With the emergence of the SARS-CoV-2 pandemic, science and humanity have been faced with several new challenges and obstacles. Less than a year passed from the first quarantines to the development of the vaccine, and medicine progressed at an incredible rate. With the emergence of new variants of the virus and the growing number of deaths from COVID-19, scientists have embarked on a detailed evaluation of the human body's immune response to the SARS-CoV-2 infection. From the moment the virus enters the cell via ACE2 receptors, the mechanisms of the innate immune system are triggered and numerous cells such as neutrophils, macrophages, dendritic cells, basophils and eosinophils are activated. Large amounts of chemokines and cytokines are secreted that recruit immune system cells to the site of infection. Only 7 days after the infection, antibodies are directed against infected cells that prevent the virus from further entering the host cells by binding to the S protein. In parallel with the innate immune system, cellular immunity is activated and CD4 + and CD8 + T lymphocytes interact with the purpose of destroying infected cells. This is followed by a phase of resolving the disease and creating an acquired immunity that protects against further reinfections. It has long been thought that antibodies produced by the plasma cells are responsible for this, but today it is believed that this role belongs to CD4 + T lymphocytes. These cells have shown cross-reactivity with SARS-CoV-2 in non-exposed individuals, and their response to vaccination against SARS-CoV-2 gives a very violent reaction where large amounts of cells are formed that remain present in our body for up to 9 months. It is also thought that these cells could be a key answer to the question of why the elderly population is more susceptible to SARS-CoV-2 infection and why they have poorer disease outcomes. Their role and importance in long-term immunity against SARS-CoV-2 and other types of HCoV in healthy individuals is not fully known to date but is a current topic of numerous studies.