3.2.3.2

Natural Killer Cells

APCs, described previously, deal with pathogens that can be phagocytosed, but

there are intracellular pathogens, such as viruses that are typically not phagocy-

tosed. In a typical viral infection, the virus recognizes a cellular cell surface protein,

and uses this contact to, either enter or release genetic material into the cell. The

virus then uses the cellular machinery to make progeny viruses, which are released.

So the majority of the life-cycle of the virus is spent within the cell, protected from

phagocytosis. TLRs such as TLR8 and 9 and NLRs such as RIG-1 and MDA5 can

recognize the distinct characteristics of viral nucleic acids and this recognition leads

to activation of the inflammatory pathway. In addition to virally infected cells,

abnormal cells, such as cancerous, apoptotic, or stressed cells also need to be re-

moved from the body and can be recognized by virtue of certain damage-induced

molecular patterns (DAMPs). These too are recognized and eliminated by natural

killer or NK cells.

Virus-infected cells produce interferons which activate NK cells. Upon activa-

tion, NK cells can kill target cells by releasing cytotoxic molecules such as perforin,

which perforates the membrane of the target cells and granzyme that induces

apoptosis. In addition, activated NK cells produce interferon γ (type II IFN-γ),

which stimulates other cells to orchestrate defenses against viruses and stressed or

cancerous cells.

3.3

THE ADAPTIVE IMMUNE SYSTEM

The innate immune cell types recognize the threat and convey the information to the

adaptive immune system by presenting fragments of the foreign organism to the

adaptive immune system. The relay of information takes place in the lymphatic

system, which is illustrated in Figure 3.5. It is made up of a series of vessels that

carry lymph throughout the body. Lymph, the liquid part, leaves the blood vessels

and bathes tissues, picking up any debris or foreign matter that it encounters in the

tissues, and then bringing it back to the lymph vessels.

There are also primary lymphoid organs, the organs in which the cells of the

adaptive immune system are generated. These are the thymus and bone marrow,

the sites of T and B cell production, respectively. In addition, there are the

secondary lymphoid organs, where antigen presentation takes place. The sec-

ondary lymphoid organs are the lymph nodes and the spleen. As blood goes

through the lymph node, the T-cells and B-cells leave the blood and go into the

lymph node, where they are exposed to soluble antigen that has been collected by

the lymph. As discussed, the lymph bathes the tissues, picks up whatever is in the

tissues, and brings it back to the nodes. The adaptive immune system uses two

major strategies to respond to the threat: the first, the humoral response, wherein

the response is mediated by immunoglobulins, molecules that can recognize the

pathogen with exquisite specificity and second, the cellular response, in which

T-cells play a pivotal role not only in attacking the infected cell themselves, but

also in supporting the humoral response.

40

Bioprocessing of Viral Vaccines