BIOMEDICAL APPLICATIONS III: DELIVERY OF IMMUNOSTIMULANTS AND VACCINES - Carbon Nanotubes: From Bench Chemistry to Promising Biomedical Applications - page 86

Once a B cell encounters a pathogen (antigen), it processes and presents
the same antigen (although not in the native shape but in a digested form,
i.e., as a peptide fragment) to special subtypes of T cells (called Th cells or
helper T cells, i.e., CD4+ T cells) through a class II MHC, thus acting as antigen-
presenting cells (APCs). This phenomenon, known as immunological synapse,
stimulates CD4+ T cells to secrete cytokines 2 that activate speciic B cells
towards the production of antibodies against the antigens. Type 1 T helper
(Th1) cells produce interferon-gamma (IFN-γ), interleukin (IL)-2 and tumour
necrosis factor (TNF)-β, which activate macrophages and are responsible for
cell-mediated immunity and phagocyte-dependent protective responses. By
contrast, type 2 Th (Th2) cells produce interleukin (IL)-4, IL-5, IL-10 and IL-13,
which are responsible for strong antibody production, eosinophil activation
and inhibition of several macrophage functions, thus providing phagocyte-
independent protective responses. Th1 cells mainly develop after infection
by intracellular bacteria and some viruses, whereas Th2 cells predominate
in response to infestations by gastrointestinal nematodes. 3 Once stimulated
by Th cells, activated B cells produce antibodies (e.g., IgG, IgA or IgE), 4 which
assist in inhibiting extraneous pathogens and neutralising viruses and
bacterial toxins. Alternatively, cytotoxic CD8 + (CTL) T cells can directly clear
virus-infected cells and regulate the immune responses to foreign antigens
on the basis of the cytokine proile they secrete via a different mechanism.
In a similar way, speciic synthetic peptides, made up of selected amino acid
sequences, represent useful tools to elicit an immunogenic response, because
they mimic crucial parts of natural proteins while avoiding the redundancy
of superluous residues. These same sequences are extremely advantageous
in the development of vaccines, because they can act as antigens (epitopes),
provided they induce the production, inside the host, of speciic antibodies
from B and T cells. In order to succeed, the native structure of the synthetic
peptide antigen should be preserved to obtain a protective antibody response.
This represents a crucial requirement in the development of vaccines, since it
is critical for recognition by antibodies.
4.2 IMMUNOGENIC RESPONSE OF PEPTIDE ANTIGENS
CONJUGATED TO FUNCTIONALISED CNTS
The development of effective delivery systems has been rapidly expanding,
because of the imperative need to target bioactive molecules and elicit the
best pharmacological proiles while avoiding side effects. Carbon nanotubes
(CNTs) have emerged as promising vehicles essentially because of their