Understanding Immune Response to COVID-19

Although the immune response to COVID-19 remains to be understood entirely, science has come a long way in breaking down the basics of immunology in COVID-19. While the immune system may be one of the most complicated systems to understand, we will try to explore how our immune system reacts to the coronavirus infection with the help of an example.

Let us assume that your house is your body, and the virus is someone who’s trying to break into your house.

For the man to break into your house, he has to find portals of entry- doors, windows etc. The windows are closed from inside. And the front door is locked. However, the man has a tool to pick your lock.

In this case, the door for the virus is your respiratory tract. The virus enters through your nose, and binds to ACE 2 receptors on your cells (lock) via its spike protein (key) and gains entry into your body (house).

You hear the sound of the creaking door and the man’s footsteps. It’s dark and you do not know who it is, but in an alarm, you grab your phone and a stick and spring into action. You creep towards your bedroom door, being as quiet as possible. You also grab a flashlight.

This is what it’s like to have your innate immune response activated. Cells involved in this process, primarily macrophages, NK cells, dendritic cells, detect foreign invasion of tissue, much like you perceived the man’s footsteps.

However, like you, these cells are in the dark and do not recognize the new virus. The response is nonspecific. You don’t know your intruder and you’re not sure if you’ll be able to beat him with a stick. Thus, the intruder has a good chance of “evading your attack”. You are in a vulnerable position. Similarly, SARS COV-2 also evades our rapid, innate immunity. This allows the virus to proliferate, uninhibited in the tissue and continue its journey further. (You can think of this as the intruder calling in on his friends to join him because he no longer sees your attacks as a threat.)

You know you alone are not capable of handling the situation. Therefore, you call the cops and try your best to describe the events you have witnessed, and specifically, the man you have seen from your bedroom door.

Cells involved in the innate system do something similar. They sense something is wrong and send danger signals, also called “cytokines”. These cytokines “recruit” lymphocytes (cops) to assist their fight in the situation.

Here’s where things start to look slightly different. There are essentially two types of lymphocytes- T cells and B cells. T cells are primarily responsible for cell-mediated immunity, while B cells are responsible for humoral (antibody-mediated) immunity.

Let’s try to understand what happens at a microscopic level. Cells involved in the innate immune response also act as Antigen Presenting Cells- meaning; they ingest proteins released by the virus and break them down into simpler substances called peptides. These cells then present these peptides to T cells. These T cells are naive T cells-they need to be presented with an antigen in order to become activated. It’s kind of safe to say that cells involved in the innate immune system hand over the details of the intruder to the cops. The cops then decide which department should take over the case.

Let us assume the cop you were talking to on the phone was a fresh recruit. Being inexperienced and thus, “naïve”, he knows he would not completely comprehend the know-how of the situation. So, he decides to take help from some senior officials in his department. He passes on the message to them and also tries to observe and react the same way they would in this situation.

Similarly, naive T cells send cytokines (interleukins) to recruit another type of T cell, called the CD4+ Helper T cell. The Helper T cell coordinates both types of immunity in your body. At the same time, the naive T cell itself differentiates into an effector cell.

Let us assume for the sake of understanding that the head of the department (CD4+ T cell) decides to send two groups of cops-one armed with a rifle and the other armed with handcuffs in order to restrain the intruders. The two groups reach your house and handle the situation as instructed.

Similarly, Helper T cells stimulate B cells which secrete antibodies. These antibodies essentially bind to antigens and coat them (you can imagine this as the criminals being restrained by the group carrying handcuffs). The antigen, thus coated, is easily digested off by phagocytes like macrophages. This is your antibody-mediated or humoral immune response.

The other group of cops aims to fire at the intruders. This group would comprise the CD8+ Cytotoxic T cells, which directly kill the infected cell by creating pores in its membrane (kind of similar to the intruders being shot). This comprises the cell-mediated immune response.

Usually, there are laws binding the cops from going into a full-blown violent attack in such situations. Similarly, there are T regulatory cells that keep your immune response in check. The fight must stop at some point. In SARS COV-2 infection, this regulation is lost in some people. This creates a hyper-inflammatory state called “the cytokine storm”, where a large number of cytokines are being released and so there is an enhanced recruitment of immune cells. The fight no longer remains about the virus, which may have long since been dealt with. Instead, the system starts attacking your own body. This is why there are so many varied manifestations in SARS COV-2 patients.

Both the cell mediated and antibody mediated immunity components of adaptive immunity, which is a slow response, take longer to develop but are long-lasting. This is the immunity, which will keep you protected the next time the same organism infects you.

Now that the situation has been dealt with, the intruders caught and taken away, all that remains with you is the memory of the incident. Some of your memory is also shared by the cops. One of the cops advises you to install an alarm system specific to intruders of this kind.

Although slightly unrealistic to our situation, for the sake of understanding how immunity develops in our body, you install an alarm system that goes off only when the same intruder breaks into your house again. This time you would not have to wait to call the cops-they would be directly alerted, know precisely what to do and the situation and the intruder would be dealt with quicker and more effectively. This is carried out by the memory B cells in the body. These memory B cells are promptly reactivated upon infection with the antigen or virus. They can effectively protect the body from the severe effects of the disease upon infection with the same virus the next time.

This is similar to how some of these B cells and T cells work. They are called “Memory B cells” and “Memory T cells”. They remain quietly moving along the lymphatic system in your body or rest in lymphoid organs, somewhat like veterans of the war, but immediately come into action as soon as the same virus strikes again. This time they develop a rapid and more effective immune response and clear off the virus quickly.

Overall, research has shown that it takes about 1-2 weeks after symptom onset for SARS COV-2 patients to develop cell-mediated immunity. Although how long it can last is still somewhat unclear. It is, however expected to last for at least a few years.

It takes around the same time for antibodies to develop. The first to appear are IgM and IgA antibodies by day 5 to 7 and IgG antibodies by day 7 to 10 from the onset of symptoms. In general, serum IgA and IgM titers decline after four weeks and IgG antibodies may last for 3 6 months. However, antibodies are not detected in all SARS Cov 2 patients. Research shows that people who have recovered from COVID-19 may have different titers of antibodies, which may be affected by the amount of virus in the body during the infection period, among other factors.

There are still many questions regarding immune response in COVID-19, one of the major ones being the wide range of severity of COVID-19 infection. Why is it that only some people develop cytokine storms while others do not even suffer from clinical disease? Why is there so much variation in the immune response to COVID-19? How long will immunity last in patients who have recovered from COVID-19?

A lot of research is being done to answer some of these questions. But there is no doubt we’ve come a long way since March. Hopefully, with vaccines trying to achieve a similar response and a long-lasting one, we will be able to answer some of these questions in the near future.

Until then, we suggest you install an alarm system in your house, wear a mask and maintain hand hygiene.

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About author

Dr. Pankti Pandya is currently an MBBS intern in Shree Krishna Hospital, Anand, Gujarat. In free time, PanktiI like to read books, write poems and blogs and play guitar in her free time. You can read more about her blog here: https://lookingforagreaterperhaps.wordpress.com/

Article first appeared on twitter: https://twitter.com/pankti4299/status/1369217935063977986

Edited by: Anjali Mahilkar

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