HYPERSENSITIVITY REACTIONS
HYPERSENSITIVITY REACTIONS
The immune system protects the body from damage by fighting off invasive substances and infections. However, sometimes the immune system creates unwanted reactions by classifying harmless substances as harmful. This is called a hypersensitivity reaction. (1)
Hypersensitivity reactions or hypersensitivity responses (HR) are exaggerated or inappropriate immune responses to an antigen or allergen. (2)
Hypersensitivity reactions have been grouped into four types based on their mechanism, this is known as the Gell and Coombs classification. Some evidence suggests a potential fifth type, but this may be a subset of type 2 hypersensitivity reactions.
· Type I: reaction mediated by IgE antibodies
· Type II: cytotoxic reaction mediated by IgG or IgM antibodies
· Type III: reaction mediated by immune complexes
· Type IV: delayed reaction mediated by cellular response (3)
Type I Hypersensitivity:
Type I hypersensitivities include atopic diseases involving an exaggerated IgE-mediated immune response (e.g., allergic asthma, rhinitis, conjunctivitis, and dermatitis) and allergic diseases involving immune responses to foreign allergens (e.g., anaphylaxis, urticaria, angioedema, food and drug allergies). The allergens that lead to type I hypersensitivity can be harmless (e.g. pollen, mites, food, drugs, etc.) or more dangerous, such as insect venoms. The reaction can manifest itself in different areas of the body and can lead to the following manifestations: (4)
· Allergic rhinitis in the nose or hay fever
· Allergic conjunctivitis in the eye, possibly due to seasonal allergens such as pollen or mold spores
· Dermatologic hives, atopic eczema or erythema
- Soft tissue angioedema
- Pulmonary reactions, such as allergic asthma or hypoxia
- Systemic reaction, which is a life-threatening medical emergency, and also known as anaphylaxis.
Clinically Anaphylactic Reaction may be:
- Localized reaction.
- Systemic reaction.
- Localized Reaction:
- It causes skin allergies (wheel), Hay fever, allergic rhinitis, asthma, atopic conjunctivitis, and urticaria.
Clinical Relevance - Anaphylaxis
Anaphylaxis is a systemic response to an antigen, leading to bronchoconstriction and vasodilation. This decline in oxygen transportation and can lead to anaphylactic shock and possibly death. It is usually treated with adrenaline, to dilate the bronchioles and constrict the blood vessels, antihistamines, to reduce the inflammatory effects of histamine, and corticosteroids, to reduce systemic inflammation.
- Systemic Anaphylactic Reaction:
- It is a generalized phenomenon and leads to:-
- Pallor, Nausea, vomiting, asthma, laryngeal edema, and Hoarseness.
- Abdominal pain, diarrhea, low blood pressure, and ultimately patient goes into shock (anaphylactic shock).
Flow chart showing the pathophysiology of type I hypersensitivity reactions(5)
Type II Hypersensitivity Reactions
Type II hypersensitivity reaction refers to an antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens, resulting in cellular destruction, functional loss, or tissue damage. Damage can occur via three different mechanisms:
1. Antibody binding to cell surface receptors and altering its activity
2. Activation of the complement pathway
3. Antibody dependant cellular cytotoxicity
The type II hypersensitivity reaction develops in response to cell surface modifications or matrix-associated antigens generating antigenic epitopes that are regarded as foreign by the immune system. The most common causes include medications like penicillin, thiazides, cephalosporins, and methyldopa. The drug molecule either binds to the surface of cells resulting in a neoantigen or alters the epitopes of the existing self-antigen on the cell surface. This directs the immune system to recognize modified antigens as foreign, with the breakdown of the immune tolerance and the production of antibodies directed to self-antigens.(6)
Type III Hypersensitivity
In type III hypersensitivity reactions, an abnormal immune response is mediated by the formation of antigen-antibody aggregates called "immune complexes." They can precipitate in various tissues such as skin, joints, vessels, or glomeruli and trigger the classical complement pathway. Complement activation leads to the recruitment of inflammatory cells (monocytes and neutrophils) that release lysosomal enzymes and free radicals at the site of immune complexes, causing tissue damage.
The most common diseases involving a type III hypersensitivity reaction are serum sickness, post-streptococcal glomerulonephritis, systemic lupus erythematosus, farmers' lung (hypersensitivity pneumonitis), and rheumatoid arthritis. The principle feature that separates type III reactions from other hypersensitivity reactions is that in type III reactions, the antigen-antibody complexes are pre-formed in the circulation before their deposition in tissues. (7)
Type IV Hypersensitivity
A Type IV hypersensitivity reaction is mediated by T cells that provoke an inflammatory reaction against exogenous or endogenous antigens. In certain situations, other cells, such as monocytes, eosinophils, and neutrophils, can be involved. After antigen exposure, an initial local immune and inflammatory response occurs that attracts leukocytes. The antigen engulfed by the macrophages and monocytes is presented to T cells, which then becomes sensitized and activated. These cells then release cytokines and chemokines, which can cause tissue damage and may result in illnesses. Examples of illnesses resulting from type IV hypersensitivity reactions include contact dermatitis and drug hypersensitivity. Type IV reactions are further subdivided into type IVa, IVb, IVc, and IVd based on the type of T cell (CD4 T-helper type 1 and type 2 cells) involved and the cytokines/chemokines produced.
Delayed hypersensitivity plays a crucial role in our body's ability to fight various intracellular pathogens such as mycobacteria and fungi. They also play a principal role in tumor immunity and transplant rejection. Since patients with acquired immunodeficiency syndrome (AIDS) have a progressive decline in the number of CD4 cells, they also have a defective type four hypersensitivity reaction. (8)
REFERENCES
1) https://www.medicalnewstoday.com/articles/hypersensitivity-reactions
3) https://www.ncbi.nlm.nih.gov/books/NBK562228/
5) https://en.wikipedia.org/wiki/Type_I_hypersensitivity
7) https://www.ncbi.nlm.nih.gov/books/NBK559122/
