T-lymphocytes memory

The ideal of any vaccine is to provide life-long protection to the individual against disease. Immunological memory (Chapter 14) depends upon the survival of cloned populations of small B and T lymphocytes (memory cells). These small lymphocytes have a lifespan in the body of ca. 15-20 years. Thus, if the immune system is not boosted, either by natural exposure to the organism or by re-immunization, then immunity gained in childhood will be attenuated or lost completely by the age of 30. Those vaccines which provide only poor protection against disease have proportionately reduced time-spans of effectiveness. Yellow fever vaccination, which is highly effective, must therefore be repeated at 10-year intervals, whilst typhoid vaccines are only effective for 1-3 years. Whether or not immunization in childhood is boosted at adolescence or in adult life depends on the relative risks associated with the infection as a function of age. 

In contrast to naive T lymphocytes, memory T lymphocytes migrate non-randomly in a partially tissue-specific fashion (Salmi et til., 1992), suggesting that the mucosal environment in which T lymphocyte activation occurs may imprint a pattern of selectivity on the activated cell. The selective migration of a subset of T lymphocytes through the gut is probably the best characterized example of tissue-specific homing (Mackay,... 

Selin L K, Vergilis K, Welsh R M, et al. (1996). Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections. /. Exp. Med. 183 2489-2499. 

Stable Virus-Specific Cytotoxic T Lymphocyte Memory by Heterologous Viral Infections. r Fxo Med 183 2489-2499 (1996). 

Part of these T-lymphocytes transform into memory cells. These cells are different from their ancestors in that they are activated by a much lower antigen binding strength and also much less depend on signal 2. Now self-antigens can activate these T-lymphocytes. As during activation continuously new memory cells are formed, autoreactivity is sustained and autoimmune disease follows (Fig. 2). 

Memory T lymphocytes—recognize previous contact with antigens and activate an immune response... 

Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999 401 708-712. 

In an immune response, antibodies are produced and secreted by the B-lymphocytes in conjunction with the T, cells. In the majority of hapten-carrier systems, the B cells end up producing antibodies that are specific for both the hapten and the carrier. In these cases, the T lymphocytes will have specific-binding domains on the carrier, but will not recognize the hapten alone. In a kind of synergism, the B- and T-cells cooperate to induce a hapten-specific antibody response. After such an immune response has taken place, if the host is subsequently challenged with only the hapten, usually it will respond by producing hapten-specific antibodies from memory cells formed after the initial immunization. For a review of immunobiology (see Janeway, 2004). 

Sanders, M.E.. et al., Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, andLFA-1) and three other molecules(UCHLl, CDw29, Pgp-1) and have enhanced IFN-gamma production, J. Immunol, 140, 1401, 1988. 

CpG ODNs are also effective as vaccine adjuvants to enhance adaptive TH1 cellular immune responses.104 In mice, CpG ODNs can trigger strong TH1 responses,105 enhancing the number and function of tumor-specific Cytotoxic T lymphocytes (CTLs) and IFN-y secreting T cells.106 This has resulted in therapeutic vaccines in mouse tumor models where no other approach has shown comparable efficacy, even with large (1 cm) established tumors.107 108 Even without a vaccine, CpG ODNs can induce CD8+ T cell-mediated regression of established tumors with durable memory responses.109... 

The effects of Pb on the mixed lymphocyte response (MLR) have been examined in prior studies. McCabe and colleagues [53] and Farrer and colleagues [54] demonstrated that Pb in vitro at very low concentrations (0.1 pM = 2 pg/dL) significantly enhanced the proliferation and expansion of murine alloreactive CD4+ T lymphocytes in the MLR. The expanded T cell population was found to have a high density of CD4 molecules on the cell surface making them phenotypically similar to memory/effector T lymphocytes. In a study using Lewis strain rats, Razani-Boroujerdi and coworkers [55] also found evidence for Pb-induced stimulation of the in vitro MLR. 

Wonnacott, K.M. and Bonneau, R.H., The effects of stress on memory cytotoxic T lymphocyte-mediated protection against herpes simplex virus infection at mucosal sites, Brain Behav. Immun., 16, 104, 2002. 

On the one hand, are the soluble factors such as lysozyme and complement, together with the phagocytic cells that contribute to the innate system, and on the other hand are the lymphocyte-based mechanisms that produce antibody and the T lymphocytes, which represent the main elements of the adaptive immune system. Not only do these lymphocytes provide improved resistance by repeated contact with a given infectious agent, but the memory with which they become endowed shows very considerable specificity to that infection. 

Lombardi, V.R.M., Amado, L., Femandez-Novoa, L., Ftcheverrfa, 1., Seoane, S., Cacabelos, R. (2003) Flow cytometry analysis of CD28-/CD8-I- suppresor cell precursor and CD45RO-I-/ CD4-I- memory T lymphocytes in the peripheral blood of Alzheimer s disease patients. In New trends in Alzheimer- and Parkinson-related disorders, Hanin, 1., Fisher, A., Cacabelos, R. (eds.), Monduzzi Fditore, Bologna, pp. 57-61. 

In addition, a distinction is made between cellular and humoral immune responses. The T lymphocytes (T cells) are responsible for cellular immunity. They are named after the thymus, in which the decisive steps in their differentiation take place. Depending on their function, another distinction is made between cytotoxic T cells (green) and helper T cells (blue). Humoral immunity is based on the activity of the B lymphocytes (B cells, light brown), which mature in the bone marrow. After activation by T cells, B cells are able to release soluble forms of their specific antigen receptors, known as antibodies (see p. 300), into the blood plasma. The immune system s memory is represented by memory cells. These are particularly long-lived cells that can arise from any of the lymphocyte types described. 

Activated and memory T lymphocytes in human milk. Cytometry 13, 282-290. 

After tissue transplantation, the severity and the period of rejection depend on the tissue type, and this process involves the specificity and memory components of the immune response. Avrion Mitchison in the 1950s observed that allograft immunity could be transferred by the components of the cellular immune response, and antibodies present in the serum that were part of the humoral response were not associated with this process. Future studies delineated the role of T lymphocytes in the allograft rejection process, and the role of both CD4+ and CD8+ cells was established. 

Schall, T. J., Bacon, K., Toy, K. J., and Goeddel, D. V. (1990). Selective attraction of monoctyes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347, 669-671. Senkevich, T. G., Bugert, J. J., Sisler, J. R., Koonin, E. V., Darai, G., and Moss, B. (1996). Genome sequence of a human tumorigenic poxvirus Prediction of specific host response-evasion genes. Science 273, 813-816. 

---