allergy and hypersensitivity Flashcards
what is hypersensitivity
an overreaction to harmless molecules which result in an immune response that causes inflammation and tissue damage
what is an allergy
an IgE mediated hypersensitivity reaction
what are the 4 types of hypersensitivity
- mast cell activation
- complement and phagocytes
- complement and phagocytes
- cell mediated
what is type 1 hypersensitivity
- IgE response
- antibody binding to soluble antigen
- allergic asthma, eczema
what is type 2 hypersnsitivity
- IgG
- antibody binding to associated antigen
- compliment bind and induce phagocytosis
- some drug allergies
what is type 3 hypersensitivity
- IgG
- antibody binding to soluble antigen
- serum sickness,
what is type 4 hypersensitivity
- cell mediated
- cell reactions to soluble and cell associated antigen
- macrophage activation
- eosinophil activation
- cytotoxicity
- allergic contact dermatitis, chronic asthma
what are difference roots that can cause allergy
- inhaled
- injected
- ingested
- contact
what does IgE do
- induces the response to get rid of extracellular multicellular parasites that are too large to be phagocytosed
what symptoms occur from an IgE response
- increased mucus flow, coughing, sneezing
- itch induced scratching
- diarrhoea, vomiting, increased peristalsis
where are mast cells located
in vasculature and in mucosal tissues
how do mast cells work
- they have pattern recognition receptors FceRI allowing many IgE to bind
- binding allows it to respond to allergies and release cytokines
- once you have an allergy IgE will stay bound
- contain preformed granules for immediate relief
what are the preformed granule content in mast cells
- enzymes
- toxic mediator
- cytokines
what are the synthesised granules after activation in mast cells
- cytokines
- chemokines
- lipid mediators
what do the enzymes in mast cells do
released to degrade parasites but remodels the connective tissue
what to toxic mediators in mast cells do
poison parasites but increase vascular permeability and cause muscle contraction
- recruit more immune cells but cause fluid build up
what do cytokines do in mast cells
they promote inflammation and stimulate cytokine production. activates vascular endothelium
what do the chemokines do in mast cells
attracts monocytes, macrophages and neutrophils. occur due to inflammation
what do the lipid mediators do in mast cells
- cause smooth muscle contraction, increase permeability and mucus secretion
- attracts leukocytes, amplifies production of lipid mediators, actives eosinophils and platelets
- continuously synthesised
mast cell effect intravenously
- mast cells close to the blood vessels are exposed to the antigen
- releases histamine causing systemic increase in blood vessel permeability
- systemic anaphylactic shock
mast cell effect subcutaneous
- allergen is absorbed across epithelium into the epidermis and dermis
- local release of histamine causes oedema due to dilation
- wheal and flare reaction
- only in the areas and vessels that have been exposed
mast cell effects on inhalation
- inhaled allergen passes across mucosal tissue
- globular cells are produced to create more mucus
- upper airway - increased mucus production
- ## lower airway - contraction of smooth muscle
mast cell effects on ingestion
- enters a highly vascularised mucosal tissue
- contraction of smooth muscle, increased fluid loss
- antigen enters the blood vessels causing urticaria, anaphylaxis
- can cause skin rashes
what causes anaphylaxis
- allergen entering the blood stream causes systemic activation of mast cells
- triggers widespread vascular permeability and smooth muscle constriction
- reduces BP, reducing O2 perfusion and airway contrstiction
symptoms of anaphylaxis
- feeling faint or lightheaded
- difficulty breathing
- fast heartbeat
- clammy
- confusion
- collapse
what can happen after anaphylaxis
- mast cells go into a refectory period and patients can produce similar symptoms to anaphylaxis again
- comes from recruitment of leukotrienes
what is the immediate phase of IgE response
- within first 30 mins
- mast cells reacted to presence of allergen
- release granule content increasing blood vessel permeability
what is the last phase of IgE response
- within 12 hours
- mast cells produce synthesised mediators
- results in recruitment of eosinophils, moncoytes and T cells
- exacerbation of bronchoconstriction and oedema
what cytokines are secreted in IgE response
- IL4 and IL13 - mucus and Th2 recruitment
- IL3 and IL5 - eosinophil production and recruitment
what do leukotrienes do in IgE response
- synthesised later
- promote smooth muscle contraction
- increase vascular permeability
what do histamines do in IgE response
- smooth muscle contraction
- increase vascular permeability
- increase mucus production
what do eosinophils do in IgE response
- produce type 2 cytokines
- damage the airway
- have enzymes that degrade tissue, neurotoxins and leukotrienes
what do TH2 cells do in an IgE response
- stimulate mucus production
- eosinophil recruitment
- collagen synthesis by fibroblasts
what to smooth muscle cells do in an IgE response
thicken and constrict the airway
what is given to treat anaphylaxis
- IM adrenaline
- O2
- IV fluids
why in adrenaline given in anaphylaxis
- stimulates the beta2 adrenoreceptors to relax the airway smooth muscle
- reverses cardiovascular effect via stimulation of alpha adrenergic
what immune defences are at the skin
- Langerhans cells (specialised epidermal dendritic cells)
- macrophages are tissue resident looking for infection
- mast cells are near the dermis and close to vasculature
- smooth muscle cells around vessels to allow for a response
-vascularised to allow for systemic influence
what is urticaria
a rash manifestation if IgE activation in wheel and flare lasting for 24 hrs
what causes urticaria
- immunological - food meds, environment
- non immunological - heat, cold, pressure
- autoimmune
what is angioedema
swelling of the submucosal and subdermal layers
what is the immune response in urticaria
- allergen is absorbed across the epithelium into the epidermis and dermis
- allergen triggers mast cells (IgE response) in the skin from systemic vasculature
- localised mast cell include histamines
- vasculature activated causing inflammation and oedema
what response is delayed hypersensitivity
- type IV driven by a cell response
- mediated by antigen specific T cells previously sensitised to the allergen
- non itchy rash taking 24-72 hours to occur
what are the stages of delayed type hypersensitivity
- the antigen is injected into the subcutaneous tissue and taken up and presented
- t helper effector cells are recruited and recognise the antigen
- produce cytokine which act on the vasculature
- cause recruitment of phagocytes and oedema
- high levels of inflammatory cytokines, nitric oxide and oxygen radicals
what is the response to allergic contact dermatitis
- activation of CD4 or CD8
- from small molecules entering the skin
- it binds to the intracellular antigens causing an inflammatory response
- cause little pinprick spots
what are the stages in allergic contact dermatitis
- reactive molecule binds as a hapten to an endogenous protein
- this is recognised and taken up by langerhans cells
- peptides are recognised by T helper cells which secrete IFNy
- keratinocytes are activated and secrete pro-inflammatory cytokines and chemokines
- cytokines from keratinocytes and T cells activate macrophages
- more inflammation and macrophages release NO
what does hapten mean
combination of reactive molecule and protein
what is atopic dermatitis
- inflammation similar to contact dermatitis
- not localised and spread across all the body
- dry skin, or scaly patched usually at joints
what causes atopic dermatitis
- mix of reduced barrier function, immune dysregulation and environment
- skin is deficient in lipid molecules and antimicrobial peptides
what is the cause of a drug reaction
developed IgE antibodies on initial exposure and then second exposure triggers allergic reaction
why do certain drugs cause reactions
due to their ability to act as haptens or covalently bind to receptors
what are reactions to adverse drug reactions
- purpura
- blistering lesions with mucous membrane involvement
- circumscribed erythematous raised lesion
what is purpura
vasculitis or drugs induced thrombocytopaenia
what is the type 1 mechanism in drug reactions
- IgE mediated urticaria
- mainly on trunk, sometimes anaphylactic
- drug triggers systemic mast cell activation causing urticaria
- body systemic vascular activation causing anaphylaxis
what is the type 2 mechanism of drug reactions
- cytotoxic, haemolytic anaemia, neutropoenia, thrombocytopaenia
- drug binds to surface of erythrocytes and recognised by IgG
- complements can be activated and IgG directs macrophage phagocytosis
what is the type 3 mechanism of drug reactions
- serum sickness, vasculitis, urticaria
- antigen and IgG pass into the tissue
- triggers complement and active mast cells
- mast cell degranulation increases permeability, inflammation, phagocytosis and vessel occlusion
how doe type 5 mediated reactions occur
- MHC presentation of drug molecules to T cells with cytokine and inflammatory mediator release
- depending on t cell response outcome is then classified by mechanistic cells
