What does the immune system do?
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A virus hijacks a cell to replicate itself. There is more than one way in which our immune systems can defend us from them. Our bodies have developed sophisticated defence mechanisms to protect us. This article explores how our immune system combats viral infections and the unique challenges presented by cells containing mRNA from vaccines.
First Line of Defence: Blocking Entry
Before a virus can invade our cells, such as when a respiratory virus is still in the airway, the immune system employs several non-antibody defences to intercept it. Physical barriers like skin, mucus and chemical defences in saliva and stomach acid, act as the first line of defence to block or destroy pathogens. Innate immune cells, such as macrophages and dendritic cells, can directly attack invading viruses. The complement system enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, while interferons are released by infected cells to warn neighbouring cells and inhibit viral replication. Additionally, cytokines orchestrate an effective inflammatory response, recruiting immune cells to the site of infection.
In addition to these robust mechanisms of defence the body can mount a specific attack which also prevents entry into the body through making specialised antibodies on the mucosal surface e.g. inside the airways. These antibodies latch onto the virus, marking it for destruction by other immune cells, effectively stopping the virus in its tracks before it can even enter our bodies.
Second Line of Defence: Natural Killer Cells
Natural Killer (NK) cells are a crucial part of our immune defence, identifying cells infected by viruses with remarkable efficiency. They do this by detecting unusual signals which include among others the formation of endosomes—small vesicles that viruses use to enter cells—and the presence of double-stranded RNA, a telltale sign of viral replication. These signals indicate that a cell has been compromised and prompt NK cells to eliminate it, thereby preventing the virus from multiplying and spreading.
For most people we can stop there. The specific immune system barely ever comes into play. In severe cases it can be relevant. In the words of Fauci et al, respiratory viruses “replicate predominantly in local mucosal tissue, without causing viremia, and do not significantly encounter the systemic immune system or the full force of adaptive immune responses, which take at least 5–7 days to mature, usually well after the peak of viral replication and onward transmission to others.”
Third Line of Defense: T Cells
Every cell in our body displays bits of the proteins it’s making on its surface. Every cell in our body displays on its surface fragments of the proteins it is making regardless of where the protein is expressed. T cells check these fragments and if they match something on the police database they attack. When a cell starts producing foreign proteins due to a viral infection, T cells are activated. One type, CD8 cells, directly destroy the infected cells. Another type, CD4 cells, memorise the viral protein for a faster response in future encounters. Both the CD8 and CD4 cells depend on the judicial system of the lymph nodes which ensures the protection of our own innocent proteins. This system ensures that cells displaying foreign (viral) proteins are targeted and eliminated.
However, viruses like SARS-CoV-2 have evolved mechanisms to evade this response. The virus can, (via activating a particular pathway) induce infected cells to express a molecule called PD-L1, which interacts with T cells, signalling them not to attack the infected cell.
Fourth Line of Defence: Antibodies and the Membrane Attack Complex
Blood borne antibodies bind to the fragments on display tagging an infected cell and triggering cell death via Natural Killer Cells or activating a chemical cascade that leads to holes being punched into the cell membrane via a “Membrane Attack Complex.”
Anyone wanting to make a fair assessment of a claim of enhancing the immune defence to a virus would focus on the effect on the T cells. Was it educated correctly and primed to remember in advance of an infection? Pfizer/BioNTech attributed the immune response to “other immune mechanisms” including T cells, because they claimed an impact after 11 days whereas the antibody response wasn’t adequate until day 28. However, throughout the first half of the 2020s the antibody levels have been used as a measure of vaccine success.
The end result of a viral infection is therefore cell sacrifice. For SARS-CoV-2 the vast majority of cells sacrificed are mucosal cells lining the respiratory tract. These have a high turnover and will be rapidly replaced as with all cells that form a function as a protective barrier. Except in the very sick, viruses remain restricted to the respiratory lining during an infection. Positive PCR from blood is often a result of circulating viral RNA rather than circulating intact virus capable of infecting other cells.
The story with the covid mRNA vaccines is different:
Firstly, it’s worth considering what happens to foreign mRNA in a cell. In a healthy cell every component is part of a complex dance and the production of a new protein is carefully guided with so called chaperone proteins to take the new protein to where it is needed. That might be the nucleus, elsewhere in the cytoplasm, the cell surface or outside of the cell. Where the protein being produced is foreign any – or more than one – of those outcomes is possible. There is evidence of large quantities of cell membrane bubbles, called exosomes, containing spike protein circulating in the blood for at least 4 months after injection. The antibody levels rose and fell in line with these circulating exosomes. However, there is also evidence of a post vaccine active T cell population responding to spike protein suggesting continuing display of spike fragments at the cell surface.
First Line of Defence: Blocking Entry
First of all the delivery system is such that there is no opportunity for the immune system to prevent cell entry. The vaccines are delivered in lipid nanoparticles directly into the body with no proteins on their surface for antibodies to bind to.
Second Line of Defence: Natural Killer Cells
The lipid nanoparticles merge with the cell membrane to deliver the mRNA into the cell. There is therefore no indication of cell invasion like the viral endosomes to alert Natural Killer cells. Similarly there is no double stranded RNA to alert Natural Killer cells as there is no replication.
Third Line of Defense: T Cells
Thankfully the system to alert T cells to kill the cell still functions. However, the spike protein from the vaccine can also result in the cells hiding from T cells using the PD-L1 receptor (as described above).
Fourth Line of Defence: Antibodies and the Membrane Attack Complex
Blood borne antibodies can continue to bind to infected cells leading to cell destruction.
The different methods of cell death have different outcomes for neighbouring cells. Immune defence 1-3 results in tidy destruction of a single cell. However, immune defence 4 where antibodies bind to cells and where other immune cells are involved can potentially lead to more inflammation and collateral damage to surrounding tissues. The Membrane Attack Complex results in rupture of the target cell which can cause inflammation and damage to neighbouring cells.
The end result should be cell death in either circumstance but the cells containing vaccine mRNA have a less watertight path to cell destruction and a path that causes more collateral damage.
