lecture 26/27 - hypersensitivity diseases Flashcards
What is hypersensitivity and how does it correlate to atopy?
Hypersensitivity: excessive immune response from allergic reactions
Atopy: tendency to develop immediate hypersensitivity mediated by igE antibodies to various exogenous antigens
What is a type I hypersensitivity? What defines it?
20 minute stimulation-symptom development
IgE reactant, soluble antigen and mast cell activation
What are the reactions associated with type I hypersensitivities? What allergens are commonly associated?
Systemic anaphylaxis: drugs, venom, food, serum
Acute urticaria: animal hair, insect bites and allergy testing
Seasonal rhinoconjunctivitis: pollens, dust mite feces
Asthma: danders, pollens, dustmite feces
Foods
Describe the steps involved in antigen sensitization
First exposure → antigen activation of TH2 and stimulation of IGE class switching due to il4/IL13 secretion→ IgE production → dinding of IgE to Fc-epsilon-RI on mast cells→ increases half life of IgE → cross linking of antigen to IGEsecretion of proinflammatory mediators upon antigen binding → inflammatory response
What is the difference between the early and late phase reactions?
Early, withing seconds
pre-formed/fast release
Histamine: increases vascular permeability
Eosinophil and neutrophil chemotactic factors
Late, 1-6 hours, newly synthesized
Chemokines (macrophage inflammatory proteins MIP-1-alpha) attracts neutrophils to site of inflammation
Cytokines IL 3+5 induce more eosinophil activation and 4/13 induce more Th2 activation
Describe the antigen processing of inhaled antigens in the context of cysteine protease
Enzyme Der p 1 cleaves occludin in tight junctions and enters mucosa → taken up from antigen presentation via phago or endocytosis → dendritic cell primes cell in lymph node → Th2 induces B cell switch to IgE production→ plasma cell travels back to mucosa and produces Der specific antibodies → IgE binds mast cell receptor → Der binds to mast cell → degranulation of mast cell to cause allergic reaction
Describe allergic rhinitis
Inhaled antigens enters mucosa and activates mast cells locally → mast cell activation causes blood vessel permeability and activation of epithelium → eosinophils are recruited from blood and enter nasal passages with mucus
Irritation due to histamine release
Describe bronchial asthma
Lower airway mast cell activation → chronic bronchial inflammation and eosinophilia due to eosinophils and Th2 cytokines
LTC4 a leukotriene is also a major bronchoconstriction mediator
Corticosteroids block production of inflammatory cytokines
Mast cell stabilizers to decrease effect of mast cells
Difference between acute and chronic response
Urticaria: mild, treatment with antihistamines
Atopic eczema: chronic and late stage dependent, treated with corticosteroids
What is anaphylaxis?
Super systemic activation of mast cells, inducing systemic vasodilation → drop in BP
Treatment with epinephrine
What is a skin prick test
Low dose subcutaneous antigen → mast cell activation → vascular permeability and localized swelling to determine allergies
What is type II hypersensitivity?
Antibody mediated
Antibodies react to cell surface pathogens, complement and /nk play roles
Happens in ~60 minutes
NK kill antibody coated targets and cause damage and contributing to inflammation/
Complement pathway activated, C5a and C3a production → chemotactic→ white blood cell recruitment → inflammation → MAC complex → lysis
Ex. blood transfusions
What is the anti-rhesus D response?
Hemolytic disease of the newborn → IgG
Rh(-) with Rh(+) fetus, RBCs leak into mother during labour, RBCs induce anti D antibodies → mother anti-D attacks fetus during second pregnancy (ie second exposure)
Treatment with exogenous antiD to destroy fetal Rh(+)
What are type 3 reactions?
Immune complex mediated, takes 1-2 hours
IgG react to circulating antigens with complement and Fc receptors playing a role
Localized injection of antigen → local immune complex formation to activate complement → C5a binding and sensitizing mast cell to respond to co plex → activation of mast cell receptors to induce degranulation → local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion
Immune complex deposition giev rise to cutaneous vasculitis
Ex arthus reaction and serum sickness
What is type IV?
Mediated by Th1 cells, cytokines and macrophages taking about 2 days
Antigen injected into subcutaneous tissue → processing by local antigen presenting cells → Th1 effector cell recognizes antigens and releases cytokines which act on vascular endothelium → recruitment of phagocytes and plasma to site of injection → visual lesion and inflammation
