The immune defense against microorganisms is carried out with the help of two lines of defense – the first line of defense, the so-called innate immunity (innate immunity) reacts quickly but unspecifically and is mediated by certain cytokines (e.g. type I interferons) and natural killer cells (NK cells) – I had presented these mechanisms in more detail in the last post.
The second line of defense takes some time to get started after an infection, but is much more specific and also leads to the formation of an immunological memory – thus an immunity against a pathogen after a renewed infection. This part of the immune system is referred to as adaptive immunity (adaptive immunity) and is mediated, among other things, by T and B lymphocytes. (Here it should be briefly mentioned that the T lymphocytes are distinguished into so-called CD4 positive and CD8 positive T lymphocytes).
I would like to explain in more detail how adaptive immunity against viruses works in this post. However, it must be emphasized that both parts of the immune defense – innate and adaptive immunity – work closely together to eliminate viruses from our body. The separation made here is more for didactic reasons.
In the adaptive immune system, the so-called cytotoxic T lymphocytes (CTL = cytotoxic T lymphocytes) are responsible for the efficient killing of cells that are infected with viruses. However, these cytotoxic T lymphocytes have to develop first – this is also called differentiation in immunology. Naive CD8 positive T lymphocytes (which lack the ability to kill) differentiate into CTLs in response to certain stimuli during a virus infection. The large number of virus-specific CTLs that have formed recognize virus-infected cells by the fact that smallest components of the viruses reach the surface of the infected cell and thus mark the infected cells for the CTLs. Within the cytoplasm of differentiated CTLs there are numerous granules that contain proteins such as perforin and granzyme, with the help of which a target cell can be killed. In addition, differentiated CTLs can secrete cytokines, mainly interferon-γ (a type II interferon), which activates phagocytes (scavenger cells) that clear up the cell debris that has formed during the inflammatory reaction. CTLs are therefore similar in function to NK cells – but are even more specific, or if you like, even more “deadly”.
So we can already state here that for the fight against a virus infection, the normal function of the NK cells and the CD8 positive T lymphocytes, from which so-called cytotoxic T lymphocytes develop as part of the immune response, is important. Since
- neither interferon preparations (Betaferon, Rebif, Avonex, Plegidy, Extavia), nor glatiramer acetate (Copaxone, Clift),
- nor dimethyl fumarate (Tecfidera) or natalizumab (Tysabri)
reduce the function of these two cell types, it is very unlikely that the use of these drugs for the treatment of MS will affect the ability of MS patients to defend against viruses. For the other drugs that directly interfere with cellular immunity, the considerations must be somewhat more differentiated, which I will try to do in the follow-up articles.
Finally, I would like to conclude the post with an explanation of how a (long-lasting) immunity develops after successful defense against viruses. This is based on the formation of antibodies against components of the virus. These antibodies (or the cells that produce antibodies) are formed in the germinal centers of the lymph nodes through the interaction of CD4 positive T helper cells and B lymphocytes. However, antibodies can only reach viruses extracellularly – once the viruses have already invaded the cells and started to multiply in the cell, they are not accessible to antibodies. Therefore, the protective effect of the antibodies is especially given after a previous infection (or vaccination). Antiviral antibodies bind immediately to the virus envelope or capsid proteins in this case and then act as neutralizing antibodies that prevent viruses from attaching to the cell membrane and thus also entering host cells. Thus, antibodies prevent both infection and spread from cell to cell.
If, however, no immunity exists yet (as is now the case with the Corona epidemic), antibodies alone are not able to eliminate the virus on their own in an already established infection. This is also a very important reason why I am relatively calm in the current situation with regard to B-cell depleting MS therapies such as ocrelizumab (and rituximab). But I will explain this topic a little more in detail in one of the next posts.
