In this episode, Mumps Virus invades the parotid gland in the head, fulfilling Memory Cell’s visions of a future invasion by the virus. As Mumps Virus replicates quickly to overwhelm the white blood cells, Memory Cell tries to see the future as Plasma Cell struggles to bring him back to reality. As Memory Cell and Plasma Cell rummage through the records to find clues on the Mumps Virus, Memory Cell is still overwhelmed by the visions, prompting Plasma Cell to hit him on the head. Memory Cell then remembers that what he was seeing was actually in the past, where the white blood cells easily defeated weakened Mumps Virus from a mumps vaccine and Memory Cell made a record of the virus. Remembering what happened in the past, Plasma Cell and Memory Cell bring up a huge antibody gun to easily defeat the Mumps Virus and eliminate the infection, to the relief of the other cells.
In this blog post, I will go through what mumps is and how it arises. I will then explain how vaccines work in preventing mumps infection from becoming severe.
The mumps virus
| Schematic | Microscopic | Anime |
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Mumps is a viral infection caused by the mumps virus, an enveloped RNA virus belonging to the Paramyxoviridae family. The plasma membrane is studded with two different surface proteins: F (fusion) and HN (haemagglutinin-neuraminidase) proteins, which are designed to attach the mumps virus to host cells. Underneath the plasma membrane is a layer of matrix (M) proteins which keeps the virus together. Inside the virus is a long piece of single-stranded RNA that is covered in N (nuclear) protein. Other proteins in the virus include RNA-dependent RNA polymerase, an enzyme that copies viral RNA during viral replication, and SH (small hydrophobic) and V proteins which suppress immune responses against the mumps virus.
The mumps virus spreads among humans via the respiratory route, either by breathing in the virus or by touching respiratory droplets containing the virus. Unlike respiratory viruses such as influenza; however, the mumps virus does not typically cause respiratory symptoms. Instead, the mumps virus spreads around the body to infect different organs, producing systemic symptoms such as headaches, fever, body aches, reduced appetite and fatigue. The most notable of these organs is the parotid glands, salivary glands located in front of the ears. Mumps infection of the parotid glands causes them to swell (known as parotitis) as blood leaks into the parotid glands and white blood cells infiltrate the glands. The swelling of the parotid glands produces the painful, swollen cheeks, mirroring the virus’ appearance in the anime. The mumps virus also infects cells in the testicles (orchitis) in 10-20% men. This promotes inflammation which can lead to groin pain in infected men and reduced fertility as testosterone and sperm production are decreased. In rare cases, the virus can infect the linings of the brain and spinal cord to produce meningitis and the brain to cause encephalitis.
Mumps is rarely fatal, with treatment consisting of anti-inflammatory medication and cold packs to relieve symptoms. However, given the absence of drugs to eliminate the mumps virus and the potential long-term complications of mumps, it is imperative that mumps infection is prevented.
The adaptive immune system
The adaptive immune system consists of T cells which either bolster immune responses (helper T cells) or kill infected cells (killer T cells) and B cells which become plasma cells to produce antibodies. The adaptive immune system has two characteristics that distinguish it from the innate immune system:
- The adaptive immune system mounts specific responses to particular pathogens. Cells in the innate immune system such as neutrophils, macrophages and dendritic cells mount the same immune response to different pathogens. In contrast, not all B and T cells respond to different pathogens. Instead, specific B and T cell clones are selected to respond to a particular pathogen, where they become activated, proliferate and secrete proteins and antibodies against the pathogen.
- The adaptive immune system possesses immune memory, where the body ‘remembers’ past infections by producing memory B and T cells. This is represented in the episode by Memory Cell having flashbacks to the mumps vaccine. When the body is re-exposed to the same pathogen, memory B and T cells can quickly differentiate into plasma and effector T cells respectively. This allows the body to mount a quicker, stronger immune response against the pathogen to remove it more quickly, reducing the severity of infection so that the person shows mild or no symptoms.
How do vaccines work?
There are two ways in which immune memory can be generated. Firstly, the person can become infected by the pathogen itself (primary infection), producing symptoms of infection. This triggers an immune response to eliminate the pathogen and produce memory B and T cells. Although immune memory is generated, primary infection runs the risk of killing the person if the immune system cannot contain the proliferation or replication of the pathogen.
The second way in which immune memory can be generated is via a vaccine. Vaccines are substances that aim to produce immune memory to a particular pathogen in the body. It does this by exposing the body to attenuated/weakened or killed/inactivated forms of the pathogen or parts of the pathogen, allowing the body to produce memory B and T cells without the symptoms associated with infection. This is why the white blood cells were able to easily defeat the weakened mumps virus from the mumps vaccine, allowing Memory Cell to record the mumps virus. By developing immune memory from the vaccine, the person becomes immune to the pathogen so that it can mount a strong, rapid immune response to quickly eliminate the pathogen when it re-emerges. This is represented by the big antibody gun Plasma Cell deploys later in the episode.
Did you know? Vaccination and immunisation are two different words. Vaccination is the process of receiving a vaccine. In contrast, immunisation is the process of receiving a vaccine AND generating an immune response against the vaccine.
In the case of the mumps vaccine, the mumps virus is attenuated, meaning that the virus is able to replicate inside the body but cannot cause infection. Attenuated vaccines are beneficial in that they involve both B and T cells to generate strong immune memory against the mumps virus. Different strains of the mumps virus have been used in the mumps vaccine. The most common mumps strain used in vaccines is the Jeryl-Lynn strain which was isolated from Jeryl-Lynn Hilleman in the USA and attenuated by Merck in the 60s.
The mumps vaccine was initially given alone. However, from the 70s onwards, the mumps vaccine is part of the trivalent MMR (measles, mumps and rubella) vaccine which also contains attenuated forms of the measles and rubella viruses. Some MMR vaccines also contain the attenuated form of the varicella virus which causes chicken pox. The MMR vaccine is given twice to children who are over 12 months of age to build up immune memory against the measles, mumps, rubella and varicella viruses to prevent infection.
The progress and challenges of the mumps vaccine
The mumps vaccine has been very effective in reducing the prevalence of mumps in the community. Before the mumps vaccine was widely available, mumps was a very common childhood infection and a common cause of childhood meningitis. After the mumps vaccine was introduced, mumps cases in the US decreased by 98%. This highlights the public health value of vaccines in protecting individuals and communities against infection, preventing high numbers of infections from being reached.
However, unlike measles, rubella and chicken pox which are very effective (89-95%) in preventing infection after two doses of the MMR vaccine, the vaccine is less effective in protecting people against mumps (86%). There are also more challenges in setting up effective immune memory against mumps from the MMR vaccine. Firstly, there are safety issues associated with some mumps strains used in past MMR vaccines such as the Leningrad, Rubini and Urabe strains. These strains have a small chance of causing mumps and/or meningitis in children. This is because the viruses in attenuated vaccines may revert back to its infective form to cause disease. Due to these safety issues, these mumps strains are not used in modern MMR vaccines with most of them using the Jeryl-Lynn strain.
More concerningly, outbreaks of mumps are occurring worldwide, even among those who are vaccinated. One reason for this is that people are only vaccinated against one particular type of mumps virus (the A type). Although the vaccine protects people from being infected by type A mumps virus, they are still susceptible to non-type A mumps viruses which are circulating worldwide. Furthermore, immune memory against the mumps virus wanes over time. Hence, older people are more vulnerable to contracting and showing the symptoms of mumps compared to younger people. Nevertheless, people who received the MMR vaccine were less likely to have severe mumps infection compared to unvaccinated people. Furthermore, vaccinating adults with a third dose of the MMR vaccine has been shown to reduce the risk of contracting mumps during outbreaks. Hence, vaccines are still valuable for limiting the size of mumps outbreaks so that it does not spread to other people in different communities.
Conclusion
Mumps used to be a common childhood viral infection, producing swollen cheeks due to the swelling of the parotid glands. While mumps is rarely fatal, it can infect and damage various organs around the body, causing long-term complications. The MMR vaccine, which contains an attenuated form of the mumps virus, is a cost-effective way of protecting individuals and communities against mumps. It does this by stimulating the human body to produce memory B and T cells to set up immune memory against mumps and other viruses without causing infection. The setting up of immune memory against the mumps virus allows the human body to quickly eliminate the virus when re-exposed, preventing or reducing the severity of infection and stopping the spread of the virus. However, there are various challenges in maintaining immune memory to protect people against mumps, something that is apparent in the development of COVID-19 vaccines. If you want to learn more about the different types of vaccines, I have written a blog post about it.
In the next blog post, I will talk about how the gastrointestinal tract can protect the human body against pathogens that cause food poisoning. See you then!
References
I learnt about the mumps virus and the different diseases it causes around the body from an informative review article by Rubin et al. from the Journal of Pathology. If you want to learn more about mumps vaccines, the challenges of mumps vaccination in the modern age and how we can improve these vaccines, Almansour has you covered in Frontiers of Microbiology.