negative selection

Examples of negative selection in the following topics:

• Maturation of T Cells

  • T cells originate from hematopoietic stem cells in the bone marrow and undergo positive and negative selection in the thymus to mature.
  • The earliest thymocytes express neither CD4 nor CD8, and are therefore classed as double-negative (CD4-CD8-) cells.
  • The potentially autoimmune cells are removed by the process of negative selection.
  • Negative selection removes thymocytes that are capable of strongly binding with self-antigens presented by MHC.
  • These autoimmune disorders may be caused by problems in negative selection and tend to have genetic components.

• Lymphocytes

  • They have an immunosuppressive effect that inhibits cell-mediated immunity at the end of a response and destroys autoimmune T cells that aren't filtered out by negative selection in the thymus.
  • While in the bone marrow, B cells are sorted through positive and negative selection in a manner somewhat similiar to T cell maturation in the thymus, with the same process of killing B cells that are nonreactive to antigens or reactive to self-antigens.

• Clonal Selection and T-Cell Differentiation

  • Antigens are "selected" to form clones of themselves, both memory and effector.
  • Clonal selection is an theory that attempts to explain why lymphocytes are able to respond to so many different types of antigens.
  • Clonal selection assumes that lymphocytes already have receptors for that antigen, and are selected during antigen presentation because they already have that unique antigen receptor.
  • Clonal selection means that an antigen is presented to many circulating naive B and (via MHC) T cells, and that the lymphocytes that match the antigen are "selected" to form clones of themselves, both memory and effector.
  • Clonal selection may also be used during negative selection during T cell maturation.

• Clonal Selection and B-Cell Differentiation

  • B Cells develop in way that is similar but different to T cells, and undergo clonal selection
  • This is a form of positive selection.
  • They are also tested for autoreactivity through negative selection.
  • Clonal selection is theory in which it is postulated that a B cell expresses antigen specific receptors before antibodies even encounter an antigen or before that antigen is ever found in the body.
  • Following the initial infection, random mutations during clonal selection could have produced memory B cells that can more easily bind to antigens than the original B cells could.

• Specific T-Cell Roles

  • Differentiation into helper T cell subtypes occurs during clonal selection following T cell activation of naive T cells.
  • Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.

• Antimicrobial Proteins

  • These peptides have a stronger positive than negative charge, which is an important component of their selectivity.
  • The initial contact between the peptide and target organism is electrostatic due to the force of negative and positive ionic charge.
  • The peptides are selective and thus more likely to adhere to bacterial cell membranes than to cell membranes of the host cells.
  • The peptides have a greater positive charge than negative charge, while bacterial cell membranes have a greater negative charge than host cell membranes.
  • Bacteria like staphylococcus aureas, which forms the highly resistant MRSA strain, can reduce the negativity of the charge of its cell membrane by bringing amino acids from the cytoplasm into its cell membrane so antimicrobial peptides won't bind to it.

• Stress and Disease

  • In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated by a down-regulation of its negative feedback controls.
  • The negative feedback of cortisol to the hypothalamus, pituitary, and immune systems is impaired.
  • An increase in noradrenaline in the frontal/prefrontal cortex modulates the action of selective noradrenaline re-uptake inhibition and improves mood.
  • Excessive cortisol release also has a negative impact on heart health.

• Erythroblastosis Fetalis (Hemolytic Disease of the Newborn)

  • In terms of natural selection, she was selected against.
  • Rhesus-negative mothers who have had a pregnancy with/are pregnant with a rhesus-positive infant are given Rh immune globulin (RhIG) at 28 weeks and 34 weeks during pregnancy, and within 72 hours after delivery to prevent sensitization to the D antigen.

• Posttraumatic Stress Disorder (PTSD)

  • PTSD is believed to be caused by experiencing any of a wide range of events which produces intense negative feelings of "fear, helplessness, or horror" in the observer or participant.
  • Cognitive behavioral therapy (CBT) seeks to change the way a trauma victim feels and acts by changing the patterns of thinking or behavior, or both, responsible for negative emotions.
  • SSRIs (selective serotonin reuptake inhibitors) are considered to be a first-line drug treatment.

• Thyroid Gland Disorders

  • The disease can result in the formation of a toxic goiter as a result of thyroid growth in response to a lack of negative feedback mechanisms.
  • Radioactive iodine is administered in order to destroy a proportion of or the entire thyroid gland, since the radioactive iodine is selectively taken up by the gland and gradually destroys the cells of the gland.
  • Negative feedback mechanisms result in growth of the thyroid gland when thyroid hormones are being produced in sufficiently low quantities as a means of increasing the thyroid output.