Question

explain the development of necrosis in tuberculosis in detail (use words, macrophage, mycobacterium, mycelia acid, phagocytosis, granuloma, caseous)

Answer 1

Pathogenesis of Mycobacterium tuberculosis:

• The cell wall of Mycobacterium tuberculosis has mycolic acid. The mycolic acid biosynthesis is essential for the survival of bacteria inside the host macrophage cells. Mycolic acid prevents the attack of oxygen radicals, cationic proteins, lysozymes in the phagocytic granule.
• Phagocytosis by macrophages: Macrophages and monocytes engulf the antigen and try to destroy it. Since the antigen is poorly degradable, these cells fail to digest and degrade the antigen and instead undergo morphologic changes.
• CD4+ T cells: Macrophages, being antigen-presenting cells, having failed to deal with the antigen, present it to CD4+ T lymphocytes. These lymphocytes get activated and produce lymphokines (IL-1, IL-2, interferons, TNF-alpha).

• Various cytokines formed by activated CD4+ T cells and also by activated macrophages to perform the following roles:

i) IL-1 and IL-2 stimulate proliferation of more T cells.
ii) Interferons activates the macrophage.
iii) TNF-alpha promotes fibroblast proliferation and activates endothelium to secrete prostaglandins to induce inflammation.
iv) Growth factors (transforming growth factor-beta, platelet-derived growth factor) stimulate fibroblast growth.

A granuloma is formed of macrophages modified as epithelioid cells in the center, with some interspersed multinucleated giant cells, surrounded peripherally by lymphocytes (mainly T cells), and healing by fibroblasts or collagen depending upon the age of granuloma.

Host immune response:

Macrophages present the mycobacterial antigens to T helper cells and activate them T-helper 1, 2 subsets.

The activated macrophages aggregate around the center of the lesion to form the granuloma called tubercle. Tubercles are the pathological feature of tuberculosis.

There are two types of tubercles:

• Soft tubercles
• Hard tubercles

Hard tubercle is initially hard and they are composed of the central zone of epithelioid and giant cells and the peripheral zone of lymphocytes and fibroblasts.

Soft tubercle - the central part of tubercle undergo caseous necrosis later.