The role of dendritic cells in immunity to influenza virus.

What is influenza?
The “Spanish flu” is one of the few pandemics that killed over 20 million people around the world in 1918, and the cause is due to the influenza virus. Influenza is a contagious respiratory illness caused by RNA viruses of the family Orthomyxoviridae, and they are intracellular obligate parasite which meant they cannot replicate without a living cell (Kimball, 1994). There are 3 types of influenza viruses; influenza A is the most common and fatal disease causing viral, influenza B can also cause epidemics but are milder than type A, and lastly influenza C only causes mild respiratory infections similar to that of common cold. In healthy individuals, influenza infections are usually asymptomatic and cleared by the immune response within days. For immuno-compromised individuals such as the old and young, the symptoms could be fever, cough, sore throat, chills and headache, and in severe cases causes pneumonia that is fatal. The main cause of a pandemic is due to antigen shift where the genes encoding for H and N proteins were reassorted when viruses of 2 different subtypes were in the same cell. Epidemic is due to antigenic shift where evolutionary accumulation of new antigens or spontaneous mutations in gene gives selective advantage to a new strain when populations are getting immune to the older strain (Brankston et. al, 2007).

What are dendritic cells?
Dendritic cells (DCs) are one of the few phagocytic cells of the immune system, and they reside in many tissues, continuously sampling their environment by endocytosis, macropinocytosis, and phagocytosis. There are 2 broad classes of DCs; conventional dendritic cells (cDC) that participate in antigen presentation and activation of naïve T cells, and plasmacytoid dendritic cells (pDC) that generates large amount of signalling molecules such as IFN. Monocyte derived lineages (pDC1) stimulate Th1 cell differentiation while plasmacytoid (lymphoid) dendritic cells (pDC2) induce Th2 cell differentiation (Liu et. at, 2001). Similar to macrophages, DCs can degrade phagocytosed pathogen but this is not their main role in the immune system. The key role of DCs is to initiate an immune response whereby immature DC takes up pathogen by endocytosis. The DCs matures and thus function as Antigen Presenting Cells (APC) (Cella et. al, 2000).

Role of DCs in response to virus
When DCs make contact with foreign particles, they up-regulate expression of co-stimulatory molecules, MHC, adhesion molecules on its surface, and down-regulate ability to internalize antigens while migrating to secondary lymphoid organs such as spleen and lymph nodes. At these locations, the DC matures and presents the pathogenic antigens to naïve T lymphocytes in a form that it recognises (Banchereau & Steinman, 1998).
DCs play a crucial role in the immunity against influenza virus as they are efficient stimulators of B and T lymphocytes. As we know, both antibodies and T cells are critical in the immune responses towards foreign particles such as the influenza virus. B cells are antibody producing cells are responsible for humoral immunity. They can recognise foreign antigens directly by their B cells receptors. T cells, on the other hand, require APC (such as dendritic cells) to present antigens that have been processed before the T lymphocytes are able to recognise them. It is evident that the ability of DCs acting as an Antigen Presenting Cells (APC) is important in the initiation of the adaptive immune response towards influenza virus (Bhardwaj et. al, 1994).
T cells receptors (TCR) will recognise antigen presented on MHC class I and MHC class II on the APC, which will then stimulate naïve CD8+ cytotoxic T cells and CD4+ Helper T cells respectively. When naïve CD8+ cytotoxic T cells and its co-stimulatory receptor are activated by the recognition of MHC class I and co-stimulatory molecules, it will mature into Cytotoxic