Hypersensitivity and Allergy Flashcards
Atopy is…
A form of allergy in which there is a hereditary or constitutional tendency to develop hypersensitivity reactions in response to allergens (atopens)- individuals with this predisposition, and conditions provoked in them by contact with allergens, are described as atopic
What does an appropriate immune reaction involve
- Involves antigen recognition by cells of the immune system and antibody production
Antigen recognition + ‘danger’ signals =
IMMUNE REACTIVITY
Antigen recognition + no ‘danger’ signals =
Tolerance
What leads to tolerance
Antigen recognition + no ‘danger’ signals
What leads to IMMUNE REACTIVITY
Antigen recognition + ‘danger’ signals
HYPERSENSITIVITY REACTIONS:
Occur when immune responses are mounted against: (3)
- Harmless foreign antigens (allergy/contact hypersensitivity)
- Autoantigens (autoimmune diseases)
- Alloantigens (serum sickness, transfusion reactions, graft rejections)
Immune response against what causes allergy/contact hypersensitivity
Harmless foreign antigens
Immune response against what causes serum sickness, transfusion reactions, graft rejections
Alloantigens
Alloantigens are against what? (3)
serum sickness, transfusion reactions, graft rejections
4 types of hypersensitivity reactions?
- Type I: Immediate Hypersensitivity
- Type II: Antibody-dependent Cytotoxicity
- Type III: Immune Complex Mediated – complex of antibody and antigen causing disease
- Type IV: Delayed Cell Mediated
What is a type 1 hypersensitivity reaction (summarised)
Immediate Hypersensitivity
What is a type 2 hypersensitivity reaction (summarised)
Antibody-dependent Cytotoxicity
What is a type 3 hypersensitivity reaction (summarised)
Immune Complex Mediated – complex of antibody and antigen causing disease
What is a type 4 hypersensitivity reaction (summarised)
Delayed Cell Mediated
Examples of type 1 hypersensitivity? (4)
Anaphylaxis, asthma, rhinitis (seasonal or perennial (long lasting, year round i.e. constant)), food allergies
Explain 2 exposure mechanism of T1 hypersensitivity
1st EXPOSURE:
- Sensitisation (allergy) not tolerance (no allergy)
- Sensitisation involves IgE antibody production
- IgE binds to Mast Cells and Basophils
2nd EXPOSURE:
- More IgE Ab produced
- Antigen cross-links IgE on Mast Cells/Basophils
- Leads to degranulation and release of inflammatory mediators
What Ab does sensitisation involve
- Sensitisation involves IgE antibody production
- IgE binds to Mast Cells and Basophils
What cells do IgE act on in T1 hypersensitivity
Mast Cells/Basophils
Examples of diseases caused by T2 hypersensitivity reactions? (4+3)
- Myasthenia gravis (anti-ACh receptor antibodies)
- Glomerulonephritis (anti-glomerular basement membrane antibody)
- Pemphigus vulgaris (anti-epithelial cell cement protein antibody)
- Pernicious anaemia (antibody mediated blood cell destruction such as below)
- Haemolytic anaemia
- Thrombocytopenia
- Neutropenia
What autoimmune target when attacked causes pemphigus vulgarisms
autoimmune attack of an antibody that cements epithelial cells together
What autoimmune target when attacked causes bullies pemphigoid
antibodies are against basement membrane proteins
Difference between pemphigus vulgarisms and bulls pemphigoid?
the blisters tend to be more robust because they are due to a deeper inflammation in the skin than pemphigus
What is used to test for specific antibodies in T2 HS (2)
- Immunofluorescence
- ELISA (enzyme-linked immunosorbent assay, e.g. anti-CCP cyclic citrullinated peptide antibodies for rheumatoid arthritis)
Examples of diseases caused by T3 hypersensitivity reactions? (3)
- Tissue damage (vasculitis)
Systemic lupus erythematosus (SLE)
Vasculitides (Poly Arteritis Nodosum, many different types)
What causes T3 HS?
- Formation of Antigen-Antibody complexes in blood
Explain mechanism of T3 hypersensitivity reactions (4 stages)
- Formation of Antigen-Antibody complexes in blood they can’t get through small blood vessels very easily
- This causes complex deposition in blood vessels/tissue
- This leads to complement and cell activation
- Activation of other cascades e.g. clotting
- Tissue damage (vasculitis)
Examples of T4 HS reactions? (8)
- Chronic graft rejection
- GVHD (Graft vs host disease)
- Coeliac disease
- Contact hypersensitivity
- Many autoimmune diseases
- Asthma (this and below are Th2 mediated, above is Th1 mediated )
- Rhinitis
- Eczema
3 main varieties of T4 HS reaction?
- Th1
- Cytotoxic
- Th2
What characterises TH1 mediated T4 HS?
Characterised by producing lots of gamma-interferon- the most important type in hypersensitivity reactions
What characterises TH2 mediated T4 HS?
Releases IL-4, IL-5 and IL-13:
Which IFN is most important in hypersensitivity
gamma-interferon
Explain TH2 mediated T4 HS?
- Th2 mediates allergic inflammation e.g. asthma etc.
- Mechanisms involve either a transient antigen presence or a persistent antigen
- T cells then activate macrophages and CTLs
- Much of the tissue damage is dependent upon TNF, hence why neutralising TNF has marked clinical benefits
examples of Th1 mediated diseases in T4 HS? (5)
- Chronic graft rejection
- GVHD (Graft vs host disease)
- Coeliac disease
- Contact hypersensitivity
- Many autoimmune diseases
examples of Th2 mediated diseases in T4 HS? (3)
- Asthma
- Rhinitis
- Eczema
Explain mechanism of T4 mediated HS? (3)
- Transient/Persistent antigen
- T cell activation of macrophages, CTLs
- Much of tissue damage dependent upon TNF & CTLs
What is the antigen in T2 HS reactions?
Cell surface or matrix bound proteins
What is the antigen in T3 HS reactions?
Soluble antigens
What causes asthma? Ig involved, what cell is involved, what is induced, and what does this produce?
caused by IgE binding to mast cells and by the induction of T cells producing Th2 type cytokines
4 signs of inflammation?
- Vasodilation, increased blood flow leads to redness
- Increased vascular permeability Caused by C3a, C5a, histamine and leukotrienes leads to swelling
- Inflammatory mediators and cytokines
- Inflammatory cells and tissue damage leads to pain
5 cytokines involved in inflammation? (3 IL, 2 other)
IL-1, IL-2, IL-6, TNF, IFN-gamma
Chemokine involved in inflammation? (2)
IL8/CXCL8, IP-10/CXCL10
What mediates cell trafficking?
chemokines
Which Ig is linked to atopy?
IgE
Which gene cluster and chromosomes are linked to atopy
IL-4 gene cluster (Chr 5)
chromosome 11q
Environmental risk factors for atopy? (6)
- Age allergies rare in infancy, peaks in teens, reduces in adulthood
- Gender Asthma is more common in males in childhood, females in adulthood
- Family size More common in small families
- Infections Early life infections protect against atopy
- Animals Early exposure to animals protects against atopy
- Diet Breast feeding, anti-oxidants and fatty acids protect against atopy
Why is the prevalence of allergies largely increasing? (2)
Prevalence of allergies are increasing largely due to change in the environment (less grass n trees n shit) and because infectious diseases are a lot less common now than they were back in the day
What types of inflammation is seen in T1 HS? What mediates this?
Anaphylaxis, urticarial, angioedema
Asthma, rhinitis, eczema
IgE
What types of inflammation is seen in T2 HS? What mediates this?
Idiopathic/chronic urticaria type II hypersensitivity (IgG mediated)
Asthma, rhinitis, eczema
IgG mediated)
What types of inflammation is seen in T4 HS? What mediates this?
Asthma, rhinitis, eczema
What mediates inflammation in T2 HS?
IgG
Explain how sensitisation occurs in atopic airway disease starting with CD4 T cells being activated
CD4+ T cells are activated by an antigen presenting cell, they become specific to the presented antigen
- They could become Th1 (producing IFN-gamma leading to autoimmune disease)
- They could become Th2 cells that lead to the activation of B cells which will lead to allergic response
Th2 cells then proliferate and release IL4 and IL13 which stimulates proliferation and differentiation of B cells and causes them to produce IgE instead of IgG which is specific to that peptide of allergen.
If the T cell was presented with a harmless antigen, it may become a regulatory T cell leading to tolerance
Explain what happens in the second exposure of T1 HS starting with allergens being presented
allergens are presented by the APCs to the memory Th2 cells
- These release IL-5 which activates and causes degranulation of eosinophils releasing bare mediators of inflammation
- Th2 cells also release IL-4 and IL-13, which stimulate the production of IgE by plasma cells
- The IgE then becomes mobilized onto the surface of mast cells
- The antigens then cross-link with the IgE on the surface of the mast cells and cause degranulation
- There is a massive release of inflammatory mediators, which gives rise to the effects seen in an allergic reaction
What does IL 5 cause
activates and causes degranulation of eosinophils releasing bare mediators of inflammation
What IL does a Th2 cell release in HS
IL-5, IL-4 and IL-13
What does IL4 and IL13 do
stimulate the production of IgE by plasma cells
What 3 lymphocytes are recruited during allergic reactions
EOSINOPHILS
MAST CELLS
NEUTROPHILS
Number of lobes in the nucleus of an eosinophil?
2
Eosinophils are mainly found where
In tissues
Receptors on the surface of mast cells?
IgE
What do mast cells release on activation via IgE (5)
Pre-formed Histamine, cytokines, toxic proteins
Newly synthesized Leukotrienes, prostaglandins
What newly synthesised molecules do mast cells release? (2)
Leukotrienes, prostaglandins
What pre-formed molecules do mast cells release? (3)
Histamine, cytokines, toxic proteins
Neutrophils cause what types of asthma (3)
Virus induced, severe asthma and atopic eczema
of Lobes in the nucleus of neutrophils?
Polymorphonuclear, so quite a few
Granules of neutrophils contain what, and what do neutrophils synthesis (4)
digestive enzymes Oxidant radicals
Cytokines
leukotrienes
Which HS types are involved in asthma?
is a mixture of type 1 and type 4
Granules of eosinophils contains what?
- toxic proteins
What cell mediates acute airway narrowing in asthma? (cell and what it releases (4))
- Mast cell activation and degranulation releases histamines (pre-stored mediators) and prostaglandins and leukotrienes (newly synthesized mediators)
Acute Airway narrowing caused by What 3 processes?
- Vascular leakage leading to airway wall oedema
- Mucus secretion filling up the lumen
- Smooth muscle contraction around the bronchi
What 4 things occur during chronic inflammation of the airways?
- Smooth muscle hypertrophy
- Mucus plugging
- Epithelial shredding
- Sub-epithelial fibrosis (if the inflammation has persisted for a long time) causing permanent airway narrowing from scarring.
What 2 cells infiltrates the airways during inflammation?
Th2 lymphocytes and eosinophils
9 clinical features of asthma?
- Reversible generalized airway obstruction Causes chronic episodic wheeze
- Bronchial hyper-responsiveness (they are much more sensitive to bronchial irritants
- Cough
- Mucus production
- Breathlessness
- Chest tightness
- Response to treatment
- Spontaneous variation
- Reduced and variable peak expiratory flow (PEF)
What are the 2 responses in asthma?
early response which is immediately after inhalation of the allergen and the late response which is cell mediated
How much after inhalation of allergen can the large response occur
5 hours give or take
what causes the early response to asthma?
largely due to mast cell activation
what causes the late response to asthma? (2)
due to neutrophils and eosinophils.
2 types of allergic rhinitis?
- Seasonal- e.g. hay fever (grass and tree pollens)
- Perennial- house dust mites, animal allergens etc.
Symptoms of allergic rhinitis? (4)
- Sneezing
- Rhinorrhoea
- Itchy nose and eyes
- Nasal blockage, sinusitis, loss of smell/taste
What can eczema lead to?
- Can lead to house dust mite sensitization The dust mite proteins can get through the dry, cracked skin
what HS type is food allergy? What mediates. this reaction?
Type I (IgE mediated) hypersensitivity reaction
Common food allergies?
Eggs, cow’s milk in babies n toddlers
Peanuts, shellfish, nuts, fruits, cereals, soya in children n adult
Mild symptoms of food allergy?
- Itchy lips and mouth
- Angioedema
- Urticaria (hives)
Severe symptoms of food allergy? (4)
- Nausea
- Abdominal pain
- Diarrhoea
- Anaphylaxis
What mediates anaphylaxis?
Generalised degranulation of IgE sensitized mast cells
Symptoms of anaphylaxis? (6)
- Itchiness around mouth, pharynx and lips
- Swelling of lips, throat and other parts of the body
- Wheeze, chest tightness and dyspnea
- Faintness, collapse
- Diarrhea &vomiting (D&V)
- Death if severe and untreated
Effects of anaphylaxis on body systems? (4)
CVS Vasodilation, cardiovascular collapse
Respiratory Bronchospasm, laryngeal oedema
Skin Vasodilation, erythema, urticarial, angioedema
GI D&V^
Investigation and diagnosis of anaphylaxis? (5)
- Careful history is essential
- SKIN PRICK TESTING
- RAST (radioallergosorbent test) Tests for the amount of specific IgE antibodies in the blood
- Measure total IgE
- Lung function (in asthma)
Emergency treatment for anaphylaxis? (severe and mild)
- EpiPen and anaphylaxis kit (antihistamine steroid and adrenaline)
- Emergency treatment if mild = antihistamine (can be backed up with a steroid injection)
- Emergency treatment if severe = ADRENALINE
Methods of Prevention of anaphylaxis? (4)
- Avoidance of known allergen
- Always carry EpiPen and anaphylaxis kit
- Inform immediate family and caregivers
- Wear a MedicAlert bracelet
Treatment for rhinitis? (2)
Anti-histamines
Nasal steroids
Treatment for eczema??
Emollients for moisture
Topical steroid cream
What is salbutamol used for
Asthma
What is the MoA of salbutamol
Short acting b2 agonist
4 stems to treat asthma?
1 - short acting beta 2 agonist (salbutamol)
2 - inhaled steroid (budesonide)
3 - Add therapy (long acting B2 agonist or leukotriene antagonist
And inhaled high dose steroids
4 - add oral steroids, prednisolone and anti-IgE, Anti-IL4/13 and anti-IL5 mAbs
How does immunotherapy work in building tolerance?
- Make people develop tolerance by exposing them to small amount of the allergen they’re allergic to
What is immunotherapy effective in building tolerance for?
for single antigen hypersensitivities
2 types of immunotherapy?
- Subcutaneous immunotherapy (SCIT)
- Sublingual immunotherapy (SLIT)
