The creation of antibodies against SARS-Cov-2 has been in the spotlight for immune protection and vaccine development.

It is still too early to say how long immunity to SARS-Cov-2 lasts after recovery from infection, and initial reports suggesting that antibody levels decrease over time have caused alarm. However, even if antibody levels are not maintained after infection this does not mean an absence of immune memory. Recent findings are suggesting that cellular responses (like T cells) may also be important in the fight against SARS-Cov-2. But what do immune cells and antibodies actually do? And how do they help protect us against disease?

Your defences against a virus or other pathogens actually start way before antibodies get involved. The skin, mucous membranes in your mouth, nose and eyes and endothelial cells serve as physical barriers to stop a virus from getting into tissues. In fact mucous, phlegm and spit arguably deserve more appreciation as part of the immune system. If you have a cold or the flu, your body will produce more mucous to trap and clear any germs. Symptoms like coughing and sneezing occur through irritation of the mucous membranes and help expel the virus from the body. Indeed, the symptoms you may associate with being sick are actually a direct result of your immune system's response as it tries to clear the pathogen, rather than the onslaught of virus itself.

If the virus manages to get into the tissues, it will encounter inflammatory immune cells such as macrophages and neutrophils. Inflammatory immune cells are specialized cells in the detection and destruction of pathogens, ready to engulf harmful organisms (known as phagocytosis). If you have a tattoo, you can actually see your macrophages work. Macrophages will ingest the ink but cannot break it down, so to protect the surrounding tissue the macrophage will hold the ink and stay in place in your skin. During infection, inflammatory immune cells will activate antimicrobial activities such as the release of reactive oxygen species and nitric oxide to help kill the virus. Inflammatory cells also produce signals that increase permeability and stickiness of blood vessels allowing more fluid, proteins and immune cells to pass from your blood into the tissue. This accumulation of fluid and cells in the tissue at the site of infection causes swelling, redness, heat and pain, or in other words inflammation. So if you have experienced a sore arm following vaccination, rest assured that this feeling is a confirmation that your immune cells are working hard to activate an immune response. Similarly, a fever is created to support your immune system in gaining an advantage over the virus as it makes the body less favourable as a host for viral replication, which is temperature sensitive.

There is another immune cell worth mentioning at early stages of infection: the dendritic cell. Named after its long branches, or dendrites, dendritic cells move through the body sampling their environment to look for anything that is foreign and could be a threat. If the dendritic cell finds a virus, it will capture it and activate another type of immune cell - the T cell. Activation of T cells happens in lymph nodes which may swell as more immune cells come in, causing another common symptom during infection.

T cells are white blood cells that will target a given virus specifically, instead of targeting anything that is foreign like macrophages or dendritic cells. T cells come in many different flavours including cytotoxic “killer” T cells and “helper” T cells. Helper T cells are important for the activation of antibody production by B cells, which become antibody producing machines. Antibodies can protect against Covid-19 disease by binding to the virus spike protein and blocking access to cells. This is why initial vaccines against Covid-19 contain a part of the spike protein, so that the immune system can create antibodies against it even before you are infected with SARS-Cov-2. Blocking access to cells is the best way to prevent infection with the virus. However, antibodies cannot neutralize viruses that have already entered a cell, which is why killer T cells are needed.

Cytotoxic killer T cells have earned their name. Once inside a cell, the virus will hijack the cell's own machinery to replicate itself until the cell eventually dies. To alarm the immune system, the cell displays parts of the virus on its surface, which is recognized by killer T cells. These T cells can then control the infection by killing the infected cell before viral replication is complete and new viruses are released.

Initial reports suggest that cellular responses in people with severe Covid-19 disease may not be as effective as in those with a mild form of the disease. More research is needed to understand the role cellular immunity plays in the fight against SARS-Cov-2 infection and – just as important, possible reinfection. In the meantime, there may be some comfort in knowing that side-effects caused by Covid-19 vaccinations, including a sore arm or swollen lymph nodes, often reflect your immune system being activated and hopefully building immune memory against the SARS-Cov-2 virus.

Sources:
https://www.nature.com/articles/s41577-020-0402-6
https://www.nature.com/articles/s41577-020-00436-4