Dr. Dionna Williams
July 5, 2018
The Immune System and Viruses
The immune system, like any other body system, is a complex system with multi-layers of different cells and proteins that factor into its functionality and processes. This particular topic caught my interest due to its complexity and captivity that I have not felt as strongly in other topics. Specifically, I chose to study how certain viruses (the Ebola virus) affects the immune system of vertebrates , and which specific cells in the system respond to this attack. After reading a book about viruses, I became intrigued by its ability to deteriorate a body so rapidly. I think this would serve as a great opportunity for me to learn more in depth about what I might pursue in the future. I researched the topic and wrote a summary of what I learnt about the immune system and how Ebola affects it, then searched for recent discoveries of the immune system itself, due to difficulties finding recent discoveries of the virus.
To begin with, the immune system is simply a network of cells, tissues and organs that serve a similar function: protection of the body from infectious diseases and viruses. As stated previously, there are several layers of protection. First, there are physical barriers that prevent the pathogens from entering. These include the microbiota, the skin, mucous, and stomach acid (HCl).
The second line of defense is comprised of nonspecific phagocytes (leukocytes), such as neutrophils, eosinophils and dendritic cells. These two lines of defense are categorized as innate immunity. Though phagocytes are generally nonspecific, they can be directed to specific locations by cytokines. As the phagocyte captures or engulfs a pathogen, it leads it into a phagosome, which fuses with lysosome to form a phagolysosome. The pathogen is then digested and killed. Neutrophils are the first cells to arrive in an infection, and move to the site of infection by chemotaxis, which is the movement of a cell or part to a low concentration gradient. Dendritic cells are links between the innate and adaptive immune systems because they present antigens to T cells.
Adaptive immunity (the third line of defense) is the third line of defense, and is highly specific. It is slower in response time. It comprises of lymphocytes— B cells and T cells. The major histocompatibility complex (MHC) is a type of cell surface protein that is used in the adaptive immune system to identify foreign entities. The molecule binds to antigens and displays them on its cell surface for identification by T-cells. The antigen marker can either be self or non-self, preventing the immune system from attacking its cells. MHCs are categorized into three groups, I, II, and III. Class I molecules can only be recognized by CD8 molecules while class II can be recognized by CD4 receptors.
B lymphocytes (plasma cells) are responsible for producing antibodies. They are responsible for the immunity in the immune system. Most B cells remain inactive until they encounter a foreign entity. T cells attack infected cells and protect the organism against pathogens. T cells become T helper cells or T suppressor cells. The TH cell triggers other T and B cells by releasing cytokines. Cytotoxic T releases perforin that forms a pore for the delivery of granzymes. These granzymes program for apoptosis.
The Ebola virus is a highly infectious virus that works by inhibiting interferon, which is a protein released in response to the entry of a virus, that has the property of inhibiting virus replication. This is also found in many other viruses. Ebola was first identified by Dr. Piot and his colleagues through a blood vial that flew from Zaire in the DRC. The virus was in a sample of blood taken from a sick nun (possibly Mayinga’s).“When we opened the thermos, we saw that one of the vials was broken and blood was mixing with the water from the melted ice," says Piot. Although they first suspected it to be yellow fever, they soon found out that it looked similar to Marburg, which is another Filovirus. He and his colleagues traveled to Zaire to help the outbreak, and have made crucial discoveries about the virus and its method of spreading. Dr. Piot describes his discovery as incredibly exciting, and even states that he was not scared at all to deal with this foreign BSL-4 pathogen. They decided to name the virus after a river in Zaire.
Researchers have found that one of Ebola’s proteins called VP24 binds to and inhibits a transport protein on the surface of immune cells that engage in the interferon pathway. Once the virus penetrates the physical barriers, it targets dendritic cells. The faulty dendritic cells fail to signal the T cells, and so the antibodies do not activate. The virus then replicates rapidly.
Ebola infects predominantly the liver, where it kills cells that produce clotting proteins and other factors in the blood plasma. The virus also damages the cells that make steroids in the adrenal gland, and therefore the body is not able to regulate blood pressure. This often leads to circulatory failure. According to some sources, Ebola also produces inflammatory signaling proteins and nitric oxide which damage the lining of blood vessels. This damage of the linings is one of the main symptoms of an Ebola infection. The Ebola virus is still being researched to this day, and many researchers are progressing to find a new cure.
Though an official recent discovery or breakthrough for the EBOV has not yet been published, a recent discovery in Australia may help medicine progress in aspects of the immune system. A gene called C6orf106 regulates the production of certain cytokines to keep our immune response in check. Though this gene was discovered centuries ago, its true potential—possibly treating cancer, diabetes, and rheumatoid arthritis—has just recently been discovered. CSIRO is continuing their research in hopes of a new discovery (They haven’t given the gene an official name yet, and are currently asking for name suggestions!).
The course has helped me have a better understanding of what it is like in the clinical field in aspects of patient interviews, med school prep, and the hospital tour. It has also helped augment my medical and general biology knowledge that I have not known before, with additional medical skills. The labs, including the dissection and the blood typing, the suturing, the IV set up and the auscultation skills are all skills that are I have truly connected with and acquired. The lessons themselves were specific and detailed yet interesting and fun to follow.
This medical intensive course has truly exceeded my expectations, and I am convinced that medicine is the path that I wish to pursue in the future. Though I can list several different favorable memories from this two week program, I think the most remarkable memory I have was touring the hospital and the labs inside. I imagined what it would be like for me to work in that medical environment, and it sparked a greater interest in the field. It was also during this course when I realized that I wanted to pursue both research and medicine at the same time, which is my most significant takeaway from this program.