| Themes > Science > Life Sciences > General Biology > Immunology > The Immune System & Its Effector Mechanisms > The Human Immune System & The Immune Response > Regulation of the Immune Response |
Regulation of the immune response (i.e. regulation and differential responses) based on the following factors
Prior exposure to ag Q What is the overall result of primary exposure to antigen? A Primary exposure to ag can lead to 2) induction of tolerance Q We’ve mentioned tolerance in light of transplantation. But mechanisms for inducing tolerance couldn’t have evolved in anticipation of medical technology. So, what is the evolutionary advantage to tolerance? A Tolerance (induction of anergy)
may simply be a reflection of the mechanisms for negative selection
against self-reacting B and T cells. Tolerance may be necessary so the
immune system doesn’t respond to "self"-antigens to which it
is not exposed during maturation. Q When does the body naturally contain tissues which are genetically disimilar (besides the rearranged B and T cells leading to idiotopes on ab and TCR — see later). A During sperm and egg cell production and pregnancy.
e.g. A mouse will develop a given response when infected with horse red blood cells (HRBC). However, if it is first primed a few days before by an injection of sheep RBC, the later response to HRBC is less than if the SRBC had not been injected. Thus, prior exposure to an unrelated antigen and priming of an ab response, reduced the subsequent ab response. A This may result from interference by the first ag utilizing much of the APC capacity so the second ag is not as effectively presented and/or by the presence of down-regulating cytokines in the process of reducing the response to the first ag. Circulating ab Circulating ab may invoke a sort of negative feedback mechanism. For example, circulating maternal ab interferes with childhood vaccinations in kids under a year -- the MMR vaccine for measles, mumps and rubella is not given until 1 year since it is not likely to elicit an immune response prior to that. Q Why? A One way this might occur is by the circulating ab binding to the ag and promoting clearance before any naive B cells can bind and become activated. Consider the following. A primary immune response to a carrier + hapten A generates circulating ab to hapten A. Next, a carrier with hapten A and a second hapten B is introduced to elicit a secondary response to hapten A. If the earlier statement is true, you would expect the circulating ab to bind to the hapten A epitopes and assist clearance of the whole carrier + hapten A + hapten B complex before an immune response to the hapten B could be elicited. However, it turns out that this doesn’t happen and a response to the second hapten does develop. Therefore, it is likely that circulating ab inhibits immune response in an epitope-specific fashion by competing for ag with the ab on naive B cells. If the circ. ab. binds all the epitopes, then the naive B cells, which are in low concentration, may never see the ag. However, other exposed epitopes such as those of hapten B in the example could be responded to. Cytokine-mediated regulation Two classes of T helper cells have been identified that secrete different sets of lymphokines and lead to different responses. TH1 cells secrete interferon gamma and IL-2, thus stimulating cytotoxic cells. These cells are also involved in delayed type (Type IV) hypersensitivity TH 2 cells secrete IL-4 and IL-5 which activate B cells, and IL-10 which suppresses TH1 cells. Anti-idiotypic ab: Network Theory As a humoral immune response arises and antibodies are made, the antibodies tend to become better at binding antigen. This is because, as ag is bound and cleared, a lower conc. remains and those B cells making ab with highest affinity to the ag are selected for. These ab are a result of new rearrangements of H and L genes (i.e. newly matured B cells) as well as somatic hypermutation of B cells which had been producing ab all along during this response. We know of this as affinity maturation. But what tones down the activity of plasma B cells? Since continued presence of ag isn’t necessary for ab production by existing plasma cells, you might expect them to produce copious amounts of antibody for a long time. In the mid 70’s Neils Jerne realized that the idiotypes of ab should be considered non-self since they arise late in dev. and throughout life and mutate frequently. In fact, if they were all considered self, one could never find anything that was non-self because of the tremendous diversity of idiotopes. So he proposed the network theory of immune regulation whereby, there is gigantic, complex network of antibodies and anti-antibodies and anti-anti-antibodies that keep each other in check. If one antibody is able to elicit production of another and so on, one might expect there to be almost constant stimulation so that great amounts of antibody are being produced at all times. However, studies reveal that antibody production actually rests at a steady state most of the time. Thus, Jerne proposed that each specific ab that is circulating is at low enough conc. so that it doesn’t stimulate a response. Only when the system is perturbed by presence of antigen is there an increase in any one type of ab. So when a large amount of ag is present, the B cells capable of making ab to that ag are activated. As the ab levels rise, anti-idiotypic ab levels follow and begin killing off excess plasma cells. Finally, when no ag is left, the steady state resumes. T Suppressor cells? Suppressor cells are T cells which have an ag-specific ability to suppress other T cells. They have all the markers of TC cells and it is widely debated whether they can be considered a separate subclass of T cells, yet they do seem to exist. They can suppress immunity in an ag-specific fashion when passively transferred. Neuroendocrine control There is increasing evidence that endocrine, nervous and immune systems interact via chemical mediators. |
|
|