allergy and hypersensitivity reactions

Introduction

many people have allergies which may be to medicines, biological substances such as from bee stings, components in foods, contact substances or inhaled in the air
traditionally the various types of allergic reactions have been classified under the Gell and Coombs hypersensitivity reactions (see below)
recently it has also been proposed that sensory nerves may “remember” protease allergens and also become a source of initiating reactions on subsequent exposures
- protease allergen exposure induced sustained mechanistic target of rapamycin complex 1 (mTORC1) kinase signaling and transcriptional activator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)-associated mitochondrial remodeling in sensory neurons, establishing a metabolically primed state with enhanced neuronal responsiveness. Upon allergen re-exposure, this state drove enhanced itch, CD301b+ dendritic cell migration, and Th2 cell differentiation¹⁾

antigen binds to Antigen presenting Cell (APC) ⇒ activates T Helper cell ⇒ IL-4 production ⇒ B IgE type ⇒ IgE production

mast cell degranulation due to either:
- IgE from priming event binds antigen complex
  - it appears a protein, neuritin, prevents the over-production of IgE and thus allergies, anaphylaxis, asthma and many auto-immune conditions could be the result of a deficiency of neuritin according to researchers at the Australian National University (ANU) in 2021
- direct degranulation via C3alpha/C5alpha, morphine, codeine;
⇒ immediate granule release (~20 min)
- histamine, etc
- ⇒ H1 effector ⇒ increased permeability; urticaria; asthma;
- ⇒ H2 feedback ⇒ down-regulation
- ⇒ decreased mast cell degranulation
- ⇒ decreased PMNL activity, etc;
- ⇒ activation phospholipase A2 (slow ~8 hrs, inhib. by NSAID/steroids)
- ⇒ PG, thromboxane, SRS-A, leukotriene production;

see also:
- food allergy
strict avoidance of precipitant - may need allergy testing to ascertain
patient to have an EpiPen on hand at all times
patient and family education
in Victoria, there is mandatory reporting of food allergies to the government in an attempt to reduce fatalities at schools, etc
consider desensitisation immunotherapy to develop tolerance
- eg. peanut oral immunotherapy
  - peanut allergy occurs in ~2% of children in Western countries
  - initial oral dosing with supervision, then using 30mg or 300mg maintenance doses generally develops tolerance to accidental exposures and the 30mg dose appears to be as effective with less side effects than the standard 300mg dose of peanut ²⁾

Ab + Ag (assoc. with or part of a cell/tissue) ⇒ complement activation
- ⇒ lytic action on cell memb. via complement/effector cell products
eg. Goodpasture's disease; Rh isoimmunisation disease of pregnancy; autoimmune haemolyticanaemia;
eg. myasthenia gravis (not lytic though only Ig bind Ach receptors)

Ab-Ag complexes in circulation in ratio 1-2:1 may cause deposition onto cell membranes activating complement
- ⇒ local inflammation including urticaria with joint effusions
eg. serum sickness (such as due to 1-2wks after taking cefaclor)
if Ab»Ag, then v.large complexes which are taken up by phagocytes & hence no serum sickness;

hapten on/in epidermis activates Langerhan's ⇒ LN T cells
- ⇒ local mainly epidermal inflammatory response
  - ⇒ spongiosis/blisters with initially lymphocytic infiltration & later macrophages;
eg. poison oak; nickel;

soluble transient hapten in dermis activates macrophages
- ⇒ dermal response ⇒ papule with monocytic infiltrate & some macrophages;

¹⁾

²⁾