Question

Describe the innate immune responses to COVID-19 infection. Be sure to include the IFN response, and the innate immune cells responding to viral infection (and the mechanism how the do it). In addition, include the “cytokine storm” induced by COVID-19; you can find this information in the article “Covid-19 and immune system, 2020”.

Answer 1

• Immune response is initiated when; the body encounters the virus (human pathogens include mainly alpha and beta), whose surface proteins interact with the components of immune system (acting as antigens CoV-like: Membrane protein M, N or nucleocapsid protein, envelope E, etc.)

• The innate immunity or non-specific immunity acts as the first line of defense, provides barrier against the foreign substances.
• The cell receptors detecting Cov antigens include Toll like receptors (TLR-3, TLR-7) and pattern recognition receptors.
• Various cytokines released from specific cells, like interleukins (IL), tumor necrosis factor alpha (TNFα), activates the production of mature phagocytic cells, like neutrophils, macrophages and dendritic cells and induce their migration to the site of infection or invasion.
• Phagocytic cells, engulf the foreign substances by phagocytosis or endocytosis.
• The phagocytosed molecules processed and, then the peptide fragments of antigens are expressed through membrane bound glycoproteins called major histocompatibility complex (MHC).

• The major cytokines that play an important innate immune response against the viral replication, are the interferons.
• For covid viruses, Type I interferons are observed to be eminent.
• Type I-includes INFα, β, ε, κ, and ω.
• IFNs mainly act as antiviral agents, induces production of protein kinase R (PK R), causes apoptosis of viral infected cells.

• Further, lineages of T-cells are activated.
• Mjorly the T-cell sub-type TH -17 are activated by CoV antigens.
• These cells help to stimulate epithelial cells to produce antimicrobial substances to aid to physiological barrier of innate immunity.
• Also helps in migration of neutrophils to site of infection.
• Further various cytokines released include: IL-1, IL-6, IL-8, IL-21, TNF-beta and MCP-1.

• These cytokines act as signalling cascades to further activate other pahgocytic cells (dendritic cells and macrophages), adaptive immune response.

• The inteferons stimulate various natural killer cells. Natural killer (NK) cells–play important role in recognition and elimination of tumor and virus infected cells. NK cells recognize such cells by distinguishing major histocompatibility complex (MHC) molecules on abnormal cells. NK cells may also detect the target cells by process of antibody dependent cell mediated cytotoxicity (ADCC).

• However several NK cells (NK k-B) may further generate a proinflammatory response a create a " cytokine storm".
• This may result in profuse inflammatory rsponses causing respiratory damages.
• Thus, antiinflammatory treatmnets with hydrochloroquine, or Interleukin anatagonist drugs may be implemented.