Introduction:
Immune-mediated lung injury is caused by a complex group of diseases that results in infiltration of the lungs with inflammatory cells that leads to progressive airway remodeling and parenchymal (numerous thin-walled alveoli of the lungs) lung injury. Exposure to certain antigens results in immune reactions, eventually leading to lung injury. The injury's severity depends on the antigen type, patient susceptibility, and the type of immune response initiated.
The progression of the disease is prevented by early identification, removal of the inciting antigen, and intervention with steroid medications. In this article, we will see more about the injurious effects of certain antigens on the lungs.
How does the Respiratory System Respond to Antigens?
The human airways and respiratory system are constantly exposed to antigens eliminated by the host immune system. Initially, when the antigens enter the upper airway, the mechanical barrier comes into action. It is the first line of defense, where particles greater than five micrometers are trapped by the nasal hair, pharyngeal (area posterior to the nasal cavity) mucosa, and the mucin are cleared by ciliary (hair-like projections that trap the foreign particle and move them out of the body) action.
All those antigens that escape the mechanical barrier reach the lower airways, where they are acted upon by the innate (immunity present by birth and the first one to encounter a foreign body) pulmonary immune response. It is a complex orchestration of different immune cells like
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Leukocytes: White blood cells involved in the body's defense mechanism.
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Phagocytic Alveolar Macrophages: Scavengers that kill microbes and foreign bodies. They are large phagocytic cells that swallow the antigens.
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Fibroblasts: Contributes to the formation of connective tissues.
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Epithelial Cells: Produces antimicrobial factors.
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Pneumocytes: Cells found on the surface of alveoli (air sacs in lungs).
The immune cells get activated by antigens and secrete enzymes and antibodies. Fibronectin, lactoferrin, and defensins which has natural antimicrobial properties and produce crucial immune responses. The lymphatic system helps eliminate pathogens by clearing debris, fluid, and white cells. Some individuals are genetically susceptible to developing a hyperactive immune response when activated by an antigen, this phenomenon is known as a hypersensitive reaction (hypersensitivity). In such individuals, a diverse group of pathogens will initiate an adverse immune reaction characterized by the inflammatory cellular infiltration of the lungs that progressively remodels the airway and causes lung injury.
What is the Mechanism of Immune-Mediated Lung Injury?
When a viral pathogen enters the body, the immune mechanism of the body gets activated for the coordination of complex events resulting in the infiltration of lungs with inflammatory cells that results in injury in the airways and the lung parenchyma involving the alveoli (air sacs). Microscopically, the injury is manifested as loss of alveolar epithelial cells, hemorrhage (loss of blood from damaged blood vessels), hyaline (composed of necrotic debris), membrane formation, edema, and inflammation. This phenomenon is known as diffuse alveolar damage and is not specific to an antigen but is associated with several respiratory disease conditions and insults like
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Influenza virus infection: A viral infection that affects the lungs, throat, and nose.
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Hantavirus infection: A severe pulmonary viral infection. Rodents are the carrier.
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Bird flu: A viral infection that infects birds and humans.
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Severe acute respiratory syndrome (SARS): A contagious and fatal viral infection.
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Endotoxic shock: Widespread infection in the body causing organ failure and dangerously low blood pressure.
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Chemical and drug-induced lung injury: Exposure to certain drugs and chemicals cause inflammation and fibrosis of the lungs.
What is the Role of T-Cells in Immune-Mediated Lung Injury?
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T cells play a crucial role in eliminating viral antigens from the lungs. Subpopulations of T cells employ different mechanisms for eradicating the virus. For example, the CD8 T cells (effector T cells) provide complete protection against the influenza virus compared to CD4 T cells. The same T cells mediate the damaging process of the lungs. The extent of lung injury depends on the magnitude of antigen load. With low antigen load, the CD8 effector T cells block the viral replication with their lower concentration and do not cause any illness or damage to the lungs. In contrast, when the antigen load increases, the quantity of CD8 effector T cells also increases, exacerbating lung injury; this has been shown in influenza virus infection and respiratory syncytial virus infection (a common respiratory virus causing symptoms similar to cold).
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The extent, location, and type of lung injury caused by different subpopulations of T cells are also different. CD4 T cells are observed to cause no detrimental effect on lung alveoli and gas exchange and provide protection against the influenza viral antigen compared to the protective and damaging effect caused by CD8 T cells. Thus it is inferred that antigen clearance is achieved without significant lung injury.
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The presence of viral antigens will trigger the T cells to clear the antigen and activate immune mechanisms. The primary mediator of the immune mechanisms is TNF (tissue necrosis factor) which also plays a role in the clearance of antigens. Lung injury mainly occurs by activating epithelial chemokine expression (stimulating the migration of the immune white blood cells to the site of antigens), which results in infiltration of the lungs by the host inflammatory cells.
What Controls the Extent of Immune-Mediated Lung Injury?
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From the above discussions, it is clear that an effective response against an antigen is accompanied by an adverse inflammatory reaction, damaging the lungs, which may negatively affect their functioning. Therefore, the weakening of the immune response is critical for maintaining the functional integrity of the lungs. Limited evidence supports the role of immunoregulatory cells that protect the lungs from the detrimental effect of T cell activities.
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The role of regulatory CD4 T cells has been the most broadly studied of all the immunoregulatory mechanisms. CD4 regulatory T cells are subdivided into natural and inducible regulatory T cells, with several mechanisms for controlling the immune response. The presence of regulatory T cells will limit the inflammatory process without compromising the elimination of antigens.
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In addition to the regulatory cells, natural killer T cells exhibit immunomodulatory (suppress the immune system) functions.
Conclusion:
A complex array of factors are involved in the clearance of an antigen from the lungs. This mechanism may damage the tissue of the lung, resulting in a physiological impairment. Some studies suggest that immunosuppressive drugs can be administered for highly virulent antigens, which will buy time for the antiviral drugs to act and delay the immune-mediated damage to the lungs. However, adverse effects are higher for this intervention, and a need for a more conservative approach is raised.
