Biomedical Engineering Reference
In-Depth Information
diseases, allergy/asthma, inl ammation, and transplantation), agents that stimulate or activates the
immune system to work harder or smarter (virus infections and cancer), and i nally the removal of
unwanted cellular subtypes of the immune system by depletion via specii c surface antigens (auto-
immune disease and cancer).
This chapter will give an overview of the key cellular and molecular drivers of the immune
system. The following molecular approaches to treat diseases will then be covered: general immune
suppression, depletion of B cells, modulation of T cells, and i nally cytokines. Focus will be on
autoimmune diseases, inl ammation, and cancer.
22.2 BRIEF INTRODUCTION TO THE IMMUNE SYSTEM
The immune system has evolved to i ght antigens invading the human body. Antigens are nonself
entities, e.g., parts of bacteria, virus, parasites, foreign materials such as splinters and host generated
threats such as cancer. An immune response can be divided into two phases: (1) the recognition of
the antigen and (2) the elimination of the antigen.
There are two types of immune responses, namely, an innate response and an adaptive response
both capable of distinguishing between self and nonself antigens but with different mechanism
and specii city. The innate and the adaptive immune responses are interdependent and elements of
one response enhance the other. The innate response is nonspecii c and is designed to recognize
molecular patterns common to a wide variety of pathogens. On second encounter of a pathogen, the
response is exactly the same as the i rst. The response involves physical, chemical, and molecular
barriers that distinguish and exclude the antigens. The adaptive immune response involves highly
specii c recognition and effector actions involving a variety of cells in the body. Unique antigens
from the foreign entity will be specii cally recognized by receptors expressed on B and T cells and
an effector action against the entity is initiated. On second attack by the same entity, a faster and much
stronger response called a memory adaptive response is induced, which will prevent disease from
occurring the second time.
22.2.1 C
ELLS
OF
THE
I
MMUNE
S
YSTEM
The cells mediating the immune response are the leukocytes or white blood cells. The innate
immune response is constituted by (1) granulocytes, that by phagocytosis, can engulf and destroy
pathogens; (2) monocytes that can differentiate into macrophages; and (3) dendritic cells (DCs) that
are also capable of phagocytosis and secretion of cytokines and growth factors that activate T cells
in the adaptive immune system. Macrophages and DCs can present antigens to the T and B cells and
fall into the category of antigen presenting cells (APCs).
B cells and T cells are lymphocytes, and are mediators of the adaptive immune response.
Although mature lymphocytes look alike, they are diverse in their functions. B cells are produced
and mature in the bone marrow, whereas the precursors of T cells leave the bone marrow and
mature in the thymus (which accounts for their designation). The specii city of binding is dei ned
by their respective receptors for antigens, the B cell receptor (BCR) and the T cell receptor (TCR),
respectively.
Both BCRs and TCRs are integral membrane proteins, present in many identical copies, and
exposed at the cell surface. They are present before the cell encounters an antigen and characterized
by a unique binding site. A portion of the antigen called an epitope binds to the binding site, through
noncovalent interactions. Successful binding of the antigen receptor to the epitope (accompanied
by additional signals) will result in stimulation of the cell to enter the cell cycle. Repeated mitosis
leads to the development of a clone of cells bearing the same antigen receptor; thus, a clone of cells
of identical specii city. BCRs and TCRs are different with respect to their structure, the genes that
encode them and the type of epitope they bind.
