Targets of the immune system are infection, cancer and atherosclerosis.
a)Skin and mucosa.
The body is wrapped with skin which acts as a tough physical barrier against invasion of microorganisms. The digestive, respiratory and urinary tract, and reproductive organ are open to the outer environment through orifices. Their surface is covered with mucosal layer which acts a physical barrier against invasion of microorganisms.
Skin has its own specific skin immune system. Cells of mucosal system secrete substances which can destroy microorganisms and convey them toward outside of the body. At the same time, mucosal layer, has its own specific mucosal immune system. This is closely related with cells of systemic immune system composing peripheral blood and lymphoid tissues. These immune systems play major role in innate and acquired immunity, described below.
The innate immunity works together with acquired immunity described below. Cells of innate immunity are neutrophils (polymorph nuclear leukocytes: polymorphs), monocytes (macrophages are sometimes used as synonymously), dendritic cells and natural killer cells. These cells are circulating in the peripheral blood and residing in lymphoid tissues such as lymph nodes, tonsils, spleen and intestine.
Recognition of microorganisms by cells of innate immunity is mediated by toll-like receptors (TLR). TLR recognizes pathogen-associated molecular patterns that are persevered in pathogenic microorganisms such as bacteria, fungi, parasites and virus, but not in mammalian cells. Information of infective microorganisms recognized by monocytes and dendritic cells is conveyed to lymphocytes playing an important role in the acquired immune system. NK cells attack and destroy neoplastic cells and virus infected cells expressing low level of or no MHC class I molecule.
Lymphocytes are major component of acquired immunity. T cells and B cells are two major components of lymphocytes. T cells and B cells are composed of innumerable number of clones each of which recognizes a specific foreign antigen present in all substances within and outside the body. Just as the cells of innate immunity, they are circulating in the peripheral blood and residing in lymphoid tissues such as lymph nodes, tonsils, spleen and intestine.
At the time of birth, the acquired immunity does not work efficiently,
as every clone responding to a foreign antigen of microorganisms in the
outer environment is still very small in number. After exposure to many
foreign antigens of microorganisms, the clones increase in size and can
respond efficiently to them. In other words, the function of acquired immunity
quickly grows after the birth.
Once exposed to some organism, lymphocytes obtain memory and respond very quickly and remove the same organism at the time of repeated infection. This is called immunological memory.
The activity of acquired immunity peaks at around adolescence and gradually decline thereafter. But the grade of the decline is different by individual. The acquired immunity is also susceptible to stress, disease and inappropriate life style, and lose the activity.
The recovery of the immunological activity can occur, but magnitude of the recovery is different by individual and age. Therefore, the level of activity of acquired immunity is different by individuals.
Accordingly, it is important to assess the activity level of acquired immunity in order to manage healthy level and control diseased condition.
HLS developed the method to assess the activity level of immunity composed of T cells, B cells and NK cells using lymphocytes in the peripheral blood and express it as a whole as a numeral. We name it immunological vigor.
Infectious pathogenic microbes invading living body are first recognized and attacked by cells of innate immunity; Neutrophils, NK cells, Macrophages and Dendritic cells. Information of infection is transferred by dendritic cells to lymphocytes, cell of acquired immunity . Dendritic cells present antigen to T cells for differentiation of helper T cells and killer T cells. Helper T cells help proliferation of killer T cells , and also promote proliferation and differentiation of B cells for production antibody. Killer T cells destroy cells infected with virus and antibody directly disposes pathogenic microbes.
Cancer occurs as a result of genomic abnormality, mostly developed after birth and accelerated in incidence after mid-age. Because of genomic abnormality, abnormal proteins are expressed on the membrane of cancer cells and can be usually recognized by immune cells such as T cells, NK cells, LAK (Lymphokine activated K) cells, ADCC (antibody dependent cytotoxic cells) and macrophages.
Among T cells, CD8+ killer T cells fulfill a role against cancer cells. Again APC (antibody presenting cells) such as macrophages and dendritic cells comes on stage. APC recognizes disposes of degenerated cancer cells and express cancer antigen on the cell membrane. In this case, the digested cancer-specific peptide should be in groove of MHC class I. CD8+ killer T cells can recognize the cancer peptide in groove of MHC class I and be activated for killer T cells against cancer cells. It is important to note that a small population of CD8+ killer T cells corresponding to the presented cancer antigen should expand
the population by extensive proliferation and combat with cancer cells
that express MHC class I together with cancer antigen.
Because of genomic abnormality, many cancer cells do not express MHC class I.
In this case, NK cells acquire the cytotoxic role and attack cancer cells. NK cells express NKG2D which recognize MICA/MICB (MICA/B) molecule on cancer cells and shed killing signal. MICA/B molecule is usually expressed on cancer cells or virus-infected cells. When normal cells are exposed to stress and express MICA/B, they are not attacked by NK cells because of the presence of MHC class I, as an important ID marker of “self” suppresses cytotoxic function by NKG2D .
|Cancer cell injury by killer T cells and NK cells|
|Cancer cells with MHC class Ｉ （） are attacked by, CD8+ killer T cells through cancer antigen in the MHC class I groove. Cancer cells without MHC class I usually express MICA/MICB (MICA/B) molecule () which is recognized by NK cells or γδ type T cells through NKG2D ()receptors and attacked.|
|Cancer cells with MHC class I||Cancer cells with MICA/B|
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