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This is Why You May Feel More Significant Side Effects from your Second Dose of the COVID-19 Vaccine

It’s a sign that your immune system is properly functioning

Royalty-free photo by Tang Ming Tung on

Side effects are a natural part of vaccination. Some individuals have reported feeling more significant side effects from their second shot compared to their first, and the reason behind it can easily be explained using science.

The fundamental principle of vaccinations is to stimulate and train the immune system in order to retain immunological memory. Much like how the police can put up “wanted posters” to help identify a criminal, vaccinations prime the immune system to remember a pathogen (disease-causing organisms), such that if it is ever encountered again, it can be met more rapidly and with greater intensity.

This article will explore the mechanism by which these side effects arise and explain why this is a sign that your immune system is properly functioning.

What is the primary immune response?

The primary immune response occurs when you are first exposed to a pathogen. Every pathogen (eg. a virus) has identifying markers, called antigens. These antigens allow the immune system to recognise a specific virus and distinguish it from other types of viruses.

Macrophages, known as “big-eaters”, are the soldiers of the immune system — eating up any invading pathogen. They digest these pathogens and break them up into fragments in order to present the antigens on their surface.

An unspecialized naive T-cell is able to bind to the antigens presented by the macrophage. This causes the naive T-cell to become activated, differentiating and cloning itself subtypes including effector T-cells and memory T-cells. These memory T-cells are crucial in establishing long-lasting immunological memory.

effB and effT refer to T-cells that are responsible for carrying out immune defence. memT refers to memory T-cells. Treg refers to regulatory T-cells that reduce the immune response as to avoid collateral damage to your own cells. Figure created using BioRender

The effector T-cells then go on to carry out the immune response, whether it be by activating even more cells such as the antibody-producing B-cells, or engaging in cytotoxic activities, killing virus-infected cells.

Eventually, once the infection has been defeated, the immune response is downregulated by the regulatory T-cells.

What is the secondary immune response?

Upon secondary exposure to the same pathogen, the secondary immune response is both faster and more intense. This is because there are more immune cells specific to that antigen circulating in the body, allowing for faster recognition.

Rather than the antigen first needing to be presented by a macrophage, then to a naive T-cell — a memory T-cell becomes activated as soon as it encounters the corresponding antigen. It rapidly copies itself into effector T-cells, and initiates a much stronger immune response which overwhelms the virus.

Between 100–1000x more antibodies are produced by the secondary immune response, with these antibodies being more potent due to having greater affinity to the antigens. Further, these antibodies remain in the blood for a longer period of time. Overall, this means that the pathogen has little time to replicate and affect the body before the immune system unleashes a devastating counterattack.

Figure created using BioRender

So why does the second shot pack a bigger punch?

The first shot will be your first exposure to the virus, so your immune system will be caught off guard. However, memory T-cells will have been produced, so your immune system will be better prepared for the second shot.

Your body will throw everything it can at the vaccine in order to eliminate it as quickly as possible. While this more intense immune response may mean you have noticeable symptoms, they will be transient as the vaccines do not contain a live virus.

Ultimately, this is good news. It means that your immune system is working properly, producing memory T-cells and retaining immunological memory. If you ever are infected with the real deal, your body will be much better prepared.

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