Question

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Vladimir, age 46 years, has had a persistent unproductive cough for several months that did not respond to cough medications. Recently, he has developed a productive cough accompanied by fatigue, anorexia, and night sweats. Examination in the ER indicated abnormal chest sounds and weight loss. A chest X-ray showed a small cavity and infiltrate. Discussion Questions 1.Discuss the pathologic changes occurring during the development of active tuberculosis at the cellular level.

Answer 1

Pathogenesis of active tuberculosis

Pathogenesis of active tuberculosis proceeds in steps from initial infection of macrophages to TH1 response that contain the bacteria and cause tissue damage

The following are the celular changes that occur during the active tuberculosis

entry to macrophages . Tuberculi bacilli entry the macrophages where the macrophages either kill the bacilli or get killed . The bacterial bacillus prevent the macrophages mediated cellular killing and destroy the macrophages . They do so by inhibiting the maturation of the phagosomes and block formation of phagolysosome which allow the bacteria to grow unchecked within the vesicle .

2) Activation of innate immunity

Multiple pathogens associated molecular pattern of m tuberculosis including lipoprotein and glycoprotein are recognised by the innate immunity which cause

The TH1 response , about 3 weeks after the infection a t helper 1 response is mounted that activate macrophage enabling them to become bactericidal . The response is initiated by the m bacilli entering the lymph nodes . The TH1 differentiation depend on interleukin 12 . This IL 12 is produced by antigen presenting cells which have encountered by the mycobacterium

3) bacteriocidal action of immune system

T cells synthesize interferon g (gamma) which produced nitrogen sunshade enzymes which further result in synthesize of NO NO2 HNO3 and free redical these components destruct the AFB ( acid fast bacillus )

4) epithelioid granuloma formation

Macrophages activated by Interferon gamma (INF-G) Changes to the epithelioid histocyctes that aggregate and form the granuloma .

Some of the the epithelioid cells fuse and form multinucleated gaint cells such as foreign body faint cells and langarhn type gaint cells .

The epithelioid cells are surrounded by the gaints cells which are surrounded by the lymphocytes cells and thus formation of granuloma occur .

The granuloma formed is called hard tubercle which with central caseous necrosis is known as soft tubercle

The activated macrophages also produces more TNF (tumor necrosis factors ) which further cause change of macrophages to the epithelioid cells . The importance of TNF is understood by the fact that the person who is treated with TNF anatgonist in rheumatoid arthritis cause reactivation of tuberculosis .

5) role of other immune cells

NKT cells also recognise mycobacterium antigen which are bound to CD1 cells of the t cells , this further cause release of INF -G (GAMMA )

The role of TH1 cells have the central role in this process

To summarize the process it is clear that immunity to m tuberculosis is primarily medicated by TH1 CELLS which stimulate macrophages to kill the bacterium

The formation of granulomatous inflammation is a characteristic feature of active tuberculosis

aint IL-I Cased -IFN TNF rhemokines mocro phage activatiom CH s bec

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