Q. Are the caseating granulomas seen in tuberculosis considered part of innate or adaptive immunity? What’s happening inside them?
A. Caseating granulomas are a part of adaptive immunity. Having said that, innate immune cells (macrophages) are heavily involved. There are several steps in the process of granuloma formation in tuberculosis:
1. Initially, M. tuberculosis infections are unable to be stopped by neutrophils. So, macrophages are called in.
2. Some of the macrophages become activated because of the local production of interferon (primarily IFN-alpha from the macrophages and IFN-beta from lung tissue cells). The IFN-activated macrophages have some limited ability to kill and digest M. tuberculosis organisms.
3. The activated macrophages produce cytokines that draw helper T cells to the area. Since the activated macrophages can have a limited effect on controlling M. tuberculosis and can degrade some of the bacterial cells, they can present the M. tuberculosis antigens on their surface in association with HLA Class II antigens.
4. Helper T cells that recognize M. tuberculosis antigens are activated by the combination of antigen presentation and cytokine production (predominantly, IL-1 and IL-12). The combination of IL-1 and IL-12 activate the helper T cells to become activated Th1 cells.
5. The activated Th1 cells produce IFN-gamma which highly activates macrophages. These highly activated macrophages are able to, in most individuals, kill the M. tuberculosis bacteria.
6. A granuloma forms, with M.tuberculosis in the center, either as free organisms or as macrophage-ingested organisms, depending upon how good the individual’s highly activated macrophages are at killing M. tuberculosis bacteria. The highly activated macrophages are surrounded by activated Th1 cells that keep producing IFN-gamma as the macrophages keep presenting M. tuberculosis antigens. The IFN-gamma in turn keeps the macrophages highly activated, allowing them to continue to kill M. tuberculosis and to continue to present antigens. The Th1 cells are in turn surrounded by additional macrophages that differentiate to become fibroblast-like cells, forming the granuloma.
7. One can view this granuloma as maintaining a balance between the ability of the highly activated macrophages to kill M. tuberculosis organisms as rapidly as they divide and the ability of the M. tuberculosis organisms to kill the macrophages.
If the M. tuberculosis organisms gain the upper hand (perhaps due to immunosuppression that might occur for a variety of reasons), the M. tuberculosis organisms kill the macrophages, causing more and more macrophages to come into the area. The dead and dying macrophages form the caseated material. If the M. tuberculosis organisms replicate sufficiently to break out of the granuloma or prevent the formation of the granuloma in the first place, the activated and highly activated macrophages release their cytokines into the milieu of the lung tissue, rather than into the granuloma. Among the cytokines produced in large amount by highly activated macrophages is tumor necrosis factor (TNF). TNF can kill lung tissue cells, resulting in a kind of accidental “scorched earth” policy. The damage caused results in cavitation in the lung.
- Kristine said Thanks, Meghan – I agree! It should be a primary concern, not an afterthought, and we need to...
- Meghan J said Thank you for this post. It’s a topic that is often added as an afterthought to medical schoo...
- Kristine said Thanks, Sumayya!
- sumayya roohi said mantle cell lymphoma is CD 5+.CD 23-, CD 79b+, FMC7 and cyclin D1 +
- Kristine said I would presume so – at least as long as it remained in the blood.
- Kristine said “Open” chromatin means that you can see through the chromatin – it appears fine, l...
- Kristine said Thanks, Julia!! So glad you found it and it was helpful
- mcray aboagye said Thanks
- ikondere julius said thanx so much
- Kristine said No – I’m sorry, we’re all sold out.
- Rachel Nicholson said Are these shirts still available?
- Amanulla said And Macrocyte + Hypersegmented neutrophil=Megaloblastic anemia