Self from Nonself

With aU the power the immune system has to attack foreign invaders, it must also do so with discretion, because we have our own cells that display proteins and other macromolecules on their surfaces. How the immune system knows not to attack these cells is a complicated and fascinating topic. When the body makes a mistake and attacks one of its own cells, the result is an autoimmune disease, examples of which are rheumatoid arthritis, lupus, and some forms of diabetes. 

Some mouse lymphocytes from spleen (red) make antibody to X 

Mutant mouse myeloma cells unable to grow in selective medium 

All of these safeguards lead to the delicate balance that must be maintained by the immune system, a system that simultaneously has the diversity to bind to almost any molecule in the Universe but does not react to the myriad proteins that are recognized as self. 

Researchers studying a herpes virus called human cytomegalovirus (HCMV) recently showed that one of the functions of the longer ncRNA from the virus was to allow the infected cells to evade the innate immunity response, as shown in the figure. RNAs make excellent weapons against the immune system. They are fast-acting because they do not need to be translated, and 

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The specific, or adaptive, immune system is characterized by memory, specificity, and the ability to distinguish self from nonself. The important cells of the adaptive immune system are the lymphocytes and antigen-presenting cells that are... 

This provides potential defensive proteins directed at almost every imaginable invader. It also ensures that every individual has a set of proteins that labels its own cells as "self," and that virtually every individual on earth has cell surface proteins different from those of every other person. In both the innate and adaptive responses the immune system must carefully distinguish "self" from "nonself."36 37 In the innate system this discrimination developed during evolution of the host and its pathogens. In the adaptive system it depends upon interaction of the T cells with surface molecules, primarily those of the major histocompatibility complex (MHC). 

T cells derive their name from the location of their production — the thymus, a small organ situated just above the heart. Examination of the developmental pathways leading to the production of mature cytotoxic and helper T cells reveals the selection mechanisms that are crucial for distinguishing self from nonself These selection criteria are quite stringent approximately 98% of the thymocytes, the precursors of T cells, die before the completion of the maturation process. 

The immune system is a complex network of checks and balances designed to discriminate self from nonself (foreign) tissues. It helps rid the body of infectious agents, tumor cells, and products associated with the breakdown of cells. In rheumatoid arthritis this system no longer can differentiate self from nonself tissues and attacks the synovial tissue and other connective tissues. 

It can recognize "self" from "nonself." When we are born, our immune system is already aware of aU the antigens of our bodies. These it recognizes as "self" and will not attack. Every antigen that is not classified as "self" will be attacked by the immtme system when it is encotmtered. Some individuals suffer from a defect of the immune response that allows it to attack the cells of one s own body. The result is an autoimmune reaction that can be fatal. 

Immune cells must also be able to recognize self from nonself. T cells and B cells are conditioned, in their early stages of development, not to recognize proteins from that individual. 

The specific, or adaptive, immune system is characterized by memory, specificity, and the ability to distinguish self from nonself. The important cells of the adaptive immune system are the lymphocytes and antigen-presenting cells that are part of nonspecific immunity. The lymphocytes, which originate from pluripotent stem cells located in the hematopoietic tissues of the liver (fetal) and bone marrow, are composed of two general cell types T and B cells. The T cells differentiate in the thymus and are... 

In nature, some assemblies form preferentially in the presence of mixmres of many other competitors. Consider, for example, a simple mixture with two assembly units (A and B). Each of these units has some preference to self-assemble and form homodimers (AA and BB) (Figure 10). They may also have some propensity to form heterodimers (AB) in a mixture. From a thermodynamic standpoint, selective self-assembly to afford exclusively homodimers is governed by the three equilibrium constants (Kaa, Kbb, and Kab). concentration, temperature, and the presence of competitors. This selectivity for a component is often referred to as self-sorting, which has been described by Lyle Isaacs as the high-fidelity recognition of self from nonself. ... 

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