Mycoplasmal Pneumonia Pneumonia (MPP), also known as primary atypical pneumonia or cold agglutinin-positive pneumonia, is a common respiratory disease among children caused by infection with Mycoplasmal pneumoniae (MP), which frequently occurs in school-age children.
Mycoplasmal pneumonia pneumonia (MPP), also known as primary atypical pneumonia or cold agglutinin-positive pneumonia, is a common respiratory disease among children caused by the infection of Mycoplasmal pneumoniae (MP). It frequently occurs in school-age children. In the early stages, MPP is often overlooked in children, leading to delayed diagnosis and treatment. The "easy onset and rapid progression" of pediatric pneumonia often results in MPP developing rapidly into refractory Mycoplasmal pneumonia pneumonia (RMPP), which can even cause multiple organ dysfunction and significantly impact children's quality of life, especially their healthy development.
Mycoplasmal pneumonia often lacks specific symptoms in the early clinical stages, manifesting primarily as mild conditions such as generalized soreness and fatigue, which are often overlooked. However, as the disease progresses, it typically manifests as persistent and severe dry cough, high fever, accompanied by chest pain, sore throat, thick cough sputum, and headache. In severe cases, it can affect multiple organs, causing relatively severe conditions such as dyspnea, myocarditis, meningitis, and posing a threat to the patient's life. Currently, the pathogenesis of Mycoplasmal pneumonia is not fully understood, and the mainstream theories include direct contact damage and immune injury caused by Mycoplasma pneumoniae to host cells.
1. Direct Contact Damage of Mycoplasma Pneumoniae to Host Cells
Mycoplasma Pneumoniae is a pathogen that infects the respiratory system. Research using animal models and in vitro cell cultures has shown that after Mycoplasma Pneumoniae enters the respiratory tract, it attaches itself to respiratory epithelial cells. This adhesion process can damage the integrity of the respiratory mucosa epithelium, which is a prerequisite for Mycoplasma Pneumoniae pathogenicity. Mycoplasma Pneumoniae has a diverse array of adhesion proteins on its cell membrane surface, which not only possess antigenic properties but can also mutate to ensure close contact with host cells while avoiding elimination by the mucociliary system.
When Mycoplasma Pneumoniae combines with epithelial cells, it releases various cytotoxins at the attachment site, damaging the integrity of the airway mucosa. Additionally, the adhesion process consumes nutrients from epithelial cells, affecting cellular metabolism. Furthermore, the accumulation of hydrogen peroxide and superoxide radicals synthesized by Mycoplasma Pneumoniae within host cells becomes a significant pathogenic factor, inhibiting the ciliary motion of respiratory epithelial cells, causing mitochondrial swelling in epithelial cells, and ultimately leading to the dissolution and death of host cells.
2. Immune Injury Caused by Mycoplasma Pneumoniae Infection
① Humoral Immune Injury
After Mycoplasma Pneumoniae infection, the body produces specific antibodies such as immunoglobulin M (IgM) and immunoglobulin G (IgG), which are one of the important ways for the body to clear Mycoplasma Pneumoniae. IgM appears in the body about one week after infection with Mycoplasma Pneumoniae, reaching its highest concentration around three weeks and then gradually decreasing, lasting for 2 to 4 months. IgG appears about 20 days after the body is infected with Mycoplasma Pneumoniae, and a titer above 1:16 is considered clinically significant. Additionally, the more severe the illness, the higher the IgG positive rate. Individuals with congenital hypogammaglobulinemia are more susceptible to Mycoplasma Pneumoniae infection and complications such as nephritis and joint pain, indicating the importance of intact humoral immunity in preventing Mycoplasma Pneumoniae infection.
After Mycoplasma Pneumoniae infection, it induces the production of specific MP-IgE on the surface of respiratory mucosa, stimulating the production of inflammatory mediators such as serotonin and histamine, thereby activating the proliferation and activation of B lymphocytes to produce antibodies and promote recovery. However, the clearance capacity of B lymphocytes and specific antibodies is limited. Once the normal humoral immune response of the body abnormally intensifies, it can also cause repeated infections, resulting in pathological damage to corresponding tissues and leading to disease occurrence. Animal experiments have found that compared to normal mice, mice lacking B lymphocytes show more significant reductions in epithelial cell and vascular proliferation after Mycoplasma Pneumoniae infection, indicating that humoral immunity mediated by B lymphocytes and B1 lymphocytes is closely related to Mycoplasma Pneumoniae infection. Other studies have shown that injecting Mycoplasma Pneumoniae immune serum into B-lymphocyte-deficient mice can also lead to pathological airway wall vascular proliferation. This suggests that immune complexes on the airway surface are also one of the causes of chronic inflammation caused by Mycoplasma Pneumoniae.
After human infection with Mycoplasma Pneumoniae, it stimulates B lymphocytes to release IgM and IgG, but the host cell membrane and the cell membrane glycoantigens of Mycoplasma Pneumoniae have common antigenic components, which can lead to cross-reactivity and autoantibodies, forming immune complexes that cause target organ lesions, leading to various lesions in tissues or organs, and corresponding clinical symptoms. Mycoplasma Pneumoniae infection leads to significant consumption of complement. Studies have found that IgM and IgG levels in patients with Mycoplasma Pneumoniae pneumonia are significantly higher than in healthy patients. Therefore, humoral immunity is an important cause of Mycoplasma Pneumoniae pathogenicity.
② Cellular Immune Injury
Cellular immunity is primarily associated with T cells, which play a crucial role after Mycoplasma Pneumoniae infection. Animal experiments have found that animals with suppressed cellular immunity due to thymectomy exhibit less severe lung tissue damage after Mycoplasma Pneumoniae infection. Pathological studies during the early stages of infection revealed CD4+ T lymphocyte infiltration around arteries and bronchioles, indicating a lymphocyte-dominant immune response similar to an autoimmune reaction after Mycoplasma Pneumoniae infection.
T lymphocytes can be divided into multiple subsets, including CD8+ T lymphocytes and CD4+ T lymphocytes. CD8+ T lymphocytes can directly kill target antigens, while CD4+ T lymphocytes regulate the biological activity of other cells in the immune network to control the initiation, intensity, and other aspects of the immune response. Both are essential T lymphocytes. Under normal conditions, their levels maintain a dynamic balance, jointly regulating immune responses and homeostasis. However, under pathological conditions, CD4+/CD8+ imbalance can occur, leading to disease. Studies have shown that compared to healthy individuals, patients with Mycoplasma Pneumoniae pneumonia have significantly increased CD4+ levels and decreased CD8+ levels, and the more severe the illness, the more severe the imbalance. Children with Mycoplasma Pneumoniae pneumonia can damage their cellular immune function, leading to its disruption, indicating that Mycoplasma Pneumoniae protein antibodies may be the initiating factor for cellular immunity, and T lymphocytes play a crucial role in Mycoplasma Pneumoniae pneumonia.
③ Cytokines
After Mycoplasma Pneumoniae invades the lower respiratory tract, it stimulates respiratory epithelial cells, macrophages, and other cells to produce and release various cytokines such as IL-1β, IL-4, IL-6, IL-8, IL-18, and IFN-γ. These cytokines further chemoattract and activate specific and non-specific immune cells, triggering inflammatory reactions that participate in the pathogenesis of Mycoplasma Pneumoniae pneumonia, exacerbate the condition, and even damage the body's tissues, leading to hemophagocytic syndrome. IL-2 also plays a crucial role in the immune response of the body and participates in extensive regulatory functions. IL-6 is a pro-inflammatory cytokine induced by IL-1 and TNF-α, which promotes the differentiation of Th2 cells while inhibiting the differentiation of Th1 cells. TNF-α is another important pro-inflammatory cytokine involved in acute and chronic inflammatory responses. IL-10 is an anti-inflammatory cytokine secreted by TH2 cells that can target and inhibit the production of macrophage cytokines. Researchers believe that the combination of glucocorticoids and azithromycin in the treatment of Mycoplasma Pneumoniae lobar pneumonia in children results in a shorter time for clinical symptoms to disappear, faster X-ray absorption in the lungs, and faster recovery of inflammatory factors such as IL-6. IL-17 primarily promotes the production of cytokines that enhance intercellular adhesion molecule secretion function in stromal cells through the NF-kB-DNA pathway and MAP kinase pathways, promoting the secretion of large amounts of cytokines from bronchial epithelial cells, macrophages, and other cells to mediate immune inflammatory reactions.
Diagnosis of Mycoplasma Pneumoniae Pneumonia
Currently, there are no highly specific diagnostic methods for Mycoplasma Pneumoniae respiratory tract infections, whether from a pathogenic, biochemical, or radiological perspective. Therefore, the diagnosis of Mycoplasma Pneumoniae respiratory tract infection must be supported by microbiological results. Although the culture of Mycoplasma Pneumoniae has been optimized, it is still not a sensitive tool for detecting clinical specimens, and it is relatively expensive. Therefore, Mycoplasma Pneumoniae culture is rarely used as a clinical diagnostic method.
Clinically, commonly used diagnostic methods are serological tests, including cold agglutination test, passive particle agglutination method, gold immunodot assay, and enzyme-linked immunosorbent assay (ELISA). These methods are convenient and simple to operate, but serological diagnosis requires comparing samples from the acute phase and the recovery phase within 2-4 weeks to provide reliable diagnostic evidence. This is not conducive to determining the choice of antibiotics for children in the acute phase.
The application of molecular diagnostic methods (PCR) can provide rapid, sensitive, and specific results during the acute phase of infection to a certain extent. However, some studies have also shown that real-time polymerase chain reaction is not a definitive method for diagnosing symptomatic Mycoplasma Pneumoniae infection, and when PCR results are combined with serological data, the diagnostic accuracy does not improve.
In radiological imaging, there is a lack of specific imaging diagnosis in the early stage of Mycoplasma Pneumoniae pneumonia infection, and it is difficult to differentiate Mycoplasma Pneumoniae pneumonia from pneumonia caused by other pathogens solely through chest X-ray. However, chest CT examination can provide more diagnostic information compared to conventional chest X-rays. Studies have shown that CT values can be used to determine whether Mycoplasma Pneumoniae pneumonia is complicated with necrotizing pneumonia. However, it is necessary to strictly adhere to the indications and contraindications of lung CT.
References:
[1] Sun Meiting. Research progress on the pathogenesis, diagnosis and treatment of Mycoplasma Pneumoniae pneumonia [J]. Modern Diagnosis and Treatment, 2021, 32(09): 1370-1372.
[2] Zheng Xiaoxiao, Chen Jing. Research progress on the pathogenesis, diagnosis and treatment of Mycoplasma Pneumoniae pneumonia [J]. World Latest Medical Information Digest, 2021, (Issue 67).
[3] Wu Xue, Chen Xiao. Research progress on the pathogenesis, diagnosis and treatment of refractory Mycoplasma Pneumoniae pneumonia in children [J]. World Latest Medical Information Digest (Continuous Electronic Journal), 2022, (Issue 0).
About the Author
Xiaomichong, a researcher in drug quality, has long been committed to drug quality research and drug analysis method validation. Currently employed at a large domestic drug research and development company, engaged in drug inspection analysis and analysis method validation.
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