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Influenza Defense

The respiratory tract mucosa is the site of infection for influenza viruses and the site of defense against many other virus infections. Influenza A viruses are classified by identifying two surface proteins: Haemagglutinin (15 known forms) and Neuraminidase (9 forms).

An H1N1 virus caused the deadly 1918 pandemic. A H1N1 “swine flu” emerged in Mexico in 2009 was a new H1N1 virus. The avian flu that generated so much concern and speculation beginning in 2004 was a H5N1 version.

Genetic sequencing of viral DNA provides a more detailed method of identification. The 2009 Mexican strain contained DNA from four different virus sources: from North American swine influenza viruses, North American avian influenza viruses, human influenza viruses and swine influenza viruses found in Asia and Europe. The popular description “swine flu” was misleading since the novel DNA suggested that the viral DNA came through human and/or bird infections. Influenza viruses evolve quickly through mutation and DNA recombination.

Viruses are initially detected and destroyed non-specifically by innate immune mechanisms, but if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune mechanisms:

(i) Specific secretory-IgA (S-IgA) antibodies and CD8 cytotoxic T lymphocytes are involved in the recovery from influenza following viral infection of mice.

(ii) Preexisting specific S-IgA and IgG Abs in the immunized animals are involved in viral elimination by forming virus-Ig complexes shortly after re-infection. S-IgA Abs are carried to the mucus by transepithelial transport and provide protection against virus infection. IgGs move from the serum into the mucosa by diffusion and are distributed on the alveolar epithelia to prevent influenza pneumonia.

(iii) In the absence of Abs in the pre-immunized animals, the production of specific IgA and IgG Abs by B memory cells is accelerated after re-infection. These antibodies play a role in viral elimination from day 3 onwards after re-infection.

(iv) In the pre-immunized animals, CTL production by memory T cells is also accelerated and these cells appear to participate in the killing of the host cells infected with different subtype viruses from day 3 onwards after re-infection.

(v) Memory Th1 cells mediate an accelerated delayed-type hypersensitivity response and block virus replication by secreting IFN-gamma.

These defense mechanisms suggest that a mucosal vaccine, capable of inducing S-IgA Abs, may provide cross-protection against variant viruses within the same subtype. In addition serum IgG Abs are needed to prevent influenza pneumonia and CTLs, will provide broad cross-protection against different subtype viruses.