The Human Immune System 101: Bacterial & Viral Defenses Against the Immune System
The immune system is one of the most complex, nuanced biological systems that function to keep the human race alive each and every day. It is both specific and broad, lifelong, and short-term, inherited and acquired, all at the same time. While it defends against deadly threats such as bacteria and viruses, defects in the immune system can be just as fatal. The Immune System 101 articles describe how this contradictory system works and will summarize the variety of functions of the immune system, its importance, and its potential failings in six different articles.
3. The Human Immune System 101: Bacterial & Viral Defenses Against the Immune System
4. The Human Immune System 101: The Overactive Immune System
5. The Human Immune System 101: The Underactive Immune System
6. The Human Immune System 101: The Immune System and Cancer
The innate and adaptive immune responses can be effective at clearing a host body of threats such as bacteria and viruses. However, just as humans have evolved immune responses to defend a host against threats, those same pathogens have developed ways to dodge, evade, and trick the immune systems. Through these defense mechanisms, infections can continue to thrive despite a robust response from white blood cells, antibodies, and complement systems.
Figure 1: Microscopic view of a coronavirus particle. Shuttershock. 2021
Bacterial Defenses Against the Immune System
Different strains of bacteria employ a diverse array of strategies for evading the immune response that seeks to destroy them including physical barriers, proteolytic secretions, escaping immune cells, and a plethora of other tactics. To start, the human immune system utilizes physical and mucosal barriers to prevent bacterial infection; “the integrity of the mucosal surfaces is protected by active removal of bacteria, for example by the acid environment of the stomach, the ciliary movement in the upper respiratory tract and the continuous flushing with urine of the lower urinary tract,” (Hornef, Wick, et al., 2002, p. 1033). To combat this natural anti-microbial mechanism, bacteria utilize attachment factors known as adhesion that allow the bacteria cells to become resistant to mechanical clearance systems. An example of this mechanism in action is how the bacteria that causes whooping cough, Bordetella pertussis (B. pertussis), releases toxins that paralyze the part of the respiratory tract responsible for ciliary clearance (Hornef, Wick, et al., 2002, p. 1033). Without ciliary movement and clearance, the bacteria cells can colonize the respiratory tract and cause infections such as whooping cough.
Bacteria cells can even escape destruction by phagocytes through a number of different strategies. Yersinia pestis, the bacteria responsible for the Bubonic plague, secretes effector molecules that destabilize the cytoskeleton of phagocytes to neutralize their immune function (Finlay & McFadden, 2006, p. 771). Additionally, bacteria species have developed ways to survive after ingestion by a phagocyte; some species can physically move to escape the phagosome while others prevent the phagosome from fusing with the lysosome. Listeria monocytogenes and certain types of Rickettsia secrete a compound known as lysins, which lyse—or “break”—the vacuole containing the ingested organisms (Finlay & McFadden, 2006, p. 771). L. monocytogenes, once escaped from the lysosome, releases a toxin known as listeriolysin which interrupts the phagocyte’s cell membrane integrity in order to escape (Hornef, Wick, et al., 2002, p. 1037).
Figure 2: Listeria monocytogenes. Kateryna Kon. 2016.
Finally, certain bacteria species are able to interfere with cytokine secretion, a necessary component for the adaptive immune system activation. Mycobacteria, a genus of bacteria that includes Mycobacterium tuberculosis, produce and secrete anti-inflammatory cytokines that quiet the immune system response. Furthermore, macrophages infected with Mycobacterium “produce IL-6, which inhibits T cell activation, as well as the potent immunosuppressive cytokines IL-10,” (Hornef, Wick, et al., 2002, p. 1037). IL-10 inhibits the activation of macrophages and suppresses the production of pro-inflammatory molecules, which, overall, suppresses innate and adaptive immunity to prevent the immune system from reacting to and fighting the bacteria.
Viral Defense Against the Immune System
Viruses, although smaller and less complex than bacteria, have developed mechanisms for evading the human immune system and thriving in the face of white blood cells. The human herpes virus six (HHV-6) is particularly skilled at evading the immune system. This virus is known as an immunotropic virus, meaning it can “infect several cells implicated in the generation of both cell-mediated and humoral adaptive immune responses,” (Lusso, 2006, p. 5). By infecting cytotoxic T cells, helper T cells, and natural killer cells, HHV-6 has a direct immunosuppressive effect. Furthermore, the complement system is also a typical target for immune evasion by the herpes viruses among a large array of others. The complement system is heavily regulated by inhibitor proteins released by the host. The human cytomegalovirus can produce cellular complement inhibitors on the surface of already infected cells while HIV utilizes this same system by creating complement inhibitors on the viral envelope (Finlay & McFadden, 2006, p. 773-774).
Figure 3: Cells Infected With Cytomegalovirus, Causing Immunodeficiency in Patient. Gettyimages. 2020.
An enveloped virus can also hide from an immune cell by displaying “a wide diversity of host-derived proteins,” (Finlay & McFadden, 2006, p. 768). These proteins may include “immunoregulators, CD-family receptors, complement inhibitors, signaling ligands, or adhesion molecules, any of which can transform the extracellular virus particle into a “macro-ligand” that can stimulate immunomodulatory responses even in non-permissive host cells,” (Finlay & McFadden, 2006, p. 768-769). HIV is one of the most studied viruses with a glycoprotein envelope that uses host proteins to not only infect immune cells but hide from them as well; the virus also suppresses immune function by infecting and killing mainly CD4+ helper T cells, which are an essential component of the adaptive immune system. Without helper T cells, many other parts of the adaptive immune system such as cytotoxic T cells or B cells would not be activated. HIV essentially evades the immune system by destroying it.
Additionally, another system that viruses seem to take advantage of in the human immune system is chemokine signaling. Kaposi’s sarcoma-associated herpesvirus (KSHV) contains genes for chemokines such as vMIP-II that specifically hinders natural killer cell (NK) migration (Christiaansen, Varga, et al., 2015, p. 54). With this type of immunosuppression, the virus is able to avoid destruction by the innate immune NK cells. The measles virus (MV) and the lymphocytic choriomeningitis virus (LCMV) are able to dodge destruction by immune cells by interfering with dendritic cell (DC) proliferation (Hahm, Trifilo, et al., 2005, p. 247). One of the ways that this is achieved is through the production and release of IL-10 which “suppresses inflammatory cytokines, impairs DC maturation, and inhibits effector T cell responses,” (Christiaansen, Varga, et al., 2015, p. 54). LCMV induces host cells to produce IL-10 while viruses such as herpesvirus and pox viruses are able to encode their own IL-10 which is released as a part of viral replication.
Figure 4: 3D Representation of the Measles Virus. CDC Public Health Image Library. 2020
Bacteria and viruses, despite being small and simple when compared to humans, have evolved complex ways of hiding from, deactivating, and even killing cells that make up a strong immune response. Many of the viruses and bacteria that are able to hide from the immune system cause chronic infections and diseases while others cause short-term illnesses that are more virulent than they would be otherwise. A relevant example of this phenomenon is the coronavirus disease 2019 which caused a much more severe disease than other strains of the SARS viruses due to COVID-19’s ability to hide from the innate immune system (Kasuga, Zhu, et al., 2021, p. 724). In the midst of a global pandemic, it is essential to understand how our immune systems work and how these pathogens can mutate and evolve to exploit our immunity.
Christiaansen, A., Varga, S. M., & Spencer, J. V. (2015). Viral manipulation of the host immune response. Current Opinion in Immunology, 36, 54–60. https://doi.org/10.1016/j.coi.2015.06.012 Finlay, B. B., & McFadden, G. (2006). Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens. Cell, 124(4), 767–782. https://doi.org/10.1016/j.cell.2006.01.034 Hahm, B., Trifilo, M. J., Zuniga, E. I., & Oldstone, M. B. (2005). Viruses Evade the Immune System through Type I Interferon-Mediated STAT2-Dependent, but STAT1-Independent, Signaling. Immunity, 22(2), 247–257. https://doi.org/10.1016/j.immuni.2005.01.005 Hornef, M. W., Wick, M. J., Rhen, M., & Normark, S. (2002). Bacterial strategies for overcoming host innate and adaptive immune responses. Nature Immunology, 3(11), 1033–1040. https://doi.org/10.1038/ni1102-1033 Kasuga, Y., Zhu, B., Jang, K. J., & Yoo, J. S. (2021). Innate immune sensing of coronavirus and viral evasion strategies. Experimental & Molecular Medicine, 53(5), 723–736. https://doi.org/10.1038/s12276-021-00602-1 Lusso, P. (2006). HHV-6 and the immune system: mechanisms of immunomodulation and viral escape. Journal of Clinical Virology, 37, S4–S10. https://doi.org/10.1016/s1386-6532(06)70004-x
Figure 1: Microscopic view of a coronavirus particle. Shuttershock. (2021). [Illustration]. Image retrieved from https://news.arizona.edu/story/researchers-find-evidence-coronavirus-epidemic-20000-years-ago Figure 2: Kon, K. Listeria Monocytogenesis. Shuttershock. (2016). [3D Illustration]. Image retrieved from https://www.news-medical.net/health/What-is-Listeriosis.aspx Figure 3: Cells Infected With Cytomegalovirus, Causing Immunodeficiency in Patient. Gettyimages. (2020). [3D Illustration]. Image retrieved from https://www.rockefeller.edu/news/27419-unusual-patient-case-cmv-rare-immune-deficiency/ Figure 4: 3D Representation of the Measles Virus. CDC Public Health Image Library. (2020). [3D Illustration]. Image retrieved from https://www.cdc.gov/measles/symptoms/photos.html