The Adaptive Immune System
From MyMCAT
Contents |
Introduction
While the innate immune system provides a immediate response to infection, it is often overrun or evaded allowing the infection to potentially become more serious. It is here that the adaptive immune system begins to specifically target these more serious infections and prevent them from severely hurting us.
This system is subdivided into two unique subsystems which both act by being presented with novel pathogen targets and developing appropriate methods to attack them along with a system for remembering these pathogens for future attacks if necessary.
(For a full list of materials on the immune system, please visit Category:The Immune System.)
The T-Cell Response
T-cell Maturation
Mature T-cells are found throughout the circulatory and lymphatic system and are essentially cells which have been selected to recognize foreign peptides presented on cells throughout the body. The process by which these cells are made is called T-cell maturation. Their progenitors, which began in the bone-marrow, migrate to the thymus gland early in life where they then undergo a unique proliferation and selection system.
Sequestered in the thymus, T-cells begin expressing their T-cell receptor (TCR) and interact with the surround gland tissues. These receptors uniquely evolve through a controlled mutation process such that every T-cell receptor becomes capable of binding unique peptide-MHC complexes on cell surfaces. By the end of the selection process (which involves both positive and negative selection), the T cells that remain are capable of binding unique MHC-peptide targets without binding accidentally binding natural host targets. Those that fail the selection process are rapidly induced to die and failure in this process can often lead to autoimmune diseases (in which the T-cells accidentally attack normal host cells).
Once the process is complete, the mature T-cells are free to circulate in the blood and lymphatic systems where they are continuously exposed to MHC complexes of all the cells they pass by. In a healthy individual, T-cells may potentially bind MHC complexes, but because the epitopes presented will be host factors and not match what the T-cells are trained for, no immune response will occur.
Host Presentation of Pathogenic Peptides
Nearly all cells in the body express the MHC complex on their surface and thus all of these cells are capable of triggering T-cell responses. There are two methods by which these cells present peptides in their MHC-complexes. The first is performed whenever phagocytic cells engulf various virus, bacterial, fungal, or protein particles; digest them; and then display them on their own surface in the MHC complex. Thus, through this mode of action, engulfed pathogen fragments or peptides can be displayed.
The second mode of MHC presentation is performed by cells all the time. Throughout daily protein synthesis activities of cells, a small number of proteins and peptides are redirected away from their target purpose, and instead sent to the golgi for redirection to the cell surface for presentation in the cell's MHC complexes. Through this process, if a virus or bacteria infiltrates a human cell and begins replicating, some peptides from the pathogen will also get presented and so become targets for the immune system.
Activation of the T-cell Response
The T-cells, which have been trained in the thymus to know what are host and nonhost (i.e. pathogen associated) peptides will immediately respond to any cells that are expressing nonhost peptides. In response to this activation signal, those specific T-cells proliferate and neutralize any cells which express the MHC complex containing their target peptide. When an infection has subsided and the infected cells are destroyed, the T-cells will receive less activation signal and return back to a dormant state to once again await their activation signal when needed.
The B-Cell Response
B-cell Maturation
Like the T-cells, B-cells originate from the bone marrow, however unlike the T-cells which must mature in the thymus, B-cells remain in the bone marrow until they are fully matured.
During the process of B-cell maturation, the B-cell receptor undergoes a series of mutation and selection processes just as the T-cells do. This receptor will eventually become the principle component of what will be free circulating antibodies, but during this initial process they are confined to remain on the cell surface. Receptors are rapidly evolved to bind a huge variety of structures, and unlike those of T-cells, which are limited to mostly peptides inside an MHC complex, the B-cell receptor can bind anything that it evolves affinity for (whether it be sugars, bacterial cell wall components, viral coat proteins, toxins, unnatural chemicals, etc).
These B-cells, once matured also circulate in the lymphatic vessels but remain inactive unless their receptor comes in high affinity contact with a target molecule.
Activation of the B-cell Response
When a B-cell binds a target with high affinity, and if other appropriate signals are present, the B-cell will become activated. This activation leads to the same proliferation events that occur in T-cells however it also begins a process known as antibody isotype switching and evolution. During the proliferation process, some B-cell receptors will be modified such that they are no longer membrane bound (IgM type) but rather become soluble (IgA, IgG, IgE, etc). Thus these differentiated B-cells rapidly secrete excess amounts of the soluble antibodies into the blood stream allowing them to bind pathogens throughout the area of infection. The antibodies when bound to a target can either directly block them from functioning (an antibody bound to the fusion protein of a virus for instance can prevent the virus from entering cells) or it may allow other lymphatic cells to recognize and destroy the target (NK cells, Mast cells, Eosinophils etc).
During the proliferation phase, B-cells are often also able to alter their receptors and thus produce slight changes in the antibody they produce leading to the development antibodies with stronger affinity for the target (this also helps when the pathogen mutates to resist being a target by an antibody).
Once an infection has been cleared, the B-cells return to a dormant state but some persist as memory B-cells which will produce a low level amount of the specific antibody for years.
Adaptive Immunity and Immunological Memory
Because of the persistence of T-cells and B-cells after an infection has cleared, subsequent reinfection to a previously seen pathogen allows the body to quickly reinitiate the same attack on the invader. It is this process that makes one "immune" to a pathogen they have previously been exposed to. (only in vary rare cases can you get chicken pox a second time!)
It is with the knowledge of these systems that scientists have been able to develop vaccines. By intentionally exposing an individual inactivated pathogens, proteins from pathogens, or even unique sugar complexes found on pathogens, once can trick the individual's immune system into mounting an immune response against the "invader" such that when the real pathogen enters the body, the immune system is already prepared for it. An ideal vaccine utilizes pathogen components which stimulate both T-cells and B-cells for the best results however, even under ideal circumstances, immunity may not be 100% and thus booster shots may be necessary to maintain the protective immunity.
