Each T cell expresses a unique antigen -specific receptor molecule (TCR). TCRs, however, cannot directly recognize complete pathogenic structures. Instead the TCR recognizes molecular fragments (small peptides derived from processing of larger protein antigens) that have to be presented in association with major histocompatibility complex (MHC) molecules at the cell surface of antigen- presenting cells (APC). In consequence, activation of T-lymphocytes strongly depends on the interaction with APCs. Professional APCs, derived from specialized phagocytes termed dendritic cells (DCs), ingest pathogen -derived proteins. After phagocytosis the antigens are broken down and processed and the resulting peptide fragments are transported to the cell surface where they are embedded into MHC molecules. An individual T cell can only be activated by a peptide antigen for which it expresses the specific receptor. Moreover, besides its antigen specificity the TCR additionally can only interact with MHC molecules of its own tissue type. This quality is described as self-restriction and ensures that only cells of the same organisms will interact to mount an adaptive immune response .

T cells activated by antigen -bearing DCs express the CD4 cell surface protein and are restricted to recognize antigen in the context of MHC class II molecules. CD4+ T cells fulfill  modulatory and effector functions by secreting soluble factors (cytokines) that exert direct antimicrobial properties or affect the activities of other immune cells. In most cases CD4+ cells will help other immune cells to perform their task and are, therefore, referred to as helper T cells (Th). Based on the types of cytokines the Th cells secrete and their abilities to assist other subsets of immune cells, several sub populations of Th cells have been described. Th1 cells secrete mainly interferon-gamma (IFNγ), a cytokine known to limit pathogen survival. IFNγ also promotes the differentiation of cytotoxic lymphocytes (CD8+ cells see below) that are able to destroy cells infected by intracellular pathogens. T helper 2 cells produce various cytokines (interleukins [IL] IL-4, IL-5, IL-13) that preferentially activate innate immune cells (eosinophils, mast cells) especially facilitating the immune response to extracellular parasites (Fig. 1 ). Another subset, termed follicular T helper cell (Tfh) based on its tissue localization in follicular structures of lymph nodes, is characterized by the secretion of IL-21, a cytokine thought to favor the secretion of antibodies by antigen-specific B cells [ 1 ]. Finally regulatory T cells (Treg cells) belong to the CD4+ T cell subset. They inhibit immune or inflammatory responses by blocking the activity of effector T cells, helper T cells, and APCs. Treg are crucial to downregulate immune responses after an effective protective response, to maintain immunological self-tolerance process, and for the prevention of uncontrolled or chronic inflammatory responses.

Fig1. Specialized T-helper cells

T cells expressing the CD8 surface molecule represent T effector cells that have the capacity to eliminate cells infested with intracellular pathogens. Antigen recognition by CD8+ T cells depends on the fact that virtually all nucleated cells present fragments of intra cellular proteins at their Surface-MHC-molecules as part fragments of intracellular proteins present externally derived antigen fragments in association with MHC class II molecules, non-immune cells use MHC class I molecules to present peptides derived from intracellular sources. Thus, cells infected by intracellular pathogens will express antigenic fragments of the pathogen in addition to the normal set of self-antigens. CD8+ T cells continuously screen MHC class I molecules to detect non-self-antigens indicative for an intracellular infection. Cells displaying high levels of pathogen-derived peptides, e.g., in the case of a virus infection, subsequently will be killed by CD8+ T cells by secretion of cytotoxic factors. In addition, CD8+ T cells can inhibit viral replication without destroying the infected cells by producing cytokines that are able to interfere (interferon) with pathogen replication. CD8+ cytotoxic cells also can eliminate cells exhibiting abnormal host peptides, such as those presented by tumor cells, and therefore play an important role in the immune control of aberrant cell growth. Although CD8+ T cells can react directly to cells expressing non- self- antigen/MHC class I complexes, their optimal cytotoxic potential is achieved in the presence of cytokines produced by regulatory CD4+ T helper cells .

References

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[1] Vinuesa CG, Tangye SG, Moser B et al (2005) Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 5:853–865

مواضيع ذات صلة

Antigen - Antibody Interaction: Specificity and Cross - Reactivity

ANTIBODY SYNTHESIS

Tolerance to Commensal Microbes and Fetal Antigens

B Lymphocyte Tolerance

Peripheral T Lymphocyte Tolerance

Immune Memory

B Cells

إزالَةُ التَحسس نحو البنسلين Penicillin Desensitization

الحساسية نحو البنسلين

الفرق بين فَرْطُ التحسس والحساسية الدوائية

Immunologic Tolerance: General Principles and Significance

Functions of Antibodies at Special Anatomic Sites