Cellular Hypersensitivity: An Overview

Introduction

Cellular hypersensitivity, also known as cell-mediated immunity, is an immunological response that completely depends on the activity of sensitized lymphocytes. The immune system plays an important role in defending against pathogens, but in some cases, it can overreact. This excessive reaction is caused by the immune system's interaction with antigens (allergens) and is called hypersensitivity.

Hypersensitivity reactions are classified into four types. The first three types of hypersensitivity reactions are considered immediate hypersensitivity reactions because they occur within 24 hours. The fourth type of hypersensitivity reaction is considered a delayed hypersensitivity reaction, as it occurs more than 12 hours after exposure to the allergen and has a maximum reaction time of 48 to 72 hours.

There are four types of hypersensitivity:

• Type I: Responses mediated by Immunoglobulin E (IgE) antibodies.

• Type II: Cytotoxic response mediated by Immunoglobulin G (IgG) or Immunoglobulin M (IgM) antibodies.

• Type III: Responses mediated by immune complexes.

• Type IV: Delayed response mediated by cellular reactions.

What Is Cellular Hypersensitivity?

Type IV hypersensitivity reaction, also known as cellular hypersensitivity, is mediated by T cells that induce inflammatory responses to exogenous or endogenous antigens. In certain circumstances, other cells, such as monocytes, eosinophils, and neutrophils, may also be involved. Antigen exposure triggers an early local immune and inflammatory response that attracts leukocytes. Type IV hypersensitivity reactions are a normal physiological phenomenon that helps fight infections, and dysfunction can lead to multiple opportunistic infections. These reactions can also cause adverse events if there is a harmful interaction between the immune system and the allergen. A classic example is exposure to poison ivy, which causes contact dermatitis. Some drugs (antibiotics, anticonvulsants) can cause type IV hypersensitivity reactions, leading to drug hypersensitivity and other clinical syndromes.

What Is the Mechanism of Cellular Immunity?

There are three subtypes of Type IV hypersensitivity:

• Contact dermatitis.

• Tuberculin-type hypersensitivity.

• Granulomatous-type hypersensitivity.

The pathophysiology of type 4 hypersensitivity varies depending on the underlying cause. The granulomatous disease occurs when the T cells are stimulated by antigen-presenting cells that cannot destroy the trapped antigen. The antigen-presenting cells then become giant multinucleated cells (large cells present at the site of inflammation), and many cytokines (signaling proteins that help control inflammation) are released to accomplish this, including interleukin-2 (IL-2) and tumor necrosis factors α and β.

In contact dermatitis, another mechanism occurs when an irritant or antigen is applied to the skin. This triggers an inflammatory response mediated by overexpression of ICAM-1, VCAM-1, and ELAM-1 (cell signaling molecules). Drug hypersensitivity occurs when various drug particles are neither metabolized by antigen-presenting cells nor presented by key molecules of the histocompatibility complex, yet bind to T-cell receptors.

• Contact Hypersensitivity - Contact hypersensitivity dermatitis occurs when haptens, which are considered exogenous antigens, enter the skin near epidermal and dermal cells and trigger an inflammatory response. Dermal dendritic and Langerhans cells play an important role in antigen presentation and sensitization of these haptens to CD4 and CD8 T cell lymphocytes (immune cells). Langerhans cells secrete cytokines and various other enzymes to call other immune cells to the site of hapten exposure. In addition, keratinocytes help recruit immune cells by secreting other groups of cytokines, such as IL-8. This causes the skin to become inflamed, swollen, itchy, and painful.

• Tuberculin-Type Hypersensitivity -Tuberculin-type hypersensitivity may be observed after intradermal injection of a purified protein derivative (PPD) called tuberculin (a product of Mycobacterium tuberculosis). This results in measurable local hardening and swelling. It is usually measured in millimeters 48 to 72 hours after injection.

• Granulomatous Hypersensitivity - It can occur in response to various antigens. Macrophages that have engulfed antigens are unable to destroy them and recruit more macrophages to replace those antigens. Collections of macrophages filled with intracellular antigens are called granulomas. An example of granulomatous hypersensitivity is sarcoidosis, a systemic granulomatous disease of unknown cause with variable clinical manifestations. Because the disease progresses slowly, sarcoidosis is sometimes called type 4 hyposensitivity.

What Are the Symptoms of Cellular Hypersensitivity Reaction?

The symptoms of cellular hypersensitivity reaction are listed below:

• Rash.

• Fever.

• Multiorgan involvement.

• Severe blistering.

• Pain.

• Sloughing of the epidermis resembling a third-degree burn.

• Generalized pustular rash.

• Sarcoidosis (autoimmune condition of tubercular origin).

How Is the Management or Treatment of Cellular Hypersensitivity Done?

Treatment of cellular hypersensitivity depends on the clinical condition produced by the reaction.

Listed below are some methods of management:

• Contact Dermatitis: Removal of the causative agent is the most important aspect of treating this condition. The severity of the skin condition determines the type of treatment, but topical steroids are most often used, and the strength of the steroid is adjusted according to the severity of the dermatitis.

• Steven-Johnson Syndrome or Toxic Epidermolysis: Aggressive life-saving therapy, including admission to the intensive care unit, optimal fluid therapy, antibiotics for secondary infections, and systemic corticosteroids, will be required.

• Granulomatous Disease - Treatment depends on the nature of the clinical condition. Steroid therapy is the standard of care for both systemic and ocular sarcoidosis. In addition to steroids, methotrexate has also been shown to be effective in pulmonary sarcoidosis. In Crohn's disease (inflammatory bowel disease), monoclonal antibodies against tumor necrosis factor (TNF) can be used as an effective means of treating the disease. Praziquantel can be used for schistosomiasis. Treatment should be started as soon as the tuberculin test comes positive. One of the most common treatments is the administration of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol.

What Are the Complications of Cellular Hypersensitivity?

The granulomatous disease can affect any organ in the body, but each type of granulomatous disease has common organs that are usually affected. For example, sarcoidosis (a tiny collection of inflammatory cells in various body parts) typically affects the lungs, eyes, and kidneys, causing pneumonia, pulmonary fibrosis, lung failure, cataracts, glaucoma, and kidney failure. Tuberculosis commonly affects the vertebrae and joints in addition to the lungs, causing back pain, stiff joints, and arthritis.

Contact dermatitis can cause auto eczema, a skin inflammation that develops systemically after her second exposure to a particular allergen. This skin inflammation destroys our body's most important barrier, the normal skin. Skin damage can lead to an increased risk of secondary skin infections from bacteria and other infectious organisms. Severe Steven-Johnson syndrome or toxic epidermal epidermolysis can cause permanent skin scarring.

Conclusion

Cellular hypersensitivity is a type IV hypersensitivity reaction or delayed hypersensitivity. Early recognition of the onset of Type IV hypersensitivity reactions helps optimal management of illness. Patients should be educated about the most common pathogens they are susceptible to and strategies for avoiding this infection. If a reaction occurs, removing the drug promptly and starting anti-inflammatory therapy may relieve symptoms and shorten the duration of the illness.