Immune 1 - Hypersensitivity and Allergy Flashcards
What are the 4 types of hypersensitivity
Type 1: Immediate hypersensitivity (IgE mediated)
Type 2: Antibody-dependent cytotoxicity
Type 3: Immune complex mediated
Type 4: Delayed cell mediated
Type 1 hypersensitivity (immediate) involves which forms of allergY
- Anaphylaxis
- Asthma
3, Rhinitis (seasonal and perennial) - Food allergy
Explain how immediate hypersensitivity works
Initial antigen exposure:
- Sensitation occurs (not tolerance)
- IgE antibody production
- IgE binds to mast cells and basophils
Secondary antigen exposure:
- More IgE antibody produced
- Antigen crosslinks IgE on mast cells/basophils
- Degranulation and release of mediators
Describe some organ specific presentations of Type 2 (antibody dependent hypersensitivity)
- Myasthenia graves (anti-ACh receptor Ab)
- Glomerulonephritis (anti-glomerular basement membrane Ab)
- Pemphigus vulgaris (anti-epithelial cell cement protein Ab)
- Pernicious anaemia (intrinsic factor blocking Ab)
Can also get autoimmune cytopenias
What tests can be done for specific antibodies?
- Immunofluorescence
2. ELISA (e.g. anti-CCP Abs for rheumatoid arthritis)
Explain how Type 3 hypersensitivity works (Immune complex mediated)
- Antigen-Ab complex forms in blood
- Complex deposition in blood vessels/tissue
- Complement and cell activation at site of deposition
- Activation of other cascades (e.g. clotting)
- Tissue damage (vasculitis)
Common sites of vasculitis = lungs, skin, joints, renal
Which diseases are based of type 3 hypersensitivity?
SLE, vasculitides (polyarteritis nodosum)
Describe some type 4 sensitivity disorders (delayed hypersensitivity)
- Chronic graft rejection
- GVHD
- Coeliac disease
- Contact hypersensitivity
- Autoimmune diseases
All above are Th1 mediated
Asthma, rhinitis and eczema are Th2 mediated and can be type 4 too
In type 4, much of the tissue damage is dependent on?
TNF and CTLs
What are the signs of inflammation
Redness, heat, swelling, pain
What contributes to the increased vascular permeability in inflammation.
What are the important cytokines
What are the important chemokines
Increased vascular permeability:
C3a, C5a, histamine and leukotrienes
Cytokines: IL1, IL6, IL2, TNF, IFN-y
Chemokines: IL8, IP-10
What are chemokines
Cytokines that attract inflammatory cells
Which immune cells are important in inflamamtion
Neutrophils, macrophages, lymphocytes and mast cells (but mast cells = th2 activated)
Allergy has a polygenic component - explain
- Genes of IL4 cluster on Chr 5 linked to raised IgE, asthma, atopy
- Genes on Chr 11q (IgE receptor) linked to atopy and asthma
- Genes linked to structural cells linked to eczema (filaggrin) and asthma (IL-33, ORMDL3, CDHR3)
Describe some environmental risk factors for allergy
Age Gender Family size Infections (early infections protect) Animals Diet
Type 1 hypersensitivity is IgE mediated. What Ig mediates Type 2
IgG
Describe the types of inflammation in allergy
Type 1 (IgE): anaphylaxis, urticaria, angioedema
Type 2 (IgG): idiopathic/chronic urticaria
Asthma, rhinitis, eczema = mixed inflammation from Type1 hypersensitivity and type 4 hypersensitivity (Type 4 = th2 driven)
Where do most eosinophils reside
In tissue - they are recruited in allergic inflammation
Bilobed nuclei
Eosinophils contain large granules w/ toxic proteins) - leads to tissue damage
What receptors do mast cells have on their surface
IgE
Crosslinking of Mast cells and IgEs leads to mediator release
Mediator release involves preformed histamine/cytokine/toxic protein and newly synthesised leukotrienes and prostaglandins
Neutrophils make up 55-70% of blood leukocytes - and have polymorphonuclear cells. When are they important?
What can they synthesise
Important in virus induced asthma, severe asthma, atopic eczema
Their granules contain digestive enzymes
Neutrophils can also synthesise oxidant radicals, cytokines, leukotrienes
Describe the acute immunopathogenesis of asthma
Acute inflammation of the airways
Mast cell activation and degranulation releases mediators
The mediators cause acute airway narrowing by causing: Airway wall oedema, mucus secretion and SM contraction
Describe the chronic immunopathogenesis of asthma
Chronic inflammation of the airways
Cellular infiltrate including Th2 lymphocytes and eosinophils
Smooth muscle hypertrophy, mucus plugging, epithelial shedding, sub epithelial fibrosis
What are the clinical features of asthma
- Reversible generalised airway obstruction (chronic episodic wheeze)
- Bronchial hyper responsiveness (bronchial irritability)
- Cough
- Mucus production
- Breathlessness
- Chest tightness
they respond to treatment, have spontaneous variation and reduced/variable peak flow
Describe allergic eczema
Chronic itchy skin rash on flexures of arm and legs
House dust mite sensitisation and dry, cracked skin
Complicated by bacterial and viral (rare) infections
90% clears by adulthood
Describe anaphylaxis
Severe generalised allergic reaction - caused by generalised degranulation of IgE sensitised mast cells
Describe investigation and diagnosis of allergy
- Careful history
- Skin prick testing
- RAST (blood specific IgE)
- Total IgE
- Lung function (Asthma)
What is the treatment of anaphylaxis
Emergency : epipen and anaphylaxis kit (antihistamine, steroid, adrenaline + seek immediate medical aid)
Prevention: avoid allergen, carry epipen, inform immediate family and caregivers, wear medic alert bracelet
What is the treatment for allergic rhinitis
- Anti-histamines (treats sneezing, itching, rhinorrhoea)
- Nasal steroid spray (nasal blockage)
- Cromoglycate (prevents degranulation)
What is the treatment for eczema
- Emollients
- Topical steroid cream
If severe- anti-IgE, anti-IL4/13, anti-Il5 mAb
Describe asthma treatment
Step 1: short acting B2 agonist drug (salbutamol)
Step 2: Inhaled steroid (beclomethasone/budesonide)
Step 3: Long acting bronchodilators (leukotriene antagonist) / high dose inhaled steroids
Step 4: Add courses of oral steroids, SLIT, azithromycin (prednisolone), anti-IgE, anti-Il5, Anti-il4/13 mAbs
Describe immunotherapy
Useful for single antigen hypersensitivities (e.g. venom, pollens, dust mites)
Subcutaneous immunotherapy (SCIT) - done for 3 years
Sublingual immunotherapy (SLIT) - can be taken at home, 3 years
