Introduction:
Tuberculosis is a deadly respiratory infection caused by Mycobacterium tuberculosis. One of the top ten causes of death in 2017. Every year ten million people are affected by tuberculosis (TB) and fall sick. About 10 percent of this occurs in children, and 1.5 million registered fatalities. Despite several measures implemented to prevent and cure the disease, the mortality rate makes it one of the world's top infectious killers.
Once the mycobacterium tuberculosis (M. tuberculosis) bacteria enters the body, it triggers a complex chain of immune responses. The immune response may result in latent infection, active tuberculosis, or the wiping out of pathogens from the body. CD4 (a glycoprotein that acts as a coreceptor of the T-Cell receptor) + T-lymphocytes and granuloma formation were believed to be the most important defense mechanism against Mycobacterium tuberculosis. However, further studies have indicated that every single immune system component raises in defense against this pathogen.
There is enough evidence to suggest the importance of CD4 + T-cells in controlling the spread of infection, but the importance of CD8 + T-cells in humans is yet to be proven. Research in animal models suggests that CD8 + T-cells have a crucial and complex role in controlling tuberculosis. Mycobacterium Tuberculosis infection in humans will have two types of CD8 + T-cell response: classical and non-classical CD8 + T-cells.
Transmission of infection takes place by aerosol droplets inhaled by healthy individuals. The infection is established in the lung. Studies show that among the exposed individuals, only 30 percent have established active infection. This reduced active infection percentage is due to the pathogen encountering the first line of defense constituting the epithelial cells and the phagocytic cells like the neutrophils, monocytes, and dendritic cells. This narrative hints at the role of T-cells in the immune mechanism acting against tuberculosis, outlining their complex interplay with the other components of the immune system and the pathogen.
What Are T-Cells?
T-cells or T-lymphocytes are white blood cells developed from the thymus. From the thymus, they enter the bloodstream and are taken to the peripheral lymphoid organ This process continues until they encounter their specific antigen. Mature T-cells that have not yet encountered a specific antigen are known as naive T-cells. When a pathogen enters the body, the first line of defense gets activated. The most significant antigen-presenting cells are the dendritic cells. The dendritic cells ingest the antigen and present them to the T-cells; they are activated as a part of innate immune response; this step will activate the naive T-cells to armed effector T-cells. They are named so because of the rapid action. The effector T-cells detect the peptide antigen from different pathogens and can be classified into three classes based on these criteria, namely;
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CD8 T-cells
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CD4 T-cells
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Cytotoxic T-cells
The activation, followed by proliferation and differentiation of the naive T-cells, constitutes the primary immune response; it also produces immunological memory (memory T-cells), which protects the body from reinfection.
What Are the Immune Responses to Tuberculosis?
The immune response is crucial in controlling the infection during the initial attack. The two types of immune responses are:
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Innate immune response.
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Adaptive immune response.
1) Innate Immune Response in M. Tuberculosis Infection: It is the immunity present by birth and is the first line of defense against any foreign body. The major players here are:
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Airway epithelial cells.
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Macrophages.
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Neutrophils.
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Dendritic cells.
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Natural killer cells.
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Mast cells.
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Complement proteins.
2) Adaptive/Acquired Immune Response in M. Tuberculosis Infection: The immunity acquired by an individual due to exposure to diseases or vaccination is more complex, memorizing the pathogen and preventing reinfection.
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CD4 + T-lymphocytes.
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CD8 + T-lymphocytes.
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Humoral adaptive immunity.
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Granuloma.
What Is T-Lymphocytes' Role in Immune Response in Mycobacterium Tuberculosis?
T-lymphocytes, especially CD4 T-cells, play significant roles in the immune mechanism. CD4 T-cells deficient humans, like HIV (Human immunodeficiency virus) positive, are highly susceptible to being infected or reinfected by M. tuberculosis. Earlier CD8 T-cells were thought to be less important. However, the latest experiments and research on animals have found that the CD8 T-cells play a critical and complex role in the defense mechanism.
CD4 T-Lymphocytes:
Patients with a deficiency of CD4 T-cells have shown severe infection and susceptibility to reinfection with M. tuberculosis. These T-cells are critical because they produce the interferons required for the maturation of a specific phagosome. This process is particularly relevant in the early stages of infection.
CD8 T-Lymphocytes:
For a long time, CD8 T was considered least important, unlike the CD4 T-cells, and had no role in controlling the infection. Experiments of human models deficient in CD8 T-cells eliminated this concept. The CD8 cells help identify the antigens with class I major histocompatibility complex (MHC). The cells produce interleukins, interferons, and tumor necrosis factors that significantly control mycobacterium tuberculosis. In addition, they have cytolytic action against the bacteria through perforin and granulysin. Since it is an unknown mechanism to the pathogen, the infected cells undergo apoptosis (death of a cell). Extensive ex vivo studies (tissue taken out and returned into the body) have shown the importance of CD8 T-Cells in the host response against mycobacterium tuberculosis infection. However, the in vivo (within the living) studies showing their protective mechanism in the airway and lungs remain unclear.
Conclusion
The microorganism's ability to alter the host's immune mechanisms to eliminate the pathogen has helped it succeed over humankind for more than a thousand years. The largest vaccine trial of this decade against tuberculosis was conducted recently. The results inferred that infants boosted with vaccine targets against CD4 T-cells specifically did not confer any protection. It pushed for a need for improvised strategies to develop a vaccine suggesting that cells specific against CD8 T-cells might improve the protective responses. Evasive attributes characterize Mycobacterium tuberculosis, and immediate response at the onset of the disease should be the focus when dealing with this deadly infection.
