T4 - L1 Allergic Diseases Flashcards
1
Q
what is an allergy/hypersensitivity?
A
an inappropriate immune response to:
- innocuous antigens
in a
- pre-sensitized (immune) host
2
Q
which types of hypersensitivity of antibody mediated?
A
types 1-3
3
Q
which types of hypersensitivity is cell mediated?
A
type 4
4
Q
what antibodies feature in a type 1 (anaphylactic) hypersensitivity reaction?
A
IgE
5
Q
what antibodies feature in a type 2 (cytotoxic) hypersensitivity reaction?
A
IgG
6
Q
what antibodies feature in a type 3 (immune complex) hypersensitivity reaction?
A
IgG
IgM
7
Q
what antibodies feature in a type 4 (delayed type) hypersensitivity reaction?
A
none
8
Q
what type of antigen features in a type 1 (anaphylactic) hypersensitivity reaction?
A
exogenous
9
Q
what type of antigen features in a type 2 (cytotoxic) hypersensitivity reaction?
A
cell surface
10
Q
what type of antigen features in a type 3 (immune complex) hypersensitivity reaction?
A
soluble
11
Q
what type of antigen features in a type 4 (delayed type) hypersensitivity reaction?
A
tissues and organs
12
Q
what the response time of a type 1 (anaphylactic) hypersensitivity reaction?
A
15-30 minutes
13
Q
what the response time of a type 2 (cytotoxic) hypersensitivity reaction?
A
minutes- hours
14
Q
what the response time of a type 3 (immune complex) hypersensitivity reaction?
A
3-8 hours
15
Q
what the response time of a type 4 (delayed type) hypersensitivity reaction?
A
48-72 hours
16
Q
IgG/IgM Ab response against combined self/foreign antigen at the cell surface is which type of hypersensitivity?
A
type 2 (cytotoxic)
17
Q
what are some clinical features of a type 2 (cytotoxic) hypersensitivity?
A
- onset: minutes to hours
- cell lysis and necrosis
18
Q
what is a common antigen of a type 2 (cytotoxic) hypersensitivity?
A
penicillin
19
Q
what are three associated diseases of of a type 2 (cytotoxic) hypersensitivity?
A
Erythroblastosis fetalis
Goodpasture’s nephritis
Penicillin Mediated Autoimmune Haemolytic Anaemia
20
Q
why type of sensitivity is referred to as cytotoxic?
A
type 2
21
Q
what is haemolysis?
A
the rupture or destruction of red blood cells.
22
Q
what is Erythroblastosis fetalis, and how does it occur?
A
- Hemolytic disease of the newborn
- mum is a different Rh blood type (e.g. mother is Rh- and newborn is Rh+)
- mum’s antibodies attack fatal blood resulting in haemolytic in unborn child/immediately after birth
23
Q
what are symptoms of Erythroblastosis fetalis seen in a newborn child?
A
- life-threatening anemia because of a lack of oxygen in the blood.
- jaundice
- fevered
- swelling
- enlarged liver and spleen.
24
Q
what is Goodpasture syndrome/Goodpasture’s nephritis?
A
antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure.
25
a disease associated with type 1 (anaphylactic) sensitivity?
allergic asthma
26
a disease associated with type 3 (immune complex) sensitivity?
SLE
27
a disease associated with type 4 (delayed type) sensitivity?
contact dermatitis
28
IgG/IgM Ab against soluble antigen would result in why type of hypersensitivity reaction?
type 3 – immune complex deposition
29
what are some clinical features of type 3 (immune complex) hypersensitivity?
- onset 3-8h
| - vasculitis
30
what is the traditional cause of a type 3 (immune complex) hypersensitivity?
serum sickness
NB: [Serum used to be used as a treatment for tetanus but immune system recognizes
the fluid and subsequently causes SLE]
31
what is SLE?
Systemic lupus erythematosus (SLE)
| - autoimmune disease
32
what are common symptoms of SLE?
- painful/swollen joints
- fever
- chest pain
- hair loss
- mouth ulcers
- swollen lymph nodes
- fatigue
- red rash most commonly on the face
33
Antigen specific T – cell mediated cytotoxicity is which type of hypersensitivity?
type 4 (delayed)
34
which type of hypersensitivity involves T cells?
type 4 (delayed)
35
what are some clinical features of a type 4 (delayed) hypersensitivity?
- onset: 48-72h typically
| - Erythema induration
36
how do we develop an allergy?
- combination of environment and genetic factors
- load od barrier function
- sensitisation of the immune system
- leading to IgE production
- These antibodies travel to cells that release chemicals, causing an allergic reaction
37
what would be an immune response to parasitic disease?
- increased levels of IgE
- tissue inflammation (Eosinophilia & Mastocytosis [mast cells], Basophil infiltration)
- CD4+ T cells secreting: IL4, IL5 & IL13
38
what type of cells are CD4+ T cells?
T helper cells
hey help the activity of other immune cells by releasing T cell cytokines.
39
what type of cells are CD8+ T cells?
Cytotoxic T cell
kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways.
40
what is the hygiene hypothesis?
lack of exposure to infectious agents and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system
41
can allergic immune responses be inherited?
no they are polygenic diseases
42
can allergic immune responses be inherited?
no they are polygenic diseases
43
which antibody is responsible for allergies?
IgE
44
which cytokines are responsible for allergy?
Cytokine gene cluster IL3,5,9,13
45
which cytokine receptors are responsible for allergy?
IL12R
IL4R
46
what is FcεR1?
- high-affinity IgE receptor
- Crosslinking of the FcεRI via IgE-antigen complexes leads to degranulation of mast cells or basophils and release of inflammatory mediators.
47
which cytokines work against allergies as part of the immune system?
IFNγ
TNF
48
what is an allergen?
an antigen that initiates an IgE-mediated response
49
describe a conventional immune response.
- allergen processed
- antigens presented to T-cells resulting in a cytokine release
- Results in delineation of T-helper subsets into different types [Th2 drives allergic conditions]
50
Genetic influences on the ‘allergic’ immune response are not sufficient for disease, ONLY susceptibility. What are the 4 groups of susceptibility genes for allergic disease?.
group 1: sensing the environment
group 2: barrier function
group 3: regulation of (atopic) inflammation
group 4: tissue response genes
51
the first encounter of an allergen doesn't always result in an IgE response, what does it result in instead?
First encounter results in innate & IgM response
52
how are IgE antibodies produced?
- An antigen (allergen) is recognized by both B-cell and Th2 cell
- Th2 can signal to B-cell (IL4) which can cause it switch to IgE proliferation
53
what is referred to as an "early priming event"?
- a breach in the initial barrier so allergen can access the immune system
- allergen taken up and antigens are presented by an antigen presenting cell (e.g. dendritic cell)
- stimulates T cells (in lymph node) and they differentiate into different T cell subtypes to initiate immune response
54
what is a Th2 cell?
a distinct lineage of CD4+ T helper cell that secretes:
IL-4, IL-5, IL-13
55
what are the 4 basic subtypes of CD4+ T cell?
Th1
Th2
Th17
Treg
56
what effector cytokines does Th1 secrete?
IFNy
| IL-2
57
what effector cytokines does Th2 secrete?
IL-4
IL-5
IL-13
58
what effector cytokines does Th17 secrete?
IL-17
IL-21
IL-22
59
what effector cytokines does Treg secrete?
IL-10
| TGFβ
60
which subtype of CD4+ T cell is the primary stimulator of a type 1 (anaphylactic) hypersensitivity reaction?
Th2
61
what is the role of the Th2 T cell?
- multiple cytokine release (IL-4 IL-5 IL-13)
- innate inflammatory response
- drive for IgE production
(activates innate and adaptive immune response)
62
describe the mechanism of a type 1 allergic response
- allergen detected by B and T cells
- T cells secrete IL-4 which help the B cells differentiate into plasma cells
- Plasma cell produces and secretes IgE
- IgE attaches to and pops mast cells - producing all the hypersensitivity reactions e.g.:
low blood pressure
smooth muscle contractions
vomting
mucous secretion
63
what stimulates mast cell and basophil degranulation?
IgE antibody
64
what happens during mast cell and basophil degranulation?
release of preformed and
| de novo synthesized inflammatory mediators
65
what are clinical features of a IgE mediated allergic response?
- fast onset: 15-30 min
| - wheal and flare
66
wheal and flare is a characteristic of which type of hypersensitivity?
type 1 (anaphylactic) hypersensitivity
67
what are the characteristic cells that mediates the late phase response in an IgE/type 1 allergic response?
mainly Eosinophils
Th2 T cells also contribute
68
during mast cell degranulation, what primary mediators (immediate/initial response) are released?
histamine
proteases
chemotactic factors (ECF and NCF)
69
during mast cell degranulation, what secondary mediators (delayed/late-phase response) are released?
Arachnoid acid metabolites including leukotrienes
| and prostaglandins
70
what are the effects of histamine?
- tachycardia
- blood clots
- gastric acide secretion (vomiting and diarrhoea)
- blood vessel dilation (hypotension)
- bronchoconstriction
- inc permeability of capillaries
- release of adrenaline
- swelling and inflammation
71
what is a protease?
an enzyme that helps proteolysis - protein catabolism by hydrolysis of peptide bonds
72
what are chemotactic factors?
substances that stimulates locomotion/cellular migration
e.g. chemokine, complement proteins 3a and 5a
73
what do leukotrienes do within an immune response?
trigger contractions in smooth muscles lining bronchioles
74
what do prostaglandins do within an immune response?
local acting vasodilation
aggregation of blood platelets
75
what conditions make up the atopic triad?
asthma
rhinitis
eczema
76
shat is the difference between asthma and rhinitis?
Asthma affects lower airway
Rhinitis affects upper airways
77
what are some symptoms of rhinitis?
Blocked nose, runny nose, sneezing and itchy nose - often with eye symptoms (Itching/burning, watery eyes, redness)
78
what is the treatment of rhinitis?
Antihistamines
| Nasal steroids
79
what are triggers of non-allergic rhinitis?
- vasomotor
- infection
- structural defects
- drugs
- hormonal treatment
- polyps
80
what is perennial allergic rhinitis?
you have it all year round
triggers such as dust mites, animals
81
what is seasonal allergic rhinitis?
you get it with change of season e.g. hay fever
82
a rhinitis triggered by dog fur is what type of rhinitis?
perennial
83
what is asthma?
INFLAMMATION & HYPER-REACTIVITY of small airways
84
immediate symptoms of asthma are mediated by which antibody?
IgE
85
due to asthma, the airways can become damaged, is this due to the initial or late phase response?
late phase response
NB: DAMAGED AIRWAYS ARE HYPER-REACTIVE to non-allergic stimuli e.g. fumes
86
which aero-allergic stimuli plays a key role in childhood asthma?
house dust mite
87
describe the pathogenesis of asthma?
- Allergens presented by APC to induce Th2 cells to secrete IL-4 to signal B-cells to make IgE Ab
- IgE bind to mast cell via FCER1 = mast cell degranulation
- release of histamine, leukotrienes, prostaglandins, cytokines, proteins and enzymes
= allergic response
88
what form of dermatitis is endogenous?
eczema
89
what form of dermatitis is exogenous?
contact dermatitis
NB: this is not due to immediate exposure, a delayed reaction
90
describe the pathogenesis of atopic dermatitis?
- barrier disruption
- allergen presented to T and B cells (T cells produce (IL-4 to stimulate B cell conversion into plasma cells = high IgE production)
- T cell also produces IL-31 responsible for itching which results in more barrier disruption = cycle continues
91
in atopic dermatitis which inflammatory cytokine is responsible for the itching sensation?
IL-31
92
what is filaggrin and what is it's role in the pathogenesis of atopic dermatitis?
Filaggrin binds to keratin fibres in epithelial cells to maintain epidermal homeostasis
Th2 Cells secrete IL-4/13 which inhibit the expression of Filaggrin leading to increased susceptibility of barrier disruption.
93
which inflammatory cytokines, secreted by TH2, inhibit the expression of Filaggrin increasing the epidermis' susceptibility to barrier disruption?
IL-4
| IL-13
94
with reference type 1 hypersensitivity, what is sensitisation?
induction of allergen
95
how does sensitisation occur?
- barrier disruption (allergen gains access to immune system)
- taken up by antigen-presenting cell (APC)
- APC travels to lymph nodes and presents antigens to naive T cells (Th0)
- T cells stimulated to secrete IL-4 to differentiate to Th2
- Th2 secretes IL-4 (positive feedback loop),5,13.
- IL-4 stimulates class switch in B cells to produce IgE Ab
- Mast cells have high affinity FCER1 receptor fir IgE that causes degranulation
96
which inflammatory cytokine stimulates the differentiation of a naive T cell (Th0) to a Th2 cell?
IL-4
97
which inflammatory cytokine stimulates the degranulation of eosinophils?
IL-5
98
which inflammatory cytokine stimulates the class switch of B cells?
IL-4
99
what is meant by "class switch" during sensitisation?
biological mechanism that changes a B cell's production of immunoglobulin from one type to another
e.g. IgM to IgE
100
Th2 plays central role in mediating delayed responses, what does it do?
- stimulates eosinophils, memory cells
- generates cytokines and chemokines
- drives mast cells and basophils
101
what tests can be done to diagnose an allergy?
- take history
- look for IgE in blood
- skin-prick test
- intra-dermal test
- graded challenge test (most reliable)
- basophil activation test
102
what does the intra-dermal test involved?
The test involves injection of a small amount of the suspected allergen under the surface of the skin. After about 20 minutes the area is examined for a reaction at the site.
NB: Can only use negative control here since histamine can cause damage.
103
what does the graded challenge test involve?
- Start with tiny amount of suspected allergens and then keep doubling the dose
- If the patient develops symptoms then stop it there and the diagnosis is found
- if no symptoms, then they are not allergic to that substance
104
what does the basophil activation test involve?
- take patients blood (which contains basophils)
- add allergen
- When have allergen and reassess basophils again, there are increased levels of these
markers: CD300a and CD203c
105
advantages of a IgE specific blood test when trying to diagnose an allergy?
safe
| - will not cause an allergic reaction.
106
advantages of a skin prick test when trying to diagnose an allergy?
- quick
| - patient satisfaction (they know what they're allergic to straight away)
107
disadvantages of a IgE specific blood test when trying to diagnose an allergy?
false negatives and false positives possible
108
disadvantages of a skin prick test test when trying to diagnose an allergy?
- false negatives and false positives possible
- risk of allergic reaction
- antihistamines can inhibit skin prick response
109
how do you treat a symptomatic allergy?
Antihistamines, Steroids, Adrenaline
immunosuppressive therapy if they don't respond to above treatments
