripheral blood cells(lymphocytes, monocytes) mixed with soluble antigens
2. Culture this for 2 days
3. TH2 cell secreting IL4 in response to soluble antigen test
4. Remove cells and put onto antibody plate for il4
Il4 is captured by antibody
5. Cytokine is revealed by secondary antibody
5. Chemical reaction gives spots on dish.
IF SEE SPOTS POSITIVE IS NONE NEGATIVE
To see if allergy
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Cytokines of IgE production
IL4, 9, 13
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Mast cell cytokines
IL3, 4, 9
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Eosinophils development cytokines
IL3, 5, 9
45
Diagnose type 1 hypersensitivity
History
Skin prick
Blood eosinophil
46
Treatment of type 1 hypersensitivity
Avoidance and drugs , desensitization
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__ is the most common chronic disease of childhood affecting 5% of kids and 2% of adults
Asthma
48
What is asthma
Clinical syndrome of increased responsiveness of the bronchi to a variety of stimuli, with resultant airway narrowing, which reverses spontaneously or after drug therapy and is associated with cellular inflammation
49
Commonest allergensof asthma
House dust mites -dermatophagoides pteryonyssinus and d farinae (coat and fecal matter)
Grade pollen
50
What causes hyperresponsiveness
Prolonged damage to and inflammation of the respiratory epithelium
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How does hyperresponsiveness manifest
Bronchioconstriction, inflammation and mucus production with airway plugging in response to innocuous triggers that include upper respiratory tract infections, exercise , cold air, smoke and paint fumes
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Diagnose asthma
```
History
Cough, wheeze, SOB
FEV1
Bronchial hyperresponsiveness
Skin prick test
Serum IgE levels
```
53
How do we test hyperresponsiveness
Histamine or methacholine to produce a fall in FEV1
54
Therapy for asthma
NOT ANTIHISTAMINES
Education
Inhaled short acting B2 adrenoceptor agonist (salbutamol) which relaxes bronchial smooth muscle
55
Severe asthma treat
Inhaled B2 agonist and corticosteroid
56
What can corticosteroids do
Suppress production of prostaglandin and leukotreines mediators is suppressed, inflammatory cell recruitment and migration inhibited, vasoconstriction leads to reduced cell and fluid leakage from the vasculature
57
Administration of cysteinyl leukotrienes
Reproduce asthma symptoms
58
Allergic rhinitis
Common
| Hay fever
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Symptoms of allergic rhinitis/hay fever
Nasal congestion, sneezing, often in paroxysms, itching and nasal and post nasal discharge
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Allergic conjunctivitis
Frequently associated with allergic rhinitis
| Itchy, gritty, excessive eye watering
61
Hyperresponsiveness in rhinitis
Smoke and paint fumes trigger
62
Why may have hearing loss with allergic rhinitis
Fluid
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Diagnosis of allergic rhinitis
History
July June for grass and pollen , July august for mounds such as alternaria
Skin test mouth breathing, pale, blue edematous nasal turbinates, red line across the bridge of the nose caused by tendency to push the itchy nose upwards
Clear fluid in middle ear , serum IgE
64
Treat allergic rhinitis
```
Avoid
Antihistamines(prophalactively)
Nasal administer sodium cromoglicate (mast cell stabilizer) steroids,
CysLT1blockade(can also give for asthma)
Topical steroids
Desensitization
```
65
Desensitization
Allergen immunotherapy
Allergy can be prophylatically inoculated against
Give course of subcutaneous injections of increasing doses of allergen extract
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IgG blocking antibodies from desensitization
During repeated exposure to desensitizing allergen, IgG class antibodies develop; these compete with the pathogenic IgG for allergen binding (especially IgG4) and/or prevention IgE allergen complexes blinding to mast cell high affinity IgE receptors
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Regulation changes of desensitization
Exposure to repeated desensitization allergen induces Treg cells which recognize allergen but invoke regulatory immune responses, dampening down migration, infiltration and inflammation
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Immune deviation change in desensitization
A shift away from TH2 to TH1 producing CD4 cells results in the generation of cytokines which inhibitory to IgE
69
Atopic eczema
Dermatitis
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Hallmark of atopic eczema
Spongiosis
| Accumulation of edema fluid within and between keratinocytes in the epidermis, giving a spongy appearance
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Symptoms of atopic eczema
Itching, dry red patches with occasional vessels overtaken by crusting
Cheeks, abdomen and limb are involved in infancy
Elbow, knee, wrist flexor surfaces in children
Prolonged scratching leads to development of discolored plaques with a leathery texture (lichenification)
72
Diagnosis of. Atopic eczema
History
Skin test
IgE
73
Pathogenesis atopic excema
TH2
| IFNy
74
Urticaria
Hives or nettle rash
| Well circumcised itchy seals erupt over different areas of the body
75
What causes urticaria
Localized vasodilation and edema occurring in the superficial dermis
76
Angioedema
Edema forms deeper within the dermis giving larger areas of swollen tissue
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Why may angioedema arise in non allergic
Failure to inhibit complement cascade
78
Urticaria and angioedema may be caused by IgE mediated type I hypersensitivieies in which histamine is one of the dominant pathogenic mediators
However in the majority of cases a cause for urticaria/angioedema I’d not found
79
Urticaria associated with type 1 hypersensitivity in kids
Foodstuff
| Eggs chocolate nuts berries insect stings drug reactions
80
Diagnosis urticaria and angioedema
History
| Skin test
81
Anaphylaxis
Serious allergic reaction in rapid onset and may cause death
82
Anaphylaxis IgE mediated
Yup, Igee, mast cells, basophils, specific antigen
83
Anaphylaxis requires ___ by the allergen, followed by reexposure
Priming
84
How provoke anaphylaxis
Allergen systemically absorbed
Nut, shellfish, dairy
Wasp, bees, yellow jackets, hornetsmedications, entisera(tetanus, diphtheria), dextran, latex, some antibiotics
85
Symptoms anaphylaxis
Urticaria, cardiovascular collapse, laryngeal edema, airway obstruction , respiratory arrest leading to death
86
Pathogenesis of anaphylaxis
Happens or molecules
Penicillin allergy-derivatives animal derived serum
Cephalosporins
87
Peptide immunotherapy
Administer allergen peptide to induce treg
88
Pathogenesis of anaphylaxis
Activation of mast cells as basophils with systemic release of some mediators
89
Initial symptoms of anaphylaxis
Tingling, warmth itchiness
90
Symptoms of anaphylaxis
Vasodilation edema, flush urticaria, angioedema, hypotension, bronchospasm, laryngeal edema, cardiac arrhythmia or infarction
Death in minutes
91
How treat anaphylaxis
Adrenalin given intramuscular
| To bronchodilator and vasoconstrict as well as inhibit mast cell
92
What else is give to people with anaphylaxis
Oxygen
B adrenoceptor agonist such as salbutamol or theophylline followed by histamine H1 receptor antagonist and corticosteroids once acute phase is under control
93
What causes prolonged hypotension after anaphylaxis
Vasodilation and fluid loss into tissue
94
Type II hypersensitivity reactions
Initiated by the interaction between antibody and antigen but in these cases IgE is ot involved
95
Target of antigen in type II
Fixed in tissue
96
Consequence of antibody binding to cell surface antigen in type II
Complement is activated leading to cell lysis, mast cell activation and neutrophil recruitment
The antigen antibody complex recruits cell directly through Fc interactions . The arrival of cells with cytotoxic capability may lead to ADCC. In addition, there may be function loss and change of cell receptors
97
Type II organ specific
Myasthenia gravis
Antiglomerular basement membrane glomerulonephrtis
Pemphigus vulgaris and bulbous pemphigus
98
Type II autoimmune cytopenias
Haemolytic Angelia
Thrombocytopenia
Neutropenia
99
Autoantibodies in type II
Stimulate through surface receptors to which they bind as happens in relation to autoantibodies that bind the thyroid stimulating hormone receptor in graces. Other autoantibodies block receptors-
100
Type II hypersensitivity
Antigen antibody complexes form int he circulation and become deposited int the tissue, or they may actually form within tissues
101
Arthur’s reaction
Type III inject
Antigen antibody complex forms
Erythematous lesion of 3-6 hours
102
Two forms of hypersensitivity reaction
Complexes form in circulation and deposit
| Form in tissues
103
Factors influencing immune complex formation and damage
Charge and persistence
Charged molecule such as dna is more likely to be atttracted to and become attached to charged areas within the body such as the glomerular basement membrane
Persistend production of antigen will lead to a continuous supply of complexes overloading the remora always process and amplifying the opportunities for deposition and damage
104
What antigen has persistence
Bacterial proteins continuously cast off of heart valves during infective endocarditis and similar proteins emanating from infected ventriculo-peritoneal shunts used to relieve high intracranial pressure
105
The host response is important in determining the potential pathogenicity of immune complexes. The isotype of an antibody in a complex influences complement fixations and thus its solubility.
The integrity of the complement cascade is also an important determinant of whether complexes are solubilized and removed.
106
Function of the classical pathway which requires C2 and C4, is critical in solubility antigen-antibody complexes
Genetically determined defiency of complement component C4 is found in approximately half of patients with SLE, one of the best examples of a disease in which immune complexes contribute to pathogenesis
107
C2 defiency is much rarer, but almost all patients with this defect have an SLE like syndrome
Patients with SLE also have defective complement receptor expression on their red blood cell surface, further reducing their buffering capacity for immune complexes
108
The tissues typically exposed to injury by immune complexes are the renal glomerulus and the joint synovial.
These are tissues in which plasma from the blood is ultrafiltration to form urine and synovial fluid, respectively.
109
The hydrostatic pressure involved in such a process and the filtrate function of the glomerular basement membrane are likely to contribute to the retention and therefore, the pathogenicity of immune complexes
Ok
110
=relative proportions of antigen and antibody
Complexes formed in antigen or antibody excess are less likely to deposit
111
Impaired classical complement pathway function
Classical pathway has key role in solubizing and transporting complexes
112
Isotype of antibody
Isotype dictates ability to fix complement
113
Rate of complex formation
If the rate of formation excesses clearance , complex deposition is enhanced
114
The variety of factors capable of influencing immune complex deposition is paralleled by the variety of diseases that are known to be immune complex mediated
There are three broad categories of immune complex disease
115
In some,t he immune complexes formed int he circulation deposit in the tissues, leading directl to nephritis, synovitis or irities
In a second group, complex deposition is predominantly into the walls of medium or small sized arterioles and the vsacultitis that ensures is the cause or organ damage in the kidney, skin or other organs
116
In others, particularly the type II lung disease, antigens and antibody combine within the tissue, removing an __ ___
Arthur’s reaction
117
Deposited formed in tissue
Group a strep, DNA, bacterial antigens
118
Group a strep
Post strep nephritis
| Nephritis
119
DNA
SLE
| Nephritis serositis
120
Bacterial antigens
SBE, shunt nephritis
| Nephritis
121
Vessel deposition
HBsAg, DNA, bacterial antigens
122
HBsAg
Polyarteritis nodosa
| Vasculitis
123
DNA
SLE
| Vasculitis
124
Bacterial antigens
SBE
| Vasculitis
125
Forms in tissue
Various microbial and chemical antigens
126
Various microbial and chemical antigens
EAA
| Pneumonitis
127
Extrinsic allergic alveolitis
Hypersensitivity pneumonitis , outcome of occupation and pastime related diseases
128
What causes EAA
Overexposure over many months or years to excessive amounts of inhaled antigen leads to the generation of large concentrations of antibodies within the lung interstitium
129
At a subsequent exposure, immune complex formation takes place on a massive scale in the alveoli
Typically, patients present 3-6 hours after loading mouldy hay, cleaning the pigeon loft or packing the sugar cane with symptoms of fever chills malaise and dyspnoea
130
They may admit to milder episodes leading up tp the presenting illness
Symptoms usually remit within 24 hours but chronic exposure can lead to progressive SOB with cyanosis lung fibrosis and the development of cor pulmonary
131
The diagnosis is made on the history and the demonstration of circulating IgG antibodies (called precipitins) to the provoking antigen
Farmers lung has declined in recent years with changes in farming practice but bird related pastimes remain popular hence bird fanciers disease is the commonest EAA
132
Bird fanciers disease
Various avian antigens (pigeons, cockatoos, parakeets, budgerigars)
133
Farmers lung
Fungal antigens in moldy hay
134
Baggassosis (sugar cane workers disease
Thermoactinomyces sacchari antigen
135
Paprika slicers lung
Mucor stolonifer is antigen
136
The antigens involved are usually associated with small particles that promote transportation to the alveolar space
Although pathogenesis of the disease is classically type II there is probably a cell mediated component with the documented formation of granulomata
137
It is not clear why some individuals develop disease whilst other do not , although HLA association have been described
Management is composed of exposure avoidance strategies and oral corticosteroids
138
Type IV
Certain inflammatory conditions associated with tissue damage are characterized by cellular infiltrates, appearing 24 hours after challenge and composed int he main of a combination of lymphocytes and macrophages
139
If antigen persists, inflammation becomes chronic and the macrophages in the lesion fuse to form giant cells and epithelium cells
What else are type IV called
140
Delayed type hypersensitivity
Include reactions to mycobacteria and other organisms which the immune system has difficulty eliminating
141
Reactions range from the local redness and swelling seen at the site of intradermal tests for Tb immunity in which an extract fromt he organism is injected to the caseating necrosis that occasionally results from hosts attempts to deal with mycobacterium TB
Granulomata which wall off the infective focus may also arise in response to other infections , such as parasitic worm infecstation of schistosomiasis
142
Within the granulomata, there is extensive tissue damage, with fibrosis and calcification
This type of reaction can have serious clinical consequences if the site of damage is the lung, liver or bone
143
If these circumstances, the immune system is caught between the repercussions of not dealing with the infection and the tissue damage that is caused by activated and differentiated macrophages
Dc and macrophages are activated by TH1 lymphocytes and release powerful hydrolytic enzymes and toxic oxygen metabolistes
144
Other factors released within the infiltrate encourage fibrosis and angiogenesis
Another example of IV is that resulting in some individuals from exposure to contact with nickel jewelry , dichromate int he leather industry of p-phenyldiamine in sunscreen or hair dyes
145
This reaction is confined to the skin and called ___ ___
Contact dermatitis
146
Contact dermatitis
There is an eczematous reaction with erythema, edema, vesicles, and scaling
147
How long does contact dermatitis to appear
48 hours
148
Patch testing
Potential contact sensitized are placed in contact with the skin on the back for 48 hours
149
Hapten
Substances incapable bc of small size to provoke antibodies without conjugation to carrier proteins
-contact dermatitis
150
Metals of compounds in sensitizing agent becomes conjugated to tissue proteins
Contact dermatitis
| Haptens
151
How recreate type IV in vitro
Lymphocytes froma. Reactive individual are cultured with the provoking agent
Measurement of T cell proliferation or release of cytokines such as iFn y are a useful assessment of the degree of reactivity and of relevance to the pathogenic processes
152
Antibody recruiting complement and cytotoxic cells with Fc receptors can cause tissue damage.
This is frequently an autoantibodies. The antigenic targets may be tissue fixed (typeII ) or incirculation (typeIII0
153
In type II the target cell surface antigens may be altered self or exogenous cells
In type III the immune complex may be deposited in tissue of vessels (SLE) or may form in tissues (farmers lung)
154
Hypersensitivity resulting from T cell reactions is usually delayed in onset
The central cells in their type IV hypersensitivity are the CD4 and the macrophages
155
Granulomata are characteristic and contact dermatitis is a typical clinical example
Ok
