Hypersensitivity: Type 1, 2, 3 and 4, Causes and Treatments

It is described as an enormous, undesirable, and damaging reaction that produces discomfort, usually caused by the immune system.

This reaction requires a pre-sensitized (immune) state of the host so that the following can be classified: type 1, type 2, type 3, and type 4, depending on the mechanisms involved and the time required for the reaction.

With periodicity, a particular clinical condition (disease) may involve more than one type of resistance, then each of the types associated with this condition is detailed:

Type 1 hypersensitivity

Hypersensitivity type 1 is also known as immediate or anaphylactic Hypersensitivity.

Therefore, it can include skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma), and gastrointestinal tract (gastroenteritis).

Next, it can cause various symptoms due to minor inconveniences to death.

It usually takes 15 to 30 minutes from exposure to the antigen, although it may have a delayed onset (10 to 12 hours).


Immediate Hypersensitivity is intervened by Immunoglobulin E (IgE). The main cellular component in this Hypersensitivity is the Mastocito or Basófilo.

The reaction is extended or varied because of Platelets, Neutrophils, and Eosinophils since a study of the reaction site shows especially Mast cells and Eosinophils.

The resistance component involves the preferential obtaining of Immunoglobulin E (IgE) in response to specific allergens or antigens.

The specific component of why some people are more prone to Type 1 hypersensitivity is unclear.

However, it has been shown that such individuals preferentially produce more lymphocytes or TH2 cells, which favors the change of class to Immunoglobulin E (IgE).

Subsequent exposure to the same allergen crosses Immunoglobulin E (IgE), bound to the cell, and triggers the release of various pharmacologically active substances.

With the Fragment Receptors (RFC), the cross-linking of the Immunoglobulin E receptor (IgE) with the Fragment Receptors (RFC) precipitate the Mastocytes.

The degranulation of the Mastocytes is preceded by an increase in the influx of serum calcium (Ca +2), which is vital in the course; the ionophores that increase serum calcium (Ca +2), cytoplasmic also promote degranulation.

That is, said reaction process is amplified by the PAF (Platelet Activating Factor) that causes the aggregation of platelets and the release of Histamine, Heparin, and active Vase Amines, among others.

Eosinophils can also control the local reaction by releasing Arylsulfatase, Histaminase, Phospholipase-D, and Prostaglandin-E, although this role of Eosinophils is now in question.

Cyclic nucleotides appear to play a significant role in modulating the immediate hypersensitivity reaction, although their exact function is unknown.

Substances that alter levels of cyclic monophosphate adenosine (cAMP), and cyclic monophosphate guanosine (GMF), significantly alter allergic symptoms.

Therefore, substances that increase cyclic monophosphate adenosine (cAMP), intracellular, seem to relieve allergic symptoms, particularly bronchopulmonary, and are used therapeutically.

Conversely, agents that decrease cyclic monophosphate adenosine (cAMP), or stimulate cyclic monophosphate guanosine (GMF), aggravate these allergic conditions.

Diagnostic tests for immediate Hypersensitivity include skin tests (by puncture and intradermal), measurement of total Immunoglobulin E (IgE) and Immunoglobulin E (IgE) antibodies, specific against suspected allergens.

These are measured by a modification of the Enzyme-Linked Immunosorbent Assay.

The increase in Immunoglobulin E (IgE) levels is indicative of an atopic condition, although this may be elevated in some non-atopic diseases (e.g., myelomas, helminth infection, etc.).

Symptomatic treatment is achieved with antihistamines that block the histamine receptors.

Carolina Sódica inhibits the degranulation of mast cells, probably by inhibiting the influx of serum calcium (Ca ++).

Late-onset allergic symptoms, particularly leukotriene-mediated bronchoconstriction, are treated with leukotriene receptor blockers or cyclooxygenase inhibitors.

The symptomatic relief, although short-term, of bronchoconstriction is provided by bronchodilators (inhalants) such as Isoproterenol derivatives (Terbutaline, Albuterol).

Tofilina increases cyclic monophosphate adenosine (cAMP), inhibiting cyclic monophosphate adenosine (cAMP) phosphodiesterase and inhibits the intracellular release of serum calcium (Ca ++); it is also used to relieve bronchopulmonary symptoms.

The use of antibodies or Immunoglobulin G (IgG) against the Fragment Receptor portions (RFC) of Immunoglobulin E (IgE), which binds to the Mastocytes, has been approved for the treatment of specific allergies since it can block the sensitization of the Mastocitos.

Hyposensitization (Immunotherapy or Desensitization) is another treatment modality that is successful in several allergies, particularly in insect venoms and pollen to a certain extent.

The mechanism is unclear, but there is a correlation between the appearance of Immunoglobulin G Blockers (IgG) antibodies and the relief of symptoms.

Type 2 Hypersensitivity

Type 2 Hypersensitivity, also known as Cytotoxic Hypersensitivity, is detrimental to various organs and tissues.

Antigens usually are endogenous. However, exogenous chemical derivatives (also known as Haptens) can bind significantly to cell membranes, drastically leading to Type 2 Hypersensitivity.

Drug-induced hemolytic anemia, granulocytopenia, and thrombocytopenia are examples of this type.

The reluctance is from minutes to hours since Type 2 Hypersensitivity is mainly involved by antibodies of the classes Immunoglobulin M (IgM) or Immunoglobulin G (IgG) and its complements.

Phagocytes and K cells play a crucial role in this process.

The lesion has antibodies, supplements, and neutrophils.

Diagnostic biopsies contain the location of circulating antibodies against the tissues involved and the representation of antibodies and complement in the study (biopsy) using immunofluorescence.

The treatment includes anti-inflammatory and immunosuppressive agents.

Type 3 hypersensitivity

Type 3 Hypersensitivity is also known as Hypersensitivity to immune complexes, including:

  • General reaction
  • Skin: Systemic Lupus Erythematosus, Arthus reaction.
  • Kidneys: Lupus Nephritis.
  • Lungs: Aspergillosis.
  • Blood vessels: Polyarteritis.
  • Joints: Rheumatoid Arthritis.

This resistance can be the pathogenic component of the diseases caused by many microorganisms.

Also, it develops from 3 to 10 hours after the antigen display (for example, the Arthus reaction).

Soluble immune complexes mediate it. In their totality, they are of the class of Immunoglobulin G (IgG), although the I Immunoglobulin M (IgM) may also be involved.

The antigen becomes exogenous (chronic bacterial, viral, or parasitic infections) or endogenous autoimmune (non-organ specific: for example, Lupus).

The antigen is feasible and lacks binding to the organ involved. The primary components are soluble immune complexes and complement the Anafilotoxins (C3a, 4a, and 5a).

The damage is caused by platelets and neutrophils, leading to immune complexes’ deposits.

Macrophages that infiltrate later stages may be involved in the healing process. The antibody’s affinity and the immune complexes’ size are essential in the production of the disease and the determination of the tissue involved.

Diagnosis involves an examination of tissue biopsies to detect immunoglobulin and complement deposits by immunofluorescence microscopy.

Immunofluorescent staining in Type 3 hypersensitivity is granular (as opposed to linear in type 3, as seen in Goodpasture syndrome).

The presence of immune complexes in serum and depletion at the complement level is also diagnostic.

The binding of turbidity (Nephelometry) mediated by polyethylene glycol of C1q (also known as antibodies) and the test of Raji cells are used to detect immune complexes.

The treatment includes anti-inflammatory agents.

Type 4 hypersensitivity

Type 4 hypersensitivity, also known as Mediated or Delayed-Type Hypersensitivity, is involved in numerous autoimmune and infectious diseases such as Tuberculosis, Leprosy, Blastomycosis, Histoplasmosis, Toxoplasmosis, and Leishmaniasis, among others.

On the other hand, granulomas appear due to infections and foreign antigens since delayed Hypersensitivity causes contact swelling by chemical agents, metals, and various cutaneous reactions.

Type 4 hypersensitivity develops processes that link T lymphocytes, monocytes, and macrophages.

Likewise, cytotoxic T cells (Tc) cause natural affections. In contrast, the T (TH1) collaborating cells absorb cytokines that drive cytotoxic T cells, recruiting and activating Monocytes and Macrophages, which have greater responsibility in this process.

The classic example of this Hypersensitivity is the tuberculin reaction (Montoux) that reaches its peak 48 hours after the injection of the antigen derived from the purified tuberculin protein (PPT). The lesion is characterized by induration and erythema.

Hypersensitivity IV lesions contain essentially monocytes and some cytotoxic cells (lymphokines) involved in the resistance of hypersensitivity IV, including the chemotactic factor of monocytes, interleukin-2, interferon-gamma, tumor necrosis factor (TNF) alpha/beta, etc.

In vivo, diagnostic tests contain delayed cutaneous resistance, for example, the Montoux test and patch test (for dermatitis by agents exposed to contact).

The tests or biopsies for delayed Hypersensitivity include mitogenic response, lympho-cytotoxicity, manufacture of corticosteroids, and different immunosuppressive agents used in the procedure.