Explained: Antibodies and Immunity - How It Works

Why does the same virus cause mild infections in some but severe disease in others? A doctor decodes.

4 min read
COVID-19: What are antibodies and what is immunity? A doctor explains.

The immune system is usually in a fine balance - an immune response that is too strong, too weak, or one that occurs at the wrong time - can all cause problems. While people with weak immune systems are at a higher risk of severe infections, for most of us, it might be more important to think of an immune system that is out of balance as the cause of severe infections.

HIV/AIDS is a striking example of an imbalance in the immune system. HIV can cause acquired immunodeficiency and predispose one to severe infections, but it can also result in the immune system attacking the body’s own tissues.

How is the immune system strong enough to attack the body’s own tissues but so weak that it can’t fight other infections? HIV destroys a certain type of WBC know as helper T cells, which help direct the immune system.

There are two subsets of helper T cells - type 1 helper T cells (Th1 helper T cells) and type 2 helper T cells (Th2 helper T cells).

When these cells are in balance, the immune system functions well. However, when there is an imbalance between the Th1 and Th2 cells, the immune system may either be predisposed to severe infections or the immune system may attack its own tissues.

Diabetes, heart disease, and ageing can affect the balance between these cells and can impede the immune response to infections. It is possible that the disturbance in the balance of the immune system has contributed to the rise of the dark side of COVID-19; it preys on the weakest amongst us.

What Are Antibodies?

A set of WBCs called B cells are responsible for another fine immune balance, one that relates to antibodies. When a virus infects a human host, human WBCs detect certain viral antigens and produce antibodies against the virus. These antibodies bind to the viral antigens and form an antigen-antibody complex, and the complex along with the neutralised virus is gobbled up by WBCs and destroyed.

Some antibodies remain in the body for a long time, ready to rapidly bind and neutralise the same virus if encountered. These antibodies can also partially protect against similar viruses and this partial protection is called cross immunity.

While cross immunity can be protective, it can also be detrimental, and a fine balance separates the two. If infection by a common cold causing coronavirus provides partial cross immunity against SARS-CoV-2, then those with antibodies against common cold coronaviruses might have some protection against COVID-19.

Children have peculiar behavioural patterns and an inherent inability to maintain social distance. This results in frequent coronavirus infections that in a sense ‘vaccinates’ them and gives them a higher concentration of antibodies.

If it turns out that common cold causing coronaviruses provide partial cross immunity against SARS-CoV-2, this might explain why children with their frequent colds and high antibodies are less likely to have severe COVID-19.

With ageing, the elderly also lose the ability to maintain high levels of antibodies. This may explain why the elderly have less cross immunity against COVID-19 and therefore have a more severe infection.

What Decides Whether the Infection I'll Get Will be Severe or Mild?

One question, common to many viral diseases, has long been unanswered. Why does the same virus cause mild infections in some but severe disease in others?

Recently, scientists have found that certain genetic and immunological differences between humans result in different immune responses to the same virus causing a severe cytokine storm in response to a viral infection in some, that may be mild in some others. This is not because of a weak immune system; rather, it is because of an excessively strong immune response that goes out of control. These subtle genetic and immunological differences have served as an entry point to developing new preventive and therapeutic strategies against viral infection.

When the immune system detects viral antigens, it produces antibodies to defeat the virus. The immune system also remembers the influenza virus and a memory of its antigen is stored in special memory WBCs. The next time the immune system detects the same virus, the memory cells will rapidly produce antibodies, and the virus will get neutralised faster than the first time around.

The term original antigenic sin (OAS) was first used to describe how the first influenza infection in a person shapes outcomes during future influenza infections.

Although ‘sin’ is usually connoted as a negative attribute, OAS-like responses are neither inherently ‘good’ nor ‘bad.’ It all depends on the context, and the 2009 H1N1 pandemic provided excellent context.

During that pandemic, older individuals infected by the 1918 H1N1 strain had lower mortality rates. But those born during the 1957 H2N2 Asian flu pandemic had a much higher mortality. This led to the theory that while OAS can be beneficial in enhancing protection against some viruses, the same phenomenon can also worsen future infections.

The doctrine of the OAS explains that past exposures to viruses can provide protection against future infections or make them worse. For some, past infections can prime their immune system to fight future infections, for others, past infections may prime them for worsening. There’s a fine immune balance that separates good and bad outcomes, and we are still just beginning to understand the involved mechanisms.

The immune system is a frontier of scientific discovery in medicine, and immunologists will likely provide us crucial insights in the battle against future pandemics.

(Dr Rajesh Parikh is the Director of Medical Research and Hon. Neuropsychiatrist at Jaslok Hospital and Research Centre, Mumbai. He is also a co-author of the book “The Coronavirus: What you Need to Know about the Global Pandemic”.)

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