Animal TB Study Notes PDF

What is the pathogenesis of tuberculosis? 1) Transmission: a) TB is spread through the inhalation of airborne droplets containing M. tuberculosis that reaches to the alveoli of the lungs b) They will then be ingested by the alveolar macrophages 2) Immune Respon...

What is the pathogenesis of tuberculosis? 1) Transmission: a) TB is spread through the inhalation of airborne droplets containing M. tuberculosis that reaches to the alveoli of the lungs b) They will then be ingested by the alveolar macrophages 2) Immune Response: a) Immune defense is activated. Macrophages, T-cells, dendritic cells will be recruited to fight off the disease 3) Granuloma Formation: a) Host immune system forms granulomas to contain the infection. b) A granuloma consists of: A core of infected macrophages, surrounded by epithelioid cells, multinucleated giant cells, and lymphocytes, c) Granulomas can prevent bacterial spread but also provide a niche for dormant bacteria 4) Latent TB infection: a) If immune system effectively contains the infection, M. tuberculosis enters a latent state b) Latent TB is asymptomatic and non-contagious but can be reactivate under immunosuppressed conditions 5) Active TB Disease: a) In some individuals, granulomas may break down, releasing the bacilli into the airways and bloodstream b) Leading to widespread tissue damage, cavity formation in the lungs, and systemic symptoms like fever, night sweats, and weight loss. 6) Extrapulmonary TB: a) TB can spread to other organs via the lymphatic system or bloodstream, leading to extrapulmonary TB 7) Pathological Changes: a) Caseous necrosis is a hallmark of TB What are the characteristics of models for TB? 1) Experimental infection mimics natural disease 2) Infection results from low-dose challenge 3) Route of exposure simulates natural exposure 4) Pathology present in relevant target organs 5) Lesions analogous to those found in naturally infected host 6) Spectrum of disease equivalent to that in the naturally susceptible host Why did murine, rabbit, and guinea pig models have emerged as the forefront of TB research? 1) Infection can occur with inhalation 2) Animals manifest an innate and acquired immune response 3) Animals often initially control bacillary growth in the lung 4) They ultimately succumb to the disease Discuss on how mouse models are used as a model of TB. - Development: tail vein & aerosol - Benefits: Easy to maintain; affordable; high-yield means to study vaccines; anti-TB drugs; immune mechanisms; host genetics - Limitations: Development of resistance for classic TB disease (non-respondent to therapy) - Applications: Good for studying the immunology of mycobacterial infections Discuss on how guinea pig are used as a TB model. - Development: Aerosol, subcutaneous - Benefits: exceptional susceptibility to infection with a few inhaled mycobacteria; can be used as models in various forms of TB infection such as childhood TB and TB in immunosuppressed hosts  - Limitations: Limited availability of immunologic reagents for studying guinea pig host immune responses - Applications: Evaluation on the safety and efficacy of vaccines or immunity strategies Discuss on how rabbit are used as a TB model. - Development: Spinal punching, aerosol - Benefits: Easy to form cavitation; Rabbit spinal TB was the best model to research - Limitations: Lack of relevant immune reagent - Applications: Good for TB transmission research; preferred models on diagnosis & treatment of cavitary, spinal, and joint TB Discuss on how non-human primate are used as a TB model. - Development: via bronchoscope - Benefits: can mimic a variety of clinical manifestations, and pathological characteristics - Limitations: Transgenic monkeys difficult to obtain; limited availability of immune reagent; High variations; High cost & space requirements - Applications: Evaluation of individualized anti-TB drugs and vaccines, treatment strategy