57. Hypersensitivity Reactions Flashcards
The four 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
Type 1: immediate hypersensitivity
- Induce allergy by injecting allergen into the skin or by scratching it on the surface of the skin
- You get a wheal and flare formation ~ shows you are allergic
- How you would do allergy testing
e.g. Allergic rhinitis
Asthma
Anaphylaxis
Type 2: cytotoxic hypersensitivity
- The attachment of the drug on the surface of the RBC makes it seem foreign
- These activate the macrophages and complement, causing inflammation
e.g. Some drug
allergies
i.e. penicillin
=> 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
Type 3: serum sickness and Arthus reaction
They already have the antibodies and the high levels of antigen locally causing localized immune complexes and so localized inflammation and localized immune response
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.
e.g. Arthus reaction
Serum sickness
Type 4: delayed-type hypersensitivity, contact dermatitis
•2 forms - because of 2 forms of Th cells
1) Th1 for intracellular bacteria. They release IFN-Y and this activates macrophages. The macrophages release chemokines, cytokines and cytotoxins. E.g. Tuberculin reaction
2) Th2 for worm infections or allergens in the environment. They release IL-4, IL-5 and eotaxin. This activates Eosinophils, which release basic proteins, enzymes and cytokines. E.g. Allergic contact dermatitis (eg Nickel)
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
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
What happens with first exposure to pollen?
- Il-4 drives B cells to produce IgE in response to pollen antigens
- Pollen-specific IgE binds to mast cell
- Pollen-specific IgE binds to mast cell
- Second exposure to pollen
- Acute release of mast-cell contents causes allergic rhinitis
Effector mediators produced by mast cells
EARLY PHASE: •Histamine - increase vascular permeability - cause smooth muscle contraction •Leukotrienes - increase vascular permeability - cause smooth muscle contraction - stimulates mucus secretion •Prostaglandins - chemoattractants for T cells, eosinophils and basophils
LATE PHASE => Cytokines • IL-4,IL-13 - promotes Th2 promotes IgE •TNF-α - promotes tissue inflammation
Mast cell activation
Different effects on different tissues.
1) GI
•Inc. fluid secretin. inc. peristalsis
=> Expulsion of GI contents (diarrhoea, vomiting)
2) AIRWAYS
•Dec. diameter, inc. mucus secretion
=> Congestion and blockage of airways (wheezing, coughing, phlegm)
=> Swelling and mucus secretion in nasal passages
3) BLOOD VESSELS
•Inc. blood flow, inc. permeability
=> Inc. fluid in tissues causing inc. flow of lymph to lymph nodes, inc. cells and protein in tissues, inc. effector response in tissues.
Expand on eosinophils
- located in the tissues
- recruited to the sites of allergic reactions
- express FcεRI upon activation
The two effector functions of eosinophils:
1. 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.
How does allergy develop? Summary
- 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
“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”.
Atopic and Non-Atopic • Non Atopic includes - Occupational - Exercise induced - Nocturnal Asthma - Post-bronchiolitic Wheeze
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
Asthma - acute and chronic responses
ACUTE RESPONSE:
• occurs within seconds of allergen exposure
• results in airway obstruction and breathing difficulties ~ inc. mucus secretion, smooth muscle contraction.
• caused by allergen-induced mast cell degranulation in the submucosa of the airways
•There is also recruitment of cells from the circulation
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
Treatment of allergy in the clinic
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)
- 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)
- BRONCHODILATORS – Reverse acute effect of allergy on airways (e.g B2 agonist salbutamol)
- IMMUNOTHERAPY – Reverses the sensitisation to allergen by means of tolerising exposure
