Immunology 1: Hypersensitivity and allergy Flashcards
Describe an appropriate immune reaction
Immune responses occur to foreign harmful agents e.g viruses, bacteria. etc. Antigen recognition by cells of the immune system –> antibody production
Immune response will:
- Eliminate pathogens
- may cause tissue damage as a side effect (but as long as the pathogen is eliminated it will be repaired easily
What is a hypersensitivity reaction?
Occurs when immune responses are mounted against:
- Harmless foreign antigens (allergy, contact hypersensitivity)
- Autoantigens (autoimmune diseases)
- Alloantigens (serum sickness, transfusion reactions, graft rejection.
What are the classifications of hypersensitivity reactions?
Type I: Immediate Hypersensitivity
Type II: Antibody-dependent Cytotoxicity
Type III: Immune Complex Mediated
Type IV: Delayed Cell Mediated
Give examples of type I hypersensitivity reactions
Type I: immediate hypersensitivity
Anaphylaxis Asthma Rhinitis Seasonal Perennial Food Allergy
Describe primary antigen exposure in type I hypersensitivity?
Sensitisation not tolerance
IgE antibody production
IgE binds to Mast Cells & Basophils
Describe secondary antigen exposure in type I hypersensitivity?
More IgE Ab produced
Antigen cross-links IgE on Mast Cells/Basophils
Degranulation
What are the two types of type II hypersensitivity?
Organ specific autoimmune disease
- Myasthenia gravis (Anti-acetylcholine R Ab)
- Glomerulonephritis (Anti-glomerular basement membrane Ab)
- Pemphigus vulgaris (Anti-epithelial cell cement protein Ab)
- Pernicious anaemia (Intrinsic factor blocking Abs)
Autoimmune cytopenias
- Haemolytic anaemia
- Thrombocytopenia
- Neutropenia
How do you test for specific autoantibodies?
This is used for type II hypersensitivity
- Immunofluoresence
- ELISA eg anti-CCP (Cyclic Citrullinated Peptide Abs for Rheumatoid Arthritis)
Describe the process of the type III hypersensitivity
- Formation of Antigen-Antibody complexes in blood
- Complex deposition in blood vessels/tissue
- Complement & cell activation
- Activation of other cascades eg clotting
- Tissue damage (vasculitis)
1) Systemic lupus erythematosus (SLE)
2) Vasculitides (Poly Arteritis Nodosum, many different types)
Type III Immune Complex Mediated Hypersensitivity
Slide 15
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Give examples of type IV hypersensitivity responses?
- Chronic graft rejection
- GVHD
- Coeliac disease
- Contact hypersensitivity
- Many autoimmune diseases….
- Asthma
- Rhinitis
- Eczema
What are the three main varieties of type IV delayed hypersensitivity responses?
Describe the mechanisms?
Th1
Cytotoxic
Th2
Transient/Persistent Ag
T cell activation of macrophages, CTLs
Much of tissue damage dependent upon TNF & CTLs
See slides
How does inflammation arise?
Common feature of immune responses
Immune cell - recruited to sites of injury and/or infection. Activated
Inflammatory mediators - Complement, cytokines etc.
What are the features of inflammation?
Vasodilatation, increased blood flow
Increased vascular permeability
Inflammatory mediators & cytokines
Inflammatory cells & tissue damage
Signs:
- redness
- heat
- swelling
- pain
Inflammatory cell infiltrate
Cell trafficking – chemotaxis
(Neutrophils, macrophages, lymphocytes, mast cells)
Cell activation
What causes the increased vascular permeability in inflammation?
C3a, C5a, histamine and leukotrienes
What cytokines are released in inflammation?
IL-1, IL-6, IL-2, TNF, IFN-gamma
What chemokines are released in inflammation?
IL-8/CXCL8, IP-10/CXCL10
What are the risk factors for allergy?
Genetic and environmental
Genetic - polygenic.
Genes on IL-4 gene cluster = raised IgE, asthma, atopy
Genes on chr. 11q (IgE receptor) = Asthma and atopy
Genes linked to structural cells = eczema
Environmental:
- Age
- Gender
- Family size
- Infection
- Animals
- Diet
Allergy risk in the UK is increasing.
What are the levels of allergy severity?
- Mild occasional symptoms
- Chronic asthma
- Life threatening anaphylaxis
What are the types of inflammation in allergy?
- Anaphylaxis, urticaria, angioedema
type I hypersensitivity (IgE mediated) - Idiopathic/chronic urticaria
type II hypersensitivity (IgG mediated) - Asthma, rhinitis, eczema:
mixed inflammation:
1) type I hypersensitivity (IgE mediated)
2) type IV hypersensitivity (chronic inflammation)
What does the expression of disease require?
Development of sensitisation to allergens instead of tolerance (primary response - usually in early life)
Further allergen exposure to produce disease (memory response - any time after sensitisation)
Define atopy
Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema).
Describe the sensitisation of atopic airway disease?
See slides
What do eosinophils contain?
Large granules –> toxic proteins
Leads to tissue damage. They are recruited to allergic inflammation
Describe mast cells
Tissue resident cells
IgE receptors on cell surface
Crosslinking of IgEs leads to mediator release
Pre-formed
- histamine
- cytokines
- toxic proteins
Newly synthesized
- leukotrienes
- prostaglandins
What allergies are neutrophils important in?
virus induced asthma
severe asthma
atopic eczema
What do the granules of neutrophils contain and what can they synthesize?
Digestive enzymes
Synthesize:
- oxidant radicals
- cytokines
- leukotrienes
Define acute asthma?
Acute inflammation of the airway:
Mast cell activation & degranulation
Pre stored mediators released:
- histamine
Newly synthesised mediators
- prostaglandins, leukotrienes
Acute airway narrowing
What is the two-phase response to single allergen challenge?
See slides
Describe the immunopathogenesis of chronic asthma
Chronic inflammation of the airways.
1) Cellular infiltrate
- Th2 lymphocytes, eosinophils
2) Smooth muscle hypertrophy
3) Mucus plugging
4) Epithelial shedding
5) Sub epithelial fibrosis
Clinical features of asthma
Reversible generalised airway obstruction Chronic episodic wheeze Bronchial hyperresponsiveness Bronchial irritability Cough Mucus production Breathlessness Chest tightness
Response to treatment
Spontaneous variation
Reduced & variable peak flow (PEF)
Describe allergic rhinitis
Seasonal - hay fever - grass, tree pollens
Perennial - perennial allergic rhinitis
- HDM, pets
Symptoms:
- sneezing
- rhinorrhoea
- itchy nose, eyes
- nasal blockage, sinusitis, loss of smell/taste
Describe allergic eczema
- Chronic itchy skin rash
- Flexures of arms and legs
- HDM sensitisation and dry cracked skin
- Complicated by bacterial and (rarely) viral infections (early childhood, herpes simplex)
- 50% clears by 7 years
- 90% by adulthood
Describe mild and severe food allergy
Mild
- Itchy lips, mouth, angioedema, urticaria
Severe
- Nausea, abdominal pain, diarrhoea, collapse, wheeze
Anaphylaxis
What can cause food allergies in infancy?
Egg, cows milk
What can cause food allergies in children/adults?
Peanuts, nuts, shell fish, fruits, cereals, soya
What is anaphylaxis?
Severe generalised allergic reactions. It is uncommon but potentially fatal.
Generalised degranulation if IgE sensitised mast cells.
What are the symptoms of anaphylaxis?
- itchiness around mouth, pharynx, lips
- swelling of the lips, throat and other parts of the body
- wheeze, chest tightness, dyspnoea
- faintness, collapse
- diarrhoea & vomiting
- death if severe & untreated
What systems are affected in anaphylaxis?
Cardiovascular - vasodilatation, cardiovascular collapse
Respiratory - bronchospasm, laryngeal oedema
Skin - vasodilatation, erythema, urticaria, angioedema
GI - vomiting, diarrhoea
How do you investigate and diagnose allergies?
Careful history essential Skin prick testing RAST (blood specific IgE): Total IgE Lung function (asthma)
What is the emergency treatment of anaphylaxis?
EpiPen & Anaphylaxis kit
- antihistamine, steroid, adrenaline
- Seek immediate medical aid
How do you prevent anaphylaxis?
Avoidance of known allergen
Always carry a kit & EpiPen
Inform immediate family & caregivers
Wear a MedicAlert® bracelet
How do you treat allergic rhinitis?
- anti-histamines (sneezing, itching, rhinorrhoea)
- nasal steroid spray (nasal blockage)
- cromoglycate (children, eyes)
If severe: anti-IgE, anti-IL-4/-13, anti-IL-5 mAb
What is the treatment for Eczema?
- Emollients
- Topical steroid cream#
If severe: anti-IgE, anti-IL-4/-13, anti-IL-5 mAb
What is the asthma treatment plan?
See slide 47
