COVID-19 immunology 101 for non-immunologists by Akiko Iwasaki, Ph.D. (English)

Overview

Hello. This is Professor Akiko Iwasaki. I'm an immunologist. I often hear questions like “What is the difference between antibody and immunity?”. With the help from BioRender, I've put together immunology 101, a tutorial for non-immunologists. 

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The immune system protects the host organism from invading pathogens like viruses, bacteria, fungi, and parasites. To do so, the immune system employs 2 layers, DNA and adaptive immunity. Innate immunity acts within minutes of infection to remove the pathogen. This is a nonspecific short term solution. In parallel, innate immune cells induce activation of the inactive immune system. This takes a week or two to get going, But once established, the adaptive immunity provides long term pathogen specific defense for the host.

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So let's dive a bit deeper. Innate immunity starts by detection of microbial pathogens, to sensors that detect unusual molecules or activities known as pattern recognition. Once microbial patterns are detected by these sensors, they trigger immediate alarm through the secretion of cytokines and interferons. Cytokines and interferons bind to their receptors on various cells around them to help put up guard against further invasion. They also induce death of infected cells, so as to stop further spread of the virus.

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Finally, interferon cytokines also induce another set of signals that flag white blood cells to be recruited to the site of infection, to wall off and attack the invaders.

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However, when cytokines are triggered without breaks, they can cause damage to the cells responding to the cytokines and shut down the function of the organs. This is known as cytokine storm, which mediates severe disease including COVID-19. During SARS CoV-2 infection, the virus infects and replicates in the lung epithelial cells. The virus is detected by macrophages through pattern recognition receptors, which trigger the secretion of interferons and cytokines. However, this virus appears to be oblivious to the interferons antiviral effects. Instead, the cytokines recruit more white blood cells, to swarm the tissue, creating a cytokine storm, where many cells contribute to the secretion of lots of different cytokines.

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Some of these cytokines include those that induce fibrin deposits as well as damage the blood vessels for fluid to leak out into the alveoli, causing respiratory failure. Viruses block the secretion and function of cytokines and interferons so that they can replicate and spread by evading the host innate defense system. When this happens, the body starts the second layer of immune system, the adaptive immune response. The T and B lymphocytes, the key players of the adaptive immune system, require education by dendritic cells. Dendritic cells are specialized white blood cells that survey the tissue for potential pathogens.

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Once dendritic cells detect pathogens through their pattern recognition receptors, they not only secret cytokines, but are also signal to migrate to joining lymph nodes.Naive uneducated T and B cells sitting in the lymph nodes interact with dendritic cells.

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If their receptors happen to match the antigen presented by the dendritic cells, they become activated, expand and become so called effector lymphocytes. These effector lymphocytes migrate back to the site of infection and directly kill infected cells and block further viral spread by secreting specific antibodies. These specialized white blood cells, T and B cells, are called into action by antigen presenting cells.

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Once they reach the target tissue, T cells trained into killer soldiers detect specific virus fragments on the surface of infected cells and destroy them, eliminating the source of the viral factory. Antibody secreted by B cells bind to the surface of the virus and block their entry into host cells. These are called the neutralizing antibodies. B cells also secrete non neutralizing antibodies that call in other white blood cells such as natural killer cells to kill virus infected cells.

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Natural killer cells are professional killer cells, but need guidance from antibodies to target their weapons against the infected cells. What's cool about the adaptive immune system is that both T and B cells become memory cells and provide immune defense for a long time.

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Memory T and B cells survive for years and are able to defend against the same pathogen during second exposure much better than the untrained lymphocytes. So the second time you encounter the same virus, your memory B cells will quickly stimulate to produce much higher levels and quality of antibodies. Similarly, memory T cells provide quick and robust protection especially if they're within the sight of virus entry. Some B cells become plasma cells, which secrete tons of antibodies for years.

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If you were vaccinated as a child, you are likely to have antibodies to the vaccine antigens decades later. Antibodies will bind to the invading pathogen immediately and block their further spread.

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Serological assays detect the level of antibodies to various pathogens and is a good indicator of your previous exposure to pathogen or vaccination. How long the antibody lasts depends on the type of pathogens; measles antibodies last for decades, for common cold coronaviruses, 1 to 2 years. However, you still have memory B cells and T cells that can reignite antibody and killer cells during the second exposure. You're still much better off than when you were naive to the pathogen.

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However, the safest and the most reliable way to achieve immunity is through vaccination. Vaccines are designed to trigger robust and long lasting immunity, superior to that achieved by natural infection. It is the only safe way to develop herd immunity. Herd immunity refers to the protection achieved at the population level if enough people are immune to a given pathogen.

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For highly infectious viruses like SARS CoV-two, the majority of people in the population must be immune in order to confer protective herd immunity against those who are not yet immunized. There are over 100 vaccine candidates against SARS CoV-2.

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We hope that some of these will provide durable and effective immunity. Mediated by both antibodies and T cells to help us stop the spread of COVID-19. Thank you for listening.

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