Colorised scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Caption and photo: niaid/Flickr, CC BY 2.0.
A vaccine prepares a person to fight off an infection by training the immune system. So it’s useful to know how the immune system works in order to understand why vaccines are important, and why we’re all waiting for one against the novel coronavirus (SARS-CoV-2).
Various cells called sentinel cells first recognise any invading virus. These cells are the first line of defence. Sentinel cells include macrophages, mast cells and dendritic cells. Viruses possess specific molecules called pathogen-associated molecular patterns (PAMPs). Complementarily, sentinel cells possess pattern recognition receptors (PRRs) that can detect the viruses’ PAMPs.
Not all strains of the same virus have the same structure. As a result, sentinel cells can’t recognise the PAMPs of all the strains. But instead, PRRs learn to recognise PAMPs that are commonly shared by different strains.
At the same time, viruses also have some strategies to escape recognition. For example, studies suggest the novel coronavirus may be inducing the formation of double-membrane structures inside sentinel cells. These structures lack PRRs, so the virus goes unrecognised. Further research might elucidate other evasive mechanisms.
About 15% of COVID-19 patients develop pneumonia; about 5% of them go on to have multiple organ failure. During such critical conditions, the immune response is critically impaired.
In the immune system, white blood cells patrol the body – through the blood – looking for the virus. Of the different types of white blood cells, lymphocytes are particularly important because they recognise viruses and secrete antibodies against them. In people with a severe form of COVID-19, the number of lymphocytes is sharply reduced.
Lymphocytes include T-cells, B-cells and natural killer (NK) cells. T-cells develop from the thymus gland. B-cells and NK cells originate from the bone marrow. T-cells are of two types: helper T-cells and cytotoxic T-cells. Helper T-cells activate various other immune cells and release signalling molecules called cytokines. Cytotoxic T-cells go for the virus, release toxic granules into them and kill them.
B-cells perform a diverse range of functions, notably secreting antibodies. NK cells kill those cells that have already been infected by the virus. This prevents the virus from spreading further. A decrease in the number of T, B, and natural killer cells leads to a marked deterioration in the immune response of the affected individual.
A common feature among COVID-19 patients is a dropping T-cell population. Those T-cells that still remain have compromised function. B- and NK cells’ populations also decline in people with severe COVID-19.
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When any infection takes hold, the body responds by secreting antibodies that circulate in the blood for some time. They bind to the viruses, neutralise them and expel them from the body. This binding is akin to a key ‘binding’ to a lock. Specifically, the antibody recognises a particular part of the virus, called the epitope, and forms a bond with it using a part called the paratope.
Any microorganism is capable of evolving into new strains, or genetic variants, in the natural course of evolution – viruses more so.
Say antibodies are secreted against one strain. Their paratopes could develop a structural change that allows them to bind to the epitopes corresponding to this strain. However, the binding itself doesn’t destroy the viruses.
In some cases, as with the dengue virus, the virus-antibody complex keeps circulating in the bloodstream and gets attached to nearby cells. As a result, the antibody itself ends up enhancing the virus’s uptake into the cells, and allows the viral population in the body to grow faster. This process is called antibody-dependent enhancement (ADE).
We don’t yet know if ADE happens with any strains of the novel coronavirus, which predominantly replicates in cells found in the lungs. If a viral strain does become able to take advantage of ADE, our efforts to develop a vaccine could become more complicated. The Indian Council of Medical Research has planned studies to understand how the virus has changed in different parts of India since the first cases were reported in Kerala in late January.
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A phenomenon called cytokine storm leads to mortality in terminally ill COVID-19 patients. Cytokines are small proteins synthesised by several types of cells. However, they are predominantly produced by the helper T-cells and macrophages. Cytokines warn the cells of an invading virus, and stimulate them to move towards the sites of infection and inflammation to fight the virus. If white blood cells are police, the cytokines could well be their bullets.
Cytokines accelerate inflammation in the body to prevent the virus from circulating further. Controlled inflammation is essential to expel the virus – but sometimes unrestrained cytokine synthesis leads to a rampaging inflammatory response called a cytokine storm. In a COVID-19 patient, a cytokine storm elevates the patient’s status to a critical condition known as acute respiratory distress syndrome, which is often fatal.
Understanding the body’s response to the SARS-CoV-2 virus is important to comprehend the underlying mechanisms of vaccines and antiviral drugs. Coronaviruses have not popped up all of a sudden. We have been living with various human and animal coronaviruses for decades. Nevertheless, this novel coronavirus is wreaking havoc owing to its rapid rate of transmission. Further investigation will unravel the complete behavioural patterns of this virus, allowing researchers to develop a potential vaccine soon.
Niranjana Rajalakshmi is a veterinary microbiologist.