Tuesday, November 5, 2013
Role of Mucosal Immunity in HSV Infection
Herpes Simplex Virus (HSV) is one a virus that plagues many people as it is one of the most common viruses. It is transmitted by physical contact such as drinking, sexual contact, kissing, etc. There has yet to be a vaccine or cure to HSV which is interesting as it has been around so long and no cure has yet to be found. We have many defenses such as mucosal immunity but somehow this seems to make it through. We learned about many systems that play a role in mucosal immunity but for HSV the most pertinent would be vaginal muscosa. Mucosa has IgA secretory antibodies that can help defend from pathogens as well as other several cytokines.
In the paper, Role of Mucosal Immunity in HSV Infection, by Kuklin et. al. they were examining the purpose of mucosal immunity in HSV infection. Mice were immunized through the nose with 3 different variables: glycoprotein B, glycoprotein D, or VV. The mice were challenged with different concentrations of plaque forming units (pfu), a unit of particles capable of forming plaques. The mice were examined on a scale of 1-5 based on their severity. In order to measure monoclonal antibodies, they used anti-CD8+ and anti-CD4+ mAbs. This was analyszed with flow cytometry analysis (the use of an electronic detection to detect small particles in fluid such as mAb). This experiment lasted for 30 days.
After the initial immunization experiment they wanted to measure T cell depletion in vivo so they injected them with 2mg/mouse DP (DepoProvera). DP is a progesterone shot and it aims to regulate the period cycle of the female mice; similar to the DP shots women take as birth control. They challenged the mice with 5 X 10 ⁶ pfu of HSV. Anti CD8+ and anti CD4+ mAbs were given to the mice on day 2 and day 4. The mice were sacrificed after 10 days of this second experiment and there cells were combined and analyzed using two-color flow cytometry. Using samples of serum and vaginal secretion, they were able to use the same process as before to measure Ab production.
As a result from the experimentation, the immunization with the vectors led to high Ab vaginal production. The vaginal immunity was not enough to end viral invasion but after vaccination, the animals were able to suppress some of the disease expression such as the clinical signs of red bumps, etc. This lead to a new question: "What protects mucosally immunized mice from clinical disease?" This is where the CD4+ and CD8+ mAb came into play and as a result CD4+ depleted animals had higher concentrations of plaques than CD8+ thus they concluded that CD4+ is more important for mucosal immunity than CD8+ T cells in this capacity. The same conclusion was determined when they knocked out CD4+ mice and Beta2m and CD4+ knockout mice were more susceptible than Beta2m.
This experimentation opens up the light to the multiple immune responses that take place against a pathogen. Although our vaginal mucosal immunity did not prove to be sufficient enough to suppress the HSV infection, CD4+ cell were able to step in and take on the challenge. The CD4+ T cells are the principal effector against HSV infection. Anti-HSV vaccines do not provide barriers but they do help with clinical expression of the disease.
This is relevant to our class because we have many defense systems although the primary defenses fail us sometimes or are not as effective such as the mucosal barrier. We have secondary defenses such as macrophages, neutrophils, and CTL's. We have layers of defense and this is why our bodies can fight off a disease although it won't be cured; we can suppress disease and help prevent the expression as we saw with the CD4+ T cells in this example.