Question

Type a 500-600 word response to this topic to be submitted for assessment:

While an immune response to a pathogen such as a Covid 19 will involve many features of immunity we have learn about, a critical aspect will be the T cell response. T cells, once activated can differentiate into one of the various effector T cell subsets that are known and in particular to this conversation, the CD4 T subsets, Th1, Th2 and TH17 cells and the CD8 cytotoxic T cell subset.

Now focusing mostly on the adaptive T cell immune response to a viral infection, describe the key immunological events that would occur upon infection with a virus (generic) that would lead to a effective cytotoxic T cell response and how this would assist in clearing the virus.

Answer 1

ADAPTIVE IMMUNE TCELL RESPONSE TO VIRAL INFECTION:

ENTRY OF VIRAL PATHOGEN:

Innate Response:

The principal barriers in a viral infection between the host and the environment are the epithelia of the skin and the gastrointestinal and respiratory tracts. If microbes are able to traverse these epithelia and enter tissues and circulation , they encounter the defense mechanisms of Innate immunity in the form of phagocytes, macrophages , dendritic cells, Natural Killer cells which causes inflammation and antiviral defense. In addition to combating the viral infections, innate immune responses stimulate adaptive immunity providing signals that are essential for initiating the responses of antigen specific T and B lymphocytes.

CAPTURE AND DISPLAY OF MICROBIAL ANTIGENS:

• Microbes that enter through epithelia are captured by dendritic cells and the cell bound antigens are transported to draining lymph nodes.
• The antigens are displayed on the surface of the Antigen Presenting Cells (APCs) bound to MHC molecules.
• Native T cells recognize these peptide MHC complexes which is the first step in the initiation of T cell responses and T cells undergo differentiation.
• Signals generated in lymphocytes by the engagement of antigen receptors lead to transcription of various genes encoding cytokines, effector receptors and proteins that control cell survival and cycling.

CELL MEDIATED IMMUNITY:

• When activated by antigens and costimulators in lymphoid organs, naive T cells secrete cytokines that function as growth factors and respond to other cytokines secreted by APCs.
• The combination of signals stimulates the proliferation of T cells and their differentiation into effector T cells.
• The effector T cells generated in lymphoid organs migrate back into blood and are reactivated as effector cells.
• Helper T cells secrete cytokines and express surface molecules that mediate their functions.
• The activated T helper cells function to recruit neutrophils and other leukocytes to the sites of infection whereas other helper cells activate macrophages to kill ingested microbes, other cells stay in lymphoid organ and help B cells.
• CTLs directly kill cells harboring microbes in cytoplasm. By destroying the infected cells, CTLs eliminate the reservoirs of infection.

ROLE OF CYTOTOXIC T LYMPHOCYTES (CTL):

The best understood function of CD8 T cells is of CTL effectors. CTLs are particularly important in host defences against virus infected cells. They kill target cells which express viral peptides bound to self MHC class I molecules. The killing is unidirectional where CTL is not harmed and can detach from the target. killing is via two mechanisms: death receptor induced apoptotic mechanism and involving insertion of perforins into the target cell membrane to create a pore through which granzyme and other cytotoxic enzymes can be transferred from CTL to target cell. CTL activity is enhance by IFN - gamma cells.