Table 1 Indications of mucosal-related diseases

Adenoidal hypertrophy

URT

The enlarged adenoid may cause obstructions of nasal passages and eustachian tubes, persistent congestion, nasal drainage, sinusitis, otitis media;

Chronic infection (e.g., Streptococcus pyogenes) and allergy (e.g., house dust mites), acid reflux elicit lasting inflammation;

Abnormalities in the number and function of various lymphocyte subsets in the adenoid;

37,38,39

Herpangina

URT

A high fever and blister-like sores in the mouth and throat;

Infection of Coxsackievirus-A, Enterovirus-A and Echovirus;

Serotype-specific antibody response, macrophage proliferation and phagocytosis enhancement;

4041

Allergic rhinitis

URT

Nasal congestion, clear rhinorrhea, sneezing, postnasal drip, and nasal pruritis;

Common allergens including pollen, mould spores, house dust mites, and flakes of skin or droplets of urine or saliva from certain animals;

Th2 cell-induced IgE response, histamine secretion by mast cells, IL-4 and IL-13 facilitating the infiltration of eosinophils, T-lymphocytes, and basophils;

4243

Mucous membrane pemphigoid (one of autoimmune blistering disorders)

URT

Red, blistering lesions, ulceration, and subsequent scarring;

44

Seasonal influenza

URT/LRT

Fever, nonproductive cough, headache, muscle and joint pain, sore throat and a runny nose;

Infection of influenza A or B viruses;

Collaborative neutralization reactions of SIgA and IgG in LRT, induction of autonomous memory of alveolar macrophages;

4546

Respiratory syncytial virus infection

URT/LRT

rhinorrhea, nasal congestion, cough, sneezing, and bronchiolitis or even viral pneumonia;

Infection of respiratory syncytial virus;

IL-17-dominated immune response, neutrophilic inflammation;

4748

Pulmonary tuberculosis

LRT

Dyspnea, prolonged cough with mucus, pleuritic chest pain, hemoptysis;

Infection of Mycobacterium tuberculosis, macrophage aggregation induced granuloma formation to evade immune clearance;

Alveolar macrophages phagocytosis and production of cytokines such as TNF-α and IFN-γ, T-cell recruitment in granuloma;

4950

Pneumocystis pneumonia

LRT

Fever, nonproductive cough, dyspnea, and hypoxemia; with diffuse bilateral ground-

Infection of Pneumocystis; jirovecii in immunocompromised

Alveolar macrophage phagocytosis and production of IFN-γ, TNF-α, IL-1, IL-6; and GM-CSF, protective

5152

glass opacities on chest imaging;

patients (like HIV patients);

immune response of SIgM;

Pneumoconiosis

LRT

Long-term cough with mucus, shortness of breath and chest tightness, subpleural honeycombing and fibrosis;

Inhaled airborne dust and fibers induced macrophage dysfunction and interstitial lung disease;

Smaller particles take-up by alveolar macrophages phagocytosis, release of IL-1, TNF-α and lysosomal enzymes, generation of free radicals, and production of extracellular matrix and matrix metalloproteinases by activated fibroblasts;

53

Asthma

LRT

Dyspnea during eat, speak or sleep, wheezing, coughing especially at night or early morning, and chest tightness;

Chronic airway inflammation induced by factors like allergens, infections, obesity, smoking, systemic eosinophilia, leading to airway obstruction and hyperresponsiveness;

Production of thymic stromal lymphopoietin by DCs and injured epithelial cells eliciting Th2-cell type inflammation;

5455

Staph infections

URT/LRT/GIT

Antibiotic-associated diarrhea, bacteremia, toxic shock syndrome;

Infection of Staphylococcus aureus;

Junctional integrity alteration of enterocyte, infected epithelial cells eliciting Th2-cell immune response;

5657

Crohn’s disease

GIT

Abdominal pain and cramping typically in the lower right abdomen, diarrhea sometimes bloody, fistulas, weight loss, fatigue, fever and anemia, broad inflammation in the whole gastrointestinal tract;

Inflammatory bowel disease induced by multiple factors including genetic, environment, microbiota, overactive immune system;

Th1-cell immune response, high level of TNF-α and IL-12 induced autoimmune reaction; Th cell (e.g., Th17 and regulatory T cell) development hindrance because of microbiota dysbiosis, SIgA deficiency obstructing anti-inflammation reaction;

5859

Ulcerative colitis

GIT

Bloody diarrhea, abdominal pain and cramping, weight loss, fatigue, fever and anemia, limited inflammation in the colon and rectum;

Inflammatory bowel disease targeting the colon’s mucosa;

Th2-cell immune response, high level of IL-4 and IL-13, SIgA deficiency obstructing anti-inflammation reaction;

58,59,60

Helicobacter pylori infection

GIT

Chronic gastritis, peptic ulcers, dull or burning stomach pain (especially when you have an empty stomach)

Infection of Helicobacter pylori;

Th1-cell immune response, generation and activation of Th17 and regulatory T cells;

61

Celiac disease

GIT

Malabsorptio, diarrhea, fatigue, weight loss, bloating, anemia;

62

Rotavirus infection

Severe watery diarrhea, vomiting, fever, abdominal pain;

Infection of Rotavirus;

Th1-cell immune response, SIgA contributing to viruses shedding;

63

Cholera

Severe watery diarrhea, vomiting, thirst, leg cramps, restlessness and irritability;

Infection of Vibrio cholerae;

Increased mucosal-associated lymphocyte homing, protective immune response of SIgA;

6465