Short Answer Part 1 1. In what ways can viruses evade the immune system? Which o

Question

Short Answer Part 1

1. In what ways can viruses evade the immune system? Which of these strategies leads to chronic infection and why?

2. How does an infection by HIV cause AIDS?

3. What are some immunodeficiencies that primarily affect T lymphocytes? Why do you think these generally affect immune responses more severely than deficiencies involving B cells only?

4. Compare and contrast antigenic shift and antigenic drift. How do these types of antigenic variation occur?

5. We are exposed to foreign antigens in large quantities in the food that we eat. Why do we not mount effective immune responses against these food antigens?

Explanation / Answer

1. Given below are some of the strategies a virus can employ to evade the immune system:

a) Downregulation of surface MHC class I molecules. This way cells infected by virus cannot be recognized and killed by Cytotoxic T-Lymphocytes (CTLs), which are MHC class I restricted.

b) By deceiving Natural Killer Cells (NK). NK cells can recognize and clear cells which are deficient in self-MHC class I expression. But viruses can fool these NK cells by expressing homologs of MHC class I molecules (eg. Cytomegaloviruses) which serve as decoy receptors for NK cells.

c) Negative Regulators of Cytokines. Cytokines are chemicals messengers of the immune system which can both positively as well as negatively regulate immune responses. Viruses can express homologs of negative cytokines, eg. Epstein Barr Virus codes for homolog of IL-10 which negatively regulates IL-12.

d) Inhibition of apoptosis. Viruses induce apoptotic response in infected cells so that the cells are killed before virus replicates inside them and produces progeny virions which will help in spreading of the infection in neighbouring cells.

Although every evasion mechanism will lead to chronic infection in some or the other way, out of the above strategies a), b) and d) will have a more direct way in making the infection chronic as all these strategies will eventually help the virus to persist in the body for long duration.

2. HIV invades cells which express CD4 marker (T-Helper cells) through interaction with a glycoprotein present on its envelope. The single stranded RNA of the virus gets converted into double stranded DNA and gets integrated into the genome of the infected cells. The infection can remain latent for very long (upto 10 years). When viral elements are finally expressed in the cells they will eventually lead to release of progeny virions killing the host cells. With time, more and more CD4+ cells are attacked and killed by the virus compromising the immune system of the individual. Such people are not able to mount infection against opportunistic infections (which do not show in individuals with strong immune system) and develop AIDS in later stages with characteristic infections like cryptococcal meningitis and Kaposi's sarcoma.

3. Immunodeficiences affecting primarily T cells are: AIDS, Omenn syndrome, Cartilage hair hyoplasia, lymphoma.

The specific function of recognising MHC-peptide complexes presented on Antigen Presenting Cells and mounting cell mediated response by T cells eventually leads to the activation of B cell proliferation. Through this crosstalk T cells are partly responsible for B cell mediated immune response also, so if T cells are eliminated both the branches of adaptive immune system willl be hampered and the immune responses will be affected more severely than it will be in the case of B cell immunodeficiency.

4. Antigenic shift is the creation of a new strain of a virus by reassortment of viral genes from two different strains, such process leads to the ability of the new strain to infect two different organisms. Whereas antigenic drift is the process of creation of new strains of virus by natural genetic changes that accumulate with time.

Let's consider the example of Influenza A. Different strains of Influenza A infect different hosts, say human and bird. The virus can get transmitted to an intermediate host (pig) from both human and birds. When same cells in the intermediate host get infected with both kinds of strains, exchange of genes while virion assembly gives rise to a new strain with genes from both the parental strain and this strain is capable of directly jumping from bird to human or vice versa.

Antigenic drift can be seen in Influenza A, B and C. It helps the virus in evading host immune responses by mutations occuring in components of the virus that are targets for host antibodies. Specific sites recognized by antibodies on Hemagglutinin and Neuraminidase surface protein of Influenza virus are under selective pressure and small mutations in them help in evading cellular responses.

5. Food antigens, in particular proteins that we eat, are digested into smaller peptides that may be further broken down into single amino acids which are not immunogenic. Component of a protein recognized by our immune system (epitope) is a series of amino acids arranged in a particular sequence which can be continuous or discontinuous. Such epitopes are lost when a protein is denatured or broken down, thus immune responses are not usually mounted against food. Exception: food allergies.

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