Innate & Adaptive Immunity

Mammals have two distinct, but interrelated immune tiers in place- the primitive innate immune system, which they share with other vertebrates, and the much more evolved adaptive immune system. When the body is invaded by foreign pathogens such as bacteria or viruses, it is the innate immunity that kicks in first- this is a generic system, geared to kill pathogens in general, and lacks specificity. Meanwhile, the much more specialised adaptive immune system recognises the specific antigen and somewhat later, mounts a deadly directed assault which, more often than not, wipes out the pathogens.

An example of the workings of both innate and adaptive immunity can be found with the human immune response to viruses. Viruses lack the capacity to make their own protein, such as the one that constitutes their coat. They can only do so by invading host cells, incorporating their own RNA or DNA into the host genome and getting the host to make the viral proteins.

When viruses first attack mammalian cells, they alter certain glyco-proteins present on the cell surface called MHC Class I molecules. These are present on all cells. Viruses downgrade or alter the production of MHC class I molecules with a rather clever motive-these molecules are essential for the next step of the host defence- the adaptive immunity. However, a member of the innate immune system, called Natural Killer cells, or NK cells, has been put in place for just such an eventuality. The NK cells recognise the cells that have altered or diminished MHC class I molecules on their surface and directly kill them by releasing enzymes called granzyme and perforin, which cause the virus infected cell to die in an orderly fashion, called apooptosis. This process is highly directed, so that neighbouring cells don't suffer. Neighbouring healthy cells are also protected by increasing their expression of MHC class I molecules due to the influence of a group of soluble agents called Class I interferons- comprising alpha and beta-interferons. Although many cells produce these two interferons, the principal source are a group of cells called plasmacytoid dendritic cells, which produce 1000 times more class I interferons than any other cells. These interferons upregulate the production of MHC class I proteins by normal cells, thus protecting them from attack by NK cells. They also produce a distinct type of interferon themselves, called interferon-gamma, which facilitates later responses by the adaptive immune system, specifically by activating a class of T-cells called Th1 cells.

For those viruses which manage to evade the NK cells and survive in host cells, backup is required. Enter the cytotoxic T lymphocytes. T cells, or thymus derived lymphocytes, are broadly of 2 types- CD4 and CD8, and form pillars of the adaptive immune system. CD8 lymphocytes, also called cytotoxic lymphocytes, recognise specific foreign antigens, mainly viral, presented on MHC class I molecules by infected cells. (thus they work in an exactly opposite way to NK cells, which recognise cells with low levels of MHC class I molecules). Cytotoxic, or CD8 lymphocytes, kill in exactly the same way as NK cells, by releasing the same destructive enzymes onto the surface of the virus infected cell in a directed way, but being part of the adaptive immune system, they are much more specific. Instead of generically killing any virus infected cell, they recognise a specific virus as it sits within a host cell. They are thus much more specific and powerful killers than NK cells. Mice lacking MHC class I molecules tend to be overwhelmed by viruses, as CD8 cells require MHC class I molecules to recognise their specific viral targets.

We'll talk more about the interplay between the innate and adaptive immune systems in later posts.