Hypersensitivity &asthma Flashcards
Define hypersensitivity
- Immunologically driven host-tissue damaging process’
- Immunologically driven tissue-irritating process
Outline the innate immune system
- First lines of defence, general, rapid response
- Complement system
- neutrophils, basophils, eosinophils, mast cells, NKs
- Macrophages, dendritic cells
- APCs: macrophages, dendritic cells, follicular DCs & B cells
Outline the adaptive immune system
- Directed by the innate immune cells, antigen specific
- memory, late response
- T& B cells
- Antibodies: immunoglobulins(Ig) IgA, IgG, IgM,IgE,IgD
Outline the different types of hypersensitivity:
1.) Type I : immediate hypersensitivity (Allergy-Anaphylaxis& Atopy)
-Non-microbial environmental antigens that are innocuous. Response within minutes mediated by IgE-mast cells
2.) Type II: antiBody mediated
-IgM, IgG antibodies against cell surface/extracellular matrix complement-mediated
3.) Type III: Immune Complex mediated
-soluble immune complexes antigen-IgM or antigen-IgG
-complement mediated
4.) Type IV: cell mediated( Delayed)
-CD4& CD8 cells. cell killing & cytokine-mediated inflammation. 24-48h
-Takes longer to develop
ABCD pneumonic
What are the characteristics of the main allergens in type I hypersensitivity?
- Individuals are rapidly exposed to them
- They do not induce macrophages/ dendritic cells typical responses driving Th1/Th17 (like microbes do)
Explain type I hypersensitivity
- Immediate hallmarks= IgE production & activation of Th2 cells; mediated by IgE- mast cells
1. ) Mast cells: - Cross-linking of 2 adjacent IgE molecules triggers mast cell activation
2. ) may be triggered by inhaled allergens
3. ) may be triggered by dust mites, pets, pollen, fungi, food allergies e.g peanuts; drugs such as antibiotics or chemotherapeutics
What are the 2 main mediators of mast cells
1.) Storage granules:
-Histamine: increased vascular permeability; smooth muscle contraction
-Tryptase: Tissue remodelling; increased mucus secretion
2.) De novo synthesis:
-Prostaglandins: increased vascular permeability
-Leukotrienes: smooth muscle contraction
-Cytokines: vasodilation
Systemic anaphylaxis eventually results. This is lethal
What actions make up ‘wheal and flare’ responses
-Vasodilation
-Vascular leak
These are caused by histamine
What interleukin activates Eosinophils
IL-5.
This then causes a release of granules, leading to tissue damage
What is systemic anaphylaxis
- Type I hypersensitivity of the whole body
- can be lethal
What are the symptoms of type I hypersensitvity in the following organs:
- ) Lung
- )Nose
- ) Eye
- ) Skin
- ) Gut
- ) asthma, wheezing
- ) rhinitis, sneezing, runny nose
- ) Conjunctivitis
- ) Atopic dermatitis
- ) Food allergy
What lab tests can we use to help diagnose type I hypersensitivity
- Total IgE (.100IU/mL)
- specific IgE raised (e.g RAST)
- Tryptase levels-transient (24-48h)
- Can also use the skin prick test( >3mm wheal- swelling)
What is RAST?
Radio-allergosorbent test
- done on a sample of blood
- Detection of label is proportionate to the amount of IgE specific for the antigen
Give examples of type I hypersensitivity.
- Pruritus( itch)
- Urticaria(hives)
- Allergic rhinitis (hay fever)
- Asthma- immediate asthma
- Systemic anaphylaxis- whole body
What do you expect to see in a positive skin prick test
-When exposed to the allergen a wheal & flare should result
Wheal & flare:
-leakage of plasma& protein (edema)
-vasodilation& congestion
What issues may be associated with/ the cause of asthma?
- Bronchial hyperresponsiveness
- Mucous cell metaplasia
- Thickening of the bronchial wall
- Bronchoconstriction
- Inflammation
What are the main characteristic features of asthma?
- Variable airways narrowing–> leading to airflow obstruction that is reversible spontaneously or with treatment
- Non-specific airways hyperresponsiveness to innocuous stimuli ( cold air, irritants, pollutants) —> leading to bronchoconstriction. Always present
- Mucosal inflammation and airways remodelling
What are the different phenotypes of asthma
- ) Allergic asthma: most easily recognised. Usually commences in child hood. Associated witth past/family history of allergic disease. Usually presents eosinophilic airway inflammation. Good response to ICS
- ) Non-allergic asthma: sputum may be neutrophilic, eosinophilic, or with few inflammatory cells. Less response to ICS
- ) Late-onset asthma: more common in women. Tendency to non-allergic; high doses of ICS required
- ) Asthma with fixed airflow limitation: long-standing asthma, airflow limitation thought to be due to airway wall remodelling
- ) Asthma with obesity: prominent respiratory symptoms; little eosinophilia
Give e.g’s of type II hypersensivity
- Grave’s disease
- Insulin-resistant diabetes
- Myasthenia gravis (Ab-ach)
- Immune hemolytic anemia
- Immune thrombocytopeic purpura
- Glomerulonephritis
Give e.g’s of Type IV hypersensitivity
- Inflammatory bowel disease
- Crohn’s
- Contact sensitivity (Ni+2)
- Asthma
- Autoimmune myocarditis: myosin heavy chain protein
- Type I diabetes mellitus: destruction of islet cells
Give e.g’s of type III hypersensitivity
Seum sickness: -complexes in small arteries -Vasdculitis -renal glomeruli -nephritis -joints synovia -arthiritis Systemic immunologic diseases: -SLE -nephritis -arthiritis -polyarteritis nodosa -Poststreptococcal glomerulonephritis
Explain the role of inflammation in the pathology of asthma
- ) Inflammatory infiltrate: inflammatory cell recruitment, Th2 cells, mast cells & eosinophils
- ) Mucosal oedema: bronchial microvascular leak
- ) Mucus hypersecretion: blockage of airways by mucus plugs
- ) Bronchial smooth muscle contraction: action of inflammatory mediators
Explain the role of remodelling in the pathology of asthma
Persistent alterations in airways structure
- ) Epithelial cell damage: leaky epithelium
- ) Reticular basement membrane thickening
- ) Airway smooth muscle thickening
- ) Submucosal mucus gland hypertrophy
What is the early and late response in asthma
Early response: Hypersensitivity I
Late response: Hypersensitivity IV
What are the associated risks of asthma ?
Host factors(predisposition) -genetic -atopy(+ve skin prick tests-type I) Environmental factors ( precipitate asthma exacerbations) -allergens -occupational sensitizers( vehicle spray painting, baking) -air pollutants -respiratory viruses( common cold) -exercise -drugs (aspirin, NSAIDs)
What are Curschmann spirals?
-Mucus plugs
-Casts from small bronchi
-Dangerous as it blocks air exchange &medication
(neutrophilic asthma?)
What are charcot-leyden crystals ?
- Needle-shaped
- from breakdown of eosinophils
