Unit 12: Diseases and Infections
D: Understand how the human body responds to diseases and infections
Human immune responses
Case study: Cellular and humoral immune responses of COVID-19
COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) [1]. This
virus first appeared in China and quickly spread over the world [1].
Infection with SARS-CoV-2 damages lung tissue, triggering a cell-mediated immune response [1]. Monocytes and
macrophages become activated, which release inflammatory cytokines and stimulate specific T- and B-cell responses
[1]. Inflammatory cytokine levels, monocytes and macrophages can produce septic shock and multiorgan failure;
this may explain why some individuals exhibit cardiac injury and circulatory failure [1]. CD8+ T-cells attack
virus-infected cells directly and release cytokines that attract immune cells to the site of infection [1]. This is a
benefit of the cell-mediated response since it helps to eliminate the virus at the cellular level. CD4+ T-cells help
B-cells produce antibodies and prime the response of CD8+ T-cells and other immune cells [1]. This guarantees that
the defence is well-coordinated. Depending on the time, components and/or amplitude of the induced immune
response, the immune response might be either protective or pathogenic [1]. T-cells and B-cells are long-term
immunological memory cells [1]. This is beneficial since both types of cells will provide protective immunity against
future SARS-CoV-2 infections [1]. However, specific immune responses to coronavirus may fail and protective
immunity may not develop [1]. Failure to develop long-term immunity could be related to insufficient CD4+ T-cell
response and insufficient neutralising antibody response [1]. Regulatory T cells (Treg) are present to keep
inflammation under control [1]. Treg cells are either produced from the thymus or created in the periphery to
establish immunological tolerance [1]. Contrastingly, individuals with severe Covid-19 have lower levels of peripheral
Treg cells than individuals with moderate illness [1]. Although the causes for this decrease in Treg cells are unknown,
it is likely that the cells are migrating to the location of inflammation in the lung to protect tissue [1]. Studies have
shown that Treg cells significantly help to treat acute respiratory distress syndrome (ARDS) inflammation in animals.
The fact that they can reduce ARDS in animals suggests that they can also help to alleviate lung damage in humans
caused by COVID-19 [1].
Humoral immunity produces an immune response through antibodies (such as monoclonal antibodies), each of
which are specific to a certain antigen that neutralise the SARS-CoV-2 virus [1]. Neutralising antibodies primarily
target the receptor binding domain (RBD): a 193 amino acid region of the spike protein that interacts with the ACE2
receptor [1]. The use of previously identified monoclonal antibodies developed for SARS-CoV gives a potential
benefit in taking advantage of present knowledge and methods for the development of SARS-CoV-2 treatments [1].
While certain antibodies can attach to both viruses, deviations in the RBDs can cause variation in epitope specificity
[1]. Several powerful SARS-CoV neutralising antibodies do not bind to SARS-CoV-2; this is most likely due to
differences in the RBDs [1]. This is a disadvantage of the humoral response as this finding implies that not all
previously successful antibodies can be used to tackle various strains of the virus. Antibodies generated against
SARS-CoV can cross-react and neutralise SARS-CoV-2; this suggests that the two viruses have overlapping epitopes,
even though only 15 of the 33 conserved amino acids in the spike protein region essential for ACE2 binding are
conserved [1]. The fact that the antibodies generated against SARS-CoV can cross-react with and neutralise
SARS-CoV-2 implies a degree of adaptability and flexibility in the immune response, potentially conferring some level
of pre-existing immunity or an increased response. However, certain antibodies against both viruses may be less
effective as a result.
Overall, the humoral immune response is stronger against COVID-19 because of the fast responses produced by
antibodies. The humoral immune response can produce long-term immunity in an individual, whereas the
cell-mediated response has the ability to fail occasionally due to inadequate CD4+ T cell responses.
D: Understand how the human body responds to diseases and infections
Human immune responses
Case study: Cellular and humoral immune responses of COVID-19
COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) [1]. This
virus first appeared in China and quickly spread over the world [1].
Infection with SARS-CoV-2 damages lung tissue, triggering a cell-mediated immune response [1]. Monocytes and
macrophages become activated, which release inflammatory cytokines and stimulate specific T- and B-cell responses
[1]. Inflammatory cytokine levels, monocytes and macrophages can produce septic shock and multiorgan failure;
this may explain why some individuals exhibit cardiac injury and circulatory failure [1]. CD8+ T-cells attack
virus-infected cells directly and release cytokines that attract immune cells to the site of infection [1]. This is a
benefit of the cell-mediated response since it helps to eliminate the virus at the cellular level. CD4+ T-cells help
B-cells produce antibodies and prime the response of CD8+ T-cells and other immune cells [1]. This guarantees that
the defence is well-coordinated. Depending on the time, components and/or amplitude of the induced immune
response, the immune response might be either protective or pathogenic [1]. T-cells and B-cells are long-term
immunological memory cells [1]. This is beneficial since both types of cells will provide protective immunity against
future SARS-CoV-2 infections [1]. However, specific immune responses to coronavirus may fail and protective
immunity may not develop [1]. Failure to develop long-term immunity could be related to insufficient CD4+ T-cell
response and insufficient neutralising antibody response [1]. Regulatory T cells (Treg) are present to keep
inflammation under control [1]. Treg cells are either produced from the thymus or created in the periphery to
establish immunological tolerance [1]. Contrastingly, individuals with severe Covid-19 have lower levels of peripheral
Treg cells than individuals with moderate illness [1]. Although the causes for this decrease in Treg cells are unknown,
it is likely that the cells are migrating to the location of inflammation in the lung to protect tissue [1]. Studies have
shown that Treg cells significantly help to treat acute respiratory distress syndrome (ARDS) inflammation in animals.
The fact that they can reduce ARDS in animals suggests that they can also help to alleviate lung damage in humans
caused by COVID-19 [1].
Humoral immunity produces an immune response through antibodies (such as monoclonal antibodies), each of
which are specific to a certain antigen that neutralise the SARS-CoV-2 virus [1]. Neutralising antibodies primarily
target the receptor binding domain (RBD): a 193 amino acid region of the spike protein that interacts with the ACE2
receptor [1]. The use of previously identified monoclonal antibodies developed for SARS-CoV gives a potential
benefit in taking advantage of present knowledge and methods for the development of SARS-CoV-2 treatments [1].
While certain antibodies can attach to both viruses, deviations in the RBDs can cause variation in epitope specificity
[1]. Several powerful SARS-CoV neutralising antibodies do not bind to SARS-CoV-2; this is most likely due to
differences in the RBDs [1]. This is a disadvantage of the humoral response as this finding implies that not all
previously successful antibodies can be used to tackle various strains of the virus. Antibodies generated against
SARS-CoV can cross-react and neutralise SARS-CoV-2; this suggests that the two viruses have overlapping epitopes,
even though only 15 of the 33 conserved amino acids in the spike protein region essential for ACE2 binding are
conserved [1]. The fact that the antibodies generated against SARS-CoV can cross-react with and neutralise
SARS-CoV-2 implies a degree of adaptability and flexibility in the immune response, potentially conferring some level
of pre-existing immunity or an increased response. However, certain antibodies against both viruses may be less
effective as a result.
Overall, the humoral immune response is stronger against COVID-19 because of the fast responses produced by
antibodies. The humoral immune response can produce long-term immunity in an individual, whereas the
cell-mediated response has the ability to fail occasionally due to inadequate CD4+ T cell responses.
