Hypersensitivity Reactions Flashcards
Types of hypersensitivity
Type 1: immediate hypersensitivity
Type 2: cytotoxic hypersensitivity
Type 3: serum sickness and Arthus reaction
Type 4: delayed-type hypersensitivity, contact dermatitis
Hypersensitivity - define
An inappropriate immune response to non-infectious antigens that results in tissue damage and disease
Systemic anaphylaxis - define
Systemic anaphylaxis is a life-threatening allergic event resulting in massive, generalized mast cell degranulation.
Type II hypersensitivity reactions respond to
Type II hypersensitivity reactions respond to altered components of human cells
Antibody-bound cells are cleared by:
Antibody-bound cells are cleared by:
FcγR+ cells such as macrophages
complement
Special case of a Type II response:
Special case of a Type II response:
involves IgG antibodies directed at cell-surface receptors
these antibodies disrupt the normal functions of the receptor by either:
uncontrollable activation or blocking receptor function
Examples of Type 2 HS
Grave’s disease
Myasthenia gravis
Hemolytic disease of the newborn
Myasthenia gravis - define
Antibodies block or destroy nicotinic acetylcholine receptors at the junction between the nerve and muscle
Grave’s disease - define
Graves’ disease is an autoimmune disorder that causes hyperthyroidism, or overactive thyroid.
Immune system attacks the thyroid = more TH made than needed
Hemolytic disease of the newborn - defomne
A blood problem in newborn babies. It occurs when your baby’s red blood cells break down at a fast rate
Type III - describe effector mechanism
IgG and soluble antigen form immune complexes
Immune complexes are cleared by phagocytes.
Describe events leading to occlusion of small BVs
activate mast cells to release inflammatory mediators.
inflammatory cells invade the site, and blood vessel permeability and blood flow are increased.
Platelets also accumulate, leading to occlusion of the small blood vessels, hemorrhage, and the appearance of purpura.
Serum sickness - cause
caused by large intravenous doses of soluble antigens (e.g. drugs)
Serum sickness - explain the tissue damage
IgG antibodies produced form small immune complexes with the antigen in excess.
immune complexes deposited in tissues e.g. blood vessel walls.
tissue damage is caused by complement activation and the subsequent inflammatory responses
What determines the pathology observed in type III hypersensitivity reactions
Antigen dose and route of delivery determine the pathology observed in type III hypersensitivity reactions
Time course of delayed (Type IV) hypersensitivity - describe
Antigen injected into subcutaneous tissue and processed by local antigen-presenting cells
A TH1 effector cell recognizes antigen and releases cytokines that act on vascular endothelium
Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion
Mantoux test - desribe
The Mantoux test is a widely used test for latent TB.
It involves injecting a small amount of a substance called PPD tuberculin into the skin of your forearm. It’s also called the tuberculin skin test (TST).
Tuberculoid leprosy - describe
Type 4
Tuberculoid leprosy is a form of leprosy characterized by solitary skin lesions that are asymmetrically distributed with few lesions and well demarcated edges. There is also early and marked nerve damage.
Contact dermatitis - describe
Type 4
Contact dermatitis is a red, itchy rash caused by direct contact with a substance or an allergic reaction to it.
Poison ivy - describe
Poison ivy rash is a type of allergic contact dermatitis caused by an oily resin called urushiol.
This resin is very sticky, so it easily attaches to your skin, clothing, tools, equipment and pet’s fur.
Type I : Allergy - define
defined as “disease following a response by the immune system to an otherwise innocuous antigen”
What is IgE?
First line of defence against worms
Binds FcεR1 receptor on mast cells
Pre-arms mast cells to react when in the presence of antigen
Allergen-specific IgE Production:
The simple Model = describe
First exposure to pollen
IL-4 drives B cells to produce IgE in response to pollen antigens
Pollen-specific IgE binds to mast cell
Second exposure to pollen
=
acute release of mast-cell contents causes allergic rhinitis (hay fever)
What causes Allergic Sensitisation?
What causes Allergic Sensitisation?
Exposure to Allergen is critical, this includes: Nature of the allergen Dosage of Allergen (high vs. low) Timing Location of Priming
Role of pro-allergic dendritic cells and cytokines
Genetic predisposition to Allergy
Describe naming of allergens
Allergens are named systematically:
After the source organism and the order they were discovered
e.g. Der p1 comes from Dermatophagoides pteronyssinus
Not all proteins are allergenic
Filaggrin and Atopic Dermatitis - describe relation to one another
Filaggrin links skin integrity and allergy
When it is defective atopic dermatitis is greater
This is due to the access for allergens
What Makes Dendritic Cell Pro-Allergic?
Not Known
but
One Candidate Protein is TSLP
This may switch DC to a ‘pro-allergic’ state
(TSLP= Thymic stromal lymphopoietin)
Describe mast cell activation
Resting mast cell contains granules containing histamine and other inflammatory mediators
Bound IgE is
allergen-specific
Specific allergen
crosslinks IgE =
Multivalent antigen cross-links bound IgE antibody, causing release of granule contents
Early and late phase allergic response - describe its mediators
Allergic responses have an early and late phase
Early is mediated by mast cells
Late is mediated by T cells
Acute Allergic
Reaction - describe
Acute Allergic
Reaction
Wheezing
Urticaria
Sneezing,rhinorrhea
Conjunctivitis
Chronic Allergic
Reaction - describe
Chronic Allergic
Reaction
Further wheezing
Sustained blockage
of the nose
Eczema
Histamine - function
Effector mediator produced by mast cells:
increase vascular permeability
cause smooth muscle contraction
Leukotrienes - function
Effector mediator produced by mast cells:
increase vascular permeability
cause smooth muscle contraction
stimulates mucus secretion
Prostaglandins - function
Effector mediator produced by mast cells:
chemoattractants for T cells,
eosinophils and basophils
Il-4 + IL-13 - function
Effector mediator produced by mast cells:
promotes Th2
promotes IgE
TNF-α - function
Effector mediator produced by mast cells:
promotes tissue inflammation
Mast cell activation - effect on GI tract
Increases fluid secretion + peristalsis
=
Expulsion of GI contents (diarrhea, vomiting)
Mast cell activation - effect on airways
Decreased diameter, increased mucus secretion
=
Congestion/blockage (wheezing, coughing, phlegm)
Swelling/mucus secretion in nasal passages
Mast cell activation - effect on BVs
Increased BF, increased permeability
=
Increased fluid in tissues = increased flow of lymph to lymph nodes
Increased cells/protein in tissues
Increased effector response in tissues
Eosinophils - location + why are they recruited
Eosinophils:
located in the tissues
recruited to the sites of allergic reactions
express FcεRI upon activation
The two effector functions of eosinophils:
The two effector functions of eosinophils:
- Release highly toxic granule proteins and free radicals upon activation to kill microorganisms/parasites and cause tissue damage in allergic reactions.
- Synthesise and release prostaglandins, leukotrienes and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes.
The late phase of the IgE-mediated allergic response - characteristics
Late-phase reaction is dependent on allergen dose
Continued synthesis and release of inflammatory mediators
Chronic allergic inflammation caused by Th2 cells i.e. a type IV hypersensitivity reaction
The late phase of allergic response - explain the potentiation of further responses
The late phase of allergic response is T cell mediated:
Mostly consisting of allergen specific Th2 cells
These cells recruit other cells by cytokine release
Potentiate further responses
Explain how an allergy develops by comparing sensitisation/reaction
There is a key difference between sensitisation to allergen and reaction to allergen.
Individuals must be sensitised to an allergen before they can react.
Sensitisation requires presentation of allergen to T cells by DC and the priming of Cognate B cells to produce IgE
The Reaction to allergen occurs when the individual is re-exposed to allergen and it binds preformed IgE on mast cells
Asthma - define
“A State of reversible bronchial hyper-reactivity resulting from a persistent inflammatory process in response to a number of stimuli in a genetically susceptible individual”.
Non-atopic asthma includes what
Non Atopic includes:
Occupational
Exercise induced
Nocturnal Asthma
Post-bronchiolitic Wheeze
Allergic Asthma - characteristics
Characteristics:
episodes of wheezy breathing
narrowing of the airways
rapid changes in airway
obstruction
severity varies
- slight wheeziness to asthma
attack
common allergens causing
asthma include
pollen
HDM
plants
some foods
Allergic Asthma - describe acute response
Acute response:
occurs within seconds of allergen exposure
results in airway obstruction and breathing difficulties
caused by allergen-induced mast cell degranulation in the
submucosa of the airways
Allergic Asthma - describe chronic response
Chronic response:
chronic inflammation of the
airways
caused by activation of
eosinophils, neutrophils,
T cells and other leukocytes
mediators released by these cells cause airway remodelling, permanent narrowing of the airways, and further tissue damage
Blockage of effector pathways: - describe
Blockage of effector pathways:
inhibit effects of mediators on specific receptors
anti-histamine (block the histamine H1 receptor)
inhibit mast cell degranulation
mast cell stabilizer (e.g. chromoglycate)
inhibit synthesis of specific mediators lipoxygenase inhibitors (e.g montelukast)
How can you inhibit effects of mediators on specific receptors
inhibit effects of mediators on specific receptors
- anti-histamine (block the histamine H1 receptor)
How can you inhibit mast cell degranulation
inhibit mast cell degranulation
mast cell stabilizer (e.g. chromoglycate)
How can you inhibit synthesis of specific mediators
inhibit synthesis of specific mediators lipoxygenase inhibitors (e.g montelukast)
Describe use of steroids in allergies
Steroids – Act directly on DNA to increase transcription of anti-inflammatory mediators (e.g. IL-10) and decrease transcription of pro-inflammatory mediators (e.g prednisolone)
Describe use of bronchodilators in allergies
Bronchodilators – Reverse acute effect of allergy on airways (e.g B2 agonist salbutamol)
Describe use of immunotherapy in allergies
Immunotherapy – Reverses the sensitisation to allergen by means of tolerising exposure
Describe 2 important phases of allergies
2 important phases:
Sensitisation – allergen presented by DC to Th2 CD4 T cells and B cells
Reaction – IgE on mast cells cross-linked by cognate antigen leading to inflammation
