By Don Syiem
The immune system is very complicated and arguably the most complex structure of the human body outside the brain. It’s an intricate network of cells and molecules which are mobilized to protect us from dangerous viruses, bacteria and other pathogens. The components of the immune system recognize, summon, amplify, enrage, quieten, and transform one another according to need. In the context of the ongoing pandemic Covid-19 a few questions arise on the functioning of the immune system, such as, why some people become extremely ill while others don’t? Can infected people be sickened by the same virus again? Will vaccination work? To answer these questions, we must first understand how the immune system works. The key player in the immune system is the white blood cells (WBC), which travel throughout the body using the blood and lymphatic vessels screening for invading microbes.
The immunity response acts in phases. The three phases involve detecting a threat, summoning help, and launching the counterattack. It begins as soon as a virus drifts into the airways, and infiltrates the cells that line them. Virus latches onto the host cell via specific structures on their surface which facilitate their entry. When host cells sense molecules uncommon to humans, they produce proteins called cytokines. Cytokines play a role in initiating inflammatory response and regulating host defense against pathogens. Other cells of the host act like alarms, activating a diverse squad of WBCs that attack the intruding viruses—swallowing and digesting them, bombarding them with destructive chemicals, and releasing yet more cytokines. Yet others, directly interfere with viral reproduction by secreting molecules called interferons which also heighten the anti-viral defenses of nearby cells. These aggressive acts lead to inflammation. Redness, heat, swelling, soreness are all signs of the immune system working.
The defense and counter measures outlined above involve the i) Innate immunity (ii) Adaptive immunity and iii) Passive immunity. Innate immunity is a fast-immune response that provides the first line of immunological defense against infections. It comprises of different regiment of battle tanks (cells) with exotic names such as eosinophils, monocytes, macrophages, natural killer cells and a series of soluble mediators (chemical weapons) with equally difficult names. Like battle tanks in a war, these cells spew bullets and shells on the enemy. The cell’s battle tank (macrophages) engulfs the enemy, while the eosinophils and others spew chemicals that kills the viruses. Adaptive immunity on the other hand is a precise but slow immune response which can take several days for activation and is mediated by the T and B lymphocytes (classes of WBCs). These are ground troops soldiers capable of identifying and eliminating the enemy. Unlike the innate branch of the immune system, the adaptive one has memory which is used for future fights with the same enemy. Importantly, like in war, immune responses are inherently violent where cells are destroyed and harmful chemicals are unleashed.
The initial response is part of the innate immune system occurring within minutes of the virus’s entry. It uses components that are shared among most animals and it is wide-ranging, attacking anything that seems both nonhuman and dangerous. However, the innate immune system lacks precision although it makes up for in speed. Its job is to shut down an infection as soon as possible. Failing that, it buys time for the second phase of the immune response: bringing in the specialists. As in war, you first bomb, send in the tanks (which kills indiscriminately) and finally the troops which can identify (because they wear different uniforms) and neutralize the enemy.
Amid all the fighting in your airways, specific cells grab small fragments of virus and carry these to the lymph nodes, where highly specialized WBC (T-cells) are waiting. The T-cells are selective and preprogrammed defenders. Each is built a little differently, and comes ready-made to attack the mountain of pathogens that has multiplied. For any new virus, you probably have a T-cell somewhere that could theoretically fight it. Your body just has to find and mobilize that cell. The lymph nodes contain an assortment of T-cell soldiers enclosed in a camp, each of which has just one type of target to fight. The messenger cell carrying fragments of the enemies like a picture, showing it to the camp to help in identifying so that the wrong target is not shot down. When an enemy is found, the specific soldier arms up and multiplies itself into an entire battalion, which then marches off to confront the enemy.
Amongst the different types of T cells, some are professional killer squads which blow up the infected respiratory cells in which viruses are hiding. Others are helpers, which boost the rest of the immune system. These helper T-cells activate the B-cells that produce antibodies (immunoglobulins). These are small molecules that can neutralize viruses by gluing up those structures that viruses use to latch on to their hosts. Roughly speaking antibodies mop up the viruses that are floating around outside our cells, while T-cells kill the ones that have already worked their way inside. T-cells do demolition; antibodies do the cleanup.
Antibodies are produced by different groups of B-cells. The first group is quick and short-lived, and swiftly unleashes a massive antibody tidal wave before fading off. The second group is slower but long-lasting, and produces calmer antibody waves that sweep over the body continuously. The body makes different antibodies to fight different infections. Immunoglobulin M (IgM): Found mainly in blood and lymph fluid is the first antibody the body makes when it fights a new infection. Immunoglobulin A (IgA) is found in the respiratory tract, digestive system, saliva, tears, and breast milk. Immunoglobulin G (IgG) is the most common antibody and found in blood and other body fluids. IgMs and IgAs can be detected early during the 1st week of symptom onset, whereas IgG can be detected at around 14 days after the initiation of symptoms. It is not known how long the protecting levels of these antibodies will remain active.
One of the most intriguing and less understood question is what happens after you’re infected and whether you could be infected again. Coming back to Covid-19, researchers still don’t know how much protection the leftover antibodies and memory cells might offer against the same virus if one is re-infected as there are reports of people losing these specific antibodies over a period of time. However, experts say that although you may not have measurable antibodies doesn’t mean that you aren’t immune. Your T-cells could continue to provide adaptive immunity even if the antibodies fade out. Memory B-cells, if they persist, could quickly replenish antibody levels. Its not only antibody quantity that matters, but also the quality of the antibody is as important. Quality defines which part of the virus the antibodies bind to, or how well they stick.
Could the ghosts of your previous colds help protect you from Covid-19, even if you have never been infected by this new coronavirus: Information from other coronaviruses like SARS-CoV and MERS CoV could help understand the complex interaction between SARS-CoV-2 (the virus causing Covid-19) and the host’s immune system. This is still an evolving area of study. The complexity of the Covid-19 pathogenesis is highlighted in a recent report published in the journal Nature by scientists from the National University of Singapore (NUS). Their findings suggest that infection and exposure to any coronaviruses induce long-lasting memory T cells, which could help in the management of the current pandemic and in vaccine development against Covid-19. Importantly, the team showed that patients who recovered from SARS-CoV 17 years ago after the 2003 outbreak, still possess virus-specific memory T cells and displayed cross-immunity to SARS-CoV-2. One hypothesis is that these T cells might help give people a level of cross-immunity protection from Covid-19 because they remember previous infections by other viruses in the same family, four of which cause common colds. This could explain why some individuals are able to better control the infection, said Professor Antonio Bertoletti, from Duke-NUS, who is the corresponding author of this study.
Researchers tracking mutations in this virus have reported around 200 mutations till date. Scientists have warned that a mutation called D614G in the Spike protein region of the SARS-CoV-2 is of urgent concern, as it makes the virus more contagious. It may be pointed out that SARS- CoV-1 mutated and disappeared from the scene. Thus, a study of SARS-CoV-2 infection in different populations and at various times during the pandemic, would be an important way of understanding the dynamics of transmission and vaccine development.
(Professor, Department of Biochemistry, NEHU. Email: [email protected])