Hypersensitive reactions asthma and allergy Flashcards
What is hypersensitivity and what are the 4 types?
An inappropriate immune response to non-infectious antigens that results in tissue damage and disease - Type 1: immediate hypersensitivity Type 2: cytotoxic hypersensitivity Type 3: serum sickness and Arthus reaction Type 4: delayed-type hypersensitivity, contact dermatitis
What is the arthus reaction and what occurs as a result?
The Arthus reaction is a rare adverse reaction that usually occurs after vaccination with large and more severe local reactions, belonging to type Ⅲ hypersensitivity reaction Antigen injected into the arm, excess of antigen as a result. This results in the formation of immune complexes. Immune complexes activate complement which in turn activates mast cells. 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, haemorrhage, and the appearance of purpura.
What is the serum sickness?
caused by large intravenous doses of soluble antigens (e.g. drugs) 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
Summary photo of the 4 types of hypersensitivity
What 2 phases does an allergic respose have and what mediates each phase?
Allergic responses have an early and late phase
Early is mediated by mast cells
Late is mediated by T cells
What effector mediators are produced by mast cells and what effect do they have?
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 promotes Th2
IL-23 promotes IgE
TNF-alpha promotes tissue inflammation
What are some properties of eosinophils and what effector functions do they have?
Eosinophils:
located in the tissues
recruited to the sites of allergic reactions
express FceRI upon activation
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.
A summary of how an allergy develops
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 Dendritic Cells 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
What is 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
Non-allergic asthma, or non-atopic asthma, is a type of asthma that isn’t related to an allergy trigger like pollen or dust, and is less common than allergic asthma. The causes are not well understood, but it often develops later in life, and can be more severe.
What is allergic 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
How is allergic asthma characterised?
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
What is the acute response to allergic asthma?
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
What is the chronic response in allergy asthma?
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
What are some treatments of allergy?
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)
BUT MOSTLY we use:
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
