Pathogenesis (development of disease)
The causative agents of tuberculosis belong to the Mycobacterium tuberculosis complex. These include M. africanum, M. microti, M. tuberculosis, and M. canetti. The pathogens are transmitted via aerosols. Uptake of the pathogens occurs in the alveoli (pulmonary alveoli) via macrophages (phagocytes). This is followed by either lysis (dissolution) of the pathogens or the bacteria lyse the macrophages and enter the bloodstream via monocytes (cells of the immune system that are precursors of macrophages), from where they settle primarily in the lungs, but also in the lymph nodes. After a few weeks, a type 4 hypersensitivity reaction against the pathogen occurs with subsequent tissue destruction. Subsequently, immunological processes lead to the formation of tuberculomas (tuberculous round), which have central necrosis (cell death). Even at this stage, the infection can still heal; this usually occurs in the lymph nodes, and mycobacteria often survive in the lungs.
Etiology (causes)
Biographic causes
- Genetic burden
- Genetic risk depending on gene polymorphisms:
- Genes/SNPs (single nucleotide polymorphism):
- Genes: TYK2 – Mutations in the TYK2 gene can decrease the activity of the enzyme tyrosine kinase 2, which has the following effects: signals from interleukins 12 and 23 in T helper cells are transmitted in a diminished manner due to reduced levels of tyrosine kinase 2, resulting in reduced production of interferon gamma (interferon-γ); people homozygous for the P1104A gene variant are thus at increased risk of developing tuberculosis after contact with mycobacteria.
- SNP: rs34536443 (P1104A) in the TYK2 gene.
- Allele constellation: CG (prevalence: 42/1,000) carrier of a tuberculosis susceptibility mutation/mutation that renders susceptible to certain diseases (here: tuberculosis) (prevalence/disease frequency: 42/1,000).
- Allele constellation: CC (prevalence: 1.7/1,000).
- Genes/SNPs (single nucleotide polymorphism):
- Genetic risk depending on gene polymorphisms:
- Socioeconomic factors
- Local residents from socially disadvantaged groups
- People from third world countries
- Prison inmates
Behavioral causes
- Consumption of stimulants
- Tobacco (smoking)
- Drug use (intravenous, i.e., through the vein).
Causes related to disease
- Diabetes mellitus
- HIV infection (predominant risk factor worldwide).
- Immunocompromised persons
- Malnutrition
- Individuals with inadequately treated tuberculosis.
Medication
- Immunosuppressants (drugs that suppress the immune system) – ciclosporin (INN), also cyclosporin A; leflunomide.
- TNF-alpha inhibitors
- Cytostatics (substances that inhibit cell growth or cell division) – including methotrexate.
X-rays
- Radiatio (radiation therapy) for tumor diseases leads to a weakening of the immune system
Surgeries
- After major surgery, there is often a weakening of the immune system
Environmental stress – intoxications (poisonings).
- Quartz dust (dusts containing crystalline silica (SiO2), silicosis → silico-tuberculosis).
Other causes
- People with close contact with affected people
