Pathogens
Melanie Ziemer
Bio/340
August 31, 2015
Martin Winkler

Pathogens
In America today there are more viruses than there are people. (Bode Science Center, n.d.) One of the most prevalent viral diseases is herpes. “There are many different types of herpes, the most common are herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2).” (Bode Science Center, n.d.) Both types of herpes are cause by two very closely related viruses, and are spread from direct or indirect contact with contaminated persons or objects. (Bode Science Center, n.d.) Herpes simplex type 1 may appear as tiny blisters by the lips, nose, or in the eyes and herpes simplex type 2 may appear as tiny blisters on the genital area. (Bode Science Center, n.d.) This paper will be concentrating on herpes simplex type 1, the point of entry, how it interacts with normal flora of the body, how it affects the innate immune system, and how it affects the adaptive immune system.
To understand how herpes simplex 1 infects a person, it is important to understand the structure of the virus itself. The herpes simplex virus have a unique structure, they are enveloped, have double strained DNA genome that is contained a large core, and have a spherical shape. (Bode Science Center, n.d.) “The herpes simplex virus type 1 has glycoproteins on its envelope and this makes it a target for external influences.” (Kennedy, n.d.) The herpesvirus needs a host, has a slow replication process and can also have long period of latency. (Kennedy, n.d.) Herpes simplex 1 can be transmitted though kissing, sharing eating utensils, or sores on the skin. The point of entry can be direct or indirect contact with infected skin, mucous membranes, or body fluids. (Kennedy, n.d.) A potential barrier that HSV-1 might encounter is the bodies’ normal flora and the immune system.
“Skin and many other barrier epithelial surfaces are usually densely populated by normal flora.” (Davis, 1996) “Some bacterial and fungal pathogens also colonize these surfaces and attempt to outcompete the normal flora, but most of them (as well as all viruses) avoid such competition by crossing these barriers to gain access to unoccupied niches within the host.” (Davis, 1996) Normal flora helps to protects people from viruses by competing with invaders for space and nutrients, producing compounds to try and kill viruses, and lowering pH so that other bacteria cannot grow. (Davis, 1996) When the herpes simplex virus type1 tries to enter through skin contact it has a difficult time hitching a ride to get around the body’s natural defense of normal flora. Many of the time viruses as the herpes simplex type 1 will die off trying to get around the normal flora. Since herpes simplex type 1 needs a host survive, this causes a major challenge for the herpes virus to infect a person.
The innate immune system works to help defend people from viruses that can make them sick. The innate immune system works by collecting molecules, cells and tissue that protect the body against pathogens in the environment. (Paludon, Bowie, Horan, & Fitzgerald, 2011) The innate immune system consist of plasma and cells to fight off infections. “The major components of the innate immune system are epithelial barriers, phagocytic leukocytes, plasma proteins, dendritic cells, and a special type of lymphocyte called a natural killer (NK) cells.” (Paludon, Bowie, Horan, & Fitzgerald, 2011) Epithelial barriers use the epithelia of the skin by provide tight bond between cells to provide a physical barrier. The epithelial barrier also inhibits microbe growth by chemicals that are secreted by the epithelia. (Paludon, Bowie, Horan, & Fitzgerald, 2011) If a virus passes through the epithelial barrier phagocytes will ingest the microbes and can chemically destroy them. Dendritic cells are important in the initial defense against a virus because they make various cytokines to respond to various microbes. Plasma proteins bind microbes to help eliminate them. Natural killer cells (NK) have receptor to find cells that are damaged or distressed and then will kill these cells, to prevent further infection. (Paludon, Bowie, Horan, & Fitzgerald, 2011) These 5 functions work together to prevent the herpesvirus from spreading and infecting a person. “The innate immune is the first line of defense and play a crucial role in controlling the infection.” (Paludon, Bowie, Horan, & Fitzgerald, 2011)
The challenge that the herpes simplex type 1 may encounter is the workings of the innate immune system. Invasion of the innate immune system is very important for the herpesvirus because they are large, have a slow replication cycle, and their ability of latency. (Whitley, 1996) Replication of the virus starts within minutes of the hijacking of the host cell. “To successfully colonize the host the herpesvirus needs to invad and modulate host responses at all times.” (Whitley, 1996) “To do this the herpesvirus must evade the innate immune system by avoiding the sensing of pattern recognition receptors (PRR), blocking the action of PPRs, and prohibit signaling pathways and gene expression.” (Whitley, 1996) Herpes simplex type 1 also counteracts the delivery of pathogen-associated molecular patterns (PAMP) from the cytoplasm to the endosomal compartment. (Whitley, 1996) This allows the herpesvirus to replicate without being noticed by the NK cells.
When the innate immunity cannot stop a virus the adaptive immune system comes into play. “The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogen growth.” (Chew, Taylor, & Mossman, 2009) “There are two adaptive immune responses, they are humoral immunity, mediated by antibodies produced by B lymphocytes, and cell-mediated immunity, mediated by T lymphocytes. B lymphocytes are the only cells that produce antibodies.” (Chew, Taylor, & Mossman, 2009) B cells recognize antigens and secrete large amount of antibodies to bind to the microbe and neutralize it. T lymphocytes recognize peptide fragments that display special molecules called MHC. (Chew, Taylor, & Mossman, 2009) This ensures that T cells are able to recognize antigens that are floating in cytosol or that are in ingested vesicles. There are two subset of T cells CD4+, secretes soluble molecules that help B cells and CD8+, secretes soluble mediators that directly kill the virus. (Chew, Taylor, & Mossman, 2009)
The adaptive immune system work to neutralize the herpesvirus. Neutralizing the antibodies in the herpes virus will take T cells to infiltrate the cell in early infection and will have to contribute heavily to the immune control and the cytolysis. (Bode Science Center, n.d.) The T cell that would be the most effective is CD8+, this would go directly to the herpesvirus and kill the infection. This will help prevent the establishment of latency in the herpes simplex virus type 1. This will stop another herpes outbreak in the future.
Herpes simplex type 1 is a very challenging virus. There is no cure for the herpes virus, there are only ways to limit the amount of outbreaks. Therefor it is very important to know the point of entry can be through direct or indirect contact. That a person’s normal flora works hard at preventing the herpesvirus from finding a host cell and replicate and the innate and adaptive immune system are still looking for ways to overcome this virus. This is the path that the herpes simplex virus type 1 has to follow to navigate the human immune system and establish infection.

References
Bode Science Center. (n.d.). Herpes Simplex Virus HSV. Retrieved from http://www.bode-science-center.com/center/relevant-pathogens-from-a-z/herpes-simplex.html
Chew, T., Taylor, K.E., & Mossman, K.L. (2009, Dec). Innate and Adaptive Immune Responses to Herpes Simplex Virus. Viruses, 1(3), 979-1002. doi:10.3390/v1030979
Davis, C. (1996). Medical Microbiology (4th ed.). Galveston, TX: University of Texas Medical Branch of Galveston.
Kennedy, R. (n.d.). Herpes Simplex Virus. Retrieved from http://www.medical-library.net/herpes_simplex_virus.html
Paludon, S. R., Bowie, A. G., Horan, K. A., & Fitzgerald, K. A. (2011, Feb). Recognition of Herpesvirus by innate immune system. Nat Rev Immunol, 11(2), 143-154. doi:10.1038/nri2937
Whitley, R. (1996). Herpesvirus. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK8157