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Immunity: Treading turbulent waters
It has taken a pandemic for us to realise how little we know about our immune system
Vibha Varshney
Never has the word immunity been bandied about as much as during the current novel coronavirus disease (COVID-19) pandemic. Take the examples of claims of immunity boosting properties of consumer products such as hand sanitizers and even food are common.
Such claims exasperate researchers who work on the immune system. “There is not one thing called ‘immunity' and it is hard to even envisage being ‘able to improve’ it,” said Satyajit Rath, visiting professor at the Indian Institutes of Science Education and Research, Pune.
Even vaccine, that works by changing the immune response, acts only against one particular infection and cannot “improve immunity” in any general sense.
Food supplements can at best oil your engine, said Shashank Tripathi, assistant professor at the Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru. His fear is that people might get overconfident because of such claims and expose themselves to the virus, believing that they are immune, he said.
Such concerns stem from the fact that immune system is an extremely complex biological system and continues to confound scientists even over a century after scientists explained its workings; in 1908, the Nobel Prize in Physiology or Medicine was awarded to Ilya Ilyich Mechnikov and Paul Ehrlich for their contribution to explaining immune response.
What do we know about immunity?
Just like a country’s military forces, the immune system’s task is to distinguish between “self” and “non-self” and defend the body by eliminating organisms that can cause infection. For this, it depends on a variety of organs, tissues, cells and proteins spread throughout the body.
Broadly, it operates through its two arms: Innate and adaptive.
Innate immune system is the first line of defence against any incoming threat and consists of physical barriers like skin, airways and mucous layer of the digestive tract, and a cavalry of white blood cells that keeps circulating the body like a vigilant force.
But most of the pathogens that cause serious infections in humans, particularly the ever mutating, microscopic viruses, have evolved strategies to circumvent or suppress the innate immune responses.
For all such occasions, the innate immune system sends messengers to summon the adaptive immune system, which joins the war with its specialised forces — B cells and T cells.
Once alerted, the B cells tailor-make immunoglobulins (Ig), or antibodies specific for the antigen. These antibodies neutralise the pathogen by binding to its antigen and thus preventing it from attaching to host cell and entering it.
For those pathogens that have already invaded the host cells, the cytotoxic T cells — CD8+ — neutralise the pathogen by directly destroying infected cells where the pathogen is multiplying, while helper T cells — CD4+ — coordinate further attacks on the pathogen.
The war ends. But the cells do not drop their guard. Some of the B and T cells develop memory — which can persist for decades or even for a lifetime — and these cells settle inside the lymphatic organs and tissues, such as spleen and thymus.
These do not prevent reinfection but remember every pathogen they have ever overcome. The next time a familiar pathogen attacks the body, they act swiftly and in more numbers, stopping it from spreading throughout the body.
A healthy individual naturally possesses all cells of the immune system. But they proliferate and get trained only upon encountering a pathogen.
“One can measure blood levels of various immune cells to determine if immunodeficiency issues exist, but a clinician cannot tell who will have a better response to an infection based on baseline measurements before a person is sick,” said Adrian Gombart, professor, Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregan State University, US.
So what happens to a person who survives an encounter with a pathogen? Does it guarantee him the much aspired long-term immunity? Not necessarily, scientists said.
Pathogens, such as viruses that cause common cold, do not elicit a strong immune response, and thus do not leave behind much of a memory. This makes us vulnerable to reinfection.
Even vaccines against such viruses require regular booster shots to maintain immunity. Viruses are also quick to mutate and this makes immune memory against them useless.
Antibodies, which are mere proteins and thus degrade over time, do not guarantee long-term immunity.
This is the reason serosurveys, or surveys to assess the presence of antibodies in a population during the current pandemic, should be used to understand only the epidemiology of the disease and not to ascertain immunity developed by a person, to issue immunity passport or to assess herd immunity.
“We know a lot about the cells and system of our immunity but know very little about how they respond to a stimulus. Our immune system is one of the most complex biological systems on this planet.
“Millions of cells work together to counter a pathogen. Just imagine how much coordination is required. A small break in their coordination may result in disaster,” said Rakesh Singh, associate professor at biochemistry department of the Institute of Science, Banaras Hindu University, Varanasi.
Hope is mostly pinned on B and T cells that provide long-term immunity. However, though adaptive immunity has been seen in people suffering from covid-19, asymptomatic patients and contacts, researchers advice that overdependence on these might not be prudent till we have more information.
Observations suggest that a bout of the disease leads to T cell exhaustion where the surviving T cells in patients are not able to function at full capacity and leave the patients more vulnerable to secondary infection.
A study published on May 5 in journal Frontiers in Immunology reports that COVID-19 patients with severe symptoms had lower T cell counts.
The researchers suggest that instead of focusing on respiratory function, it would be better to base treatment on T cell counts and their function—patients with low T cell counts should receive care urgently.
The researchers also proposed that covid-19 virus may not be attacking T cells directly but trigger a cytokine storm, which then drives down T cell numbers.
This finding is supported by research by Shiv Pillai, professor of medicine and health sciences and technology at Harvard Medical School, US, and his team who have found that covid-19 patients with high levels of cytokines are less likely to develop long-term immunity against sarscov-2.
Pillai’s team found that the spleen and lymph nodes of deceased covid-19 patients showed a distinct lack of germinal centres, which are integral in developing long-term immune response.
These germinal centres are activated upon infection or vaccination and encourage B cells to mature into memory cells.
The paper, published in Cell on August 19, also shows that helper T cells needed by germinal centres to develop are absent in severely ill covid-19 patients.
“The immune response we saw was likely because of a virus that could not be controlled in early stages. We suspect similar things happen with any severe viral infection (like Ebola or a novel flu virus like swine flu) but these other diseases have not been studied properly before,” said Pillai.
“What we have learnt could be applied to make vaccines produce better long-lived antibodies and we are working on that,” he added.
What’s clear is that there are too many unknowns around immune response. Till we have better understanding, we can support the immune system by eating balanced healthy food and by exercising. It will provide multiple benefits.
As Tripathi explained, balanced diet and regular exercise help improve the immune response not just against COVID-19 but against all kinds of communicable and non-communicable diseases.