THE ADAPTIVE IMMUNE SYSTEM

I. INTRODUCTION

B. MAJOR CELLS AND KEY CELL-SURFACE MOLECULES INVOLVED IN ADAPTIVE IMMUNE RESPONSES

4. T4 -Lymphocytes (T4-Cells; T4-Helper Cells; CD4⁺ Cells)

The overall purpose of this Learning Object is:
1) to learn how T4-lymphocytes are activated during adaptive immune responses; and
2) to learn the functions of T4-lymphocytes in adaptive immune responses.

LEARNING OBJECTIVES FOR THIS SECTION

Adaptive (acquired) immunity refers to antigen-specific defense mechanisms that take several days to become protective and are designed to remove a specific antigen (def). This is the immunity one develops throughout life. There are two major branches of the adaptive immune responses: humoral immunity and cell-mediated immunity.

1. humoral immunity (def): humoral immunity involves the production of antibody molecules in response to an antigen (def) and is mediated by B-lymphocytes.

2. cell-mediated immunity (def): Cell-mediated immunity involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen (def) and is mediated by T-lymphocytes.

We will now take a look at T4-lymphocytes.

T4-Lymphocytes (T4-Helper Cells, CD4⁺ Cells) (def)

T-lymphocytes refer to lymphocytes that are produced in the bone marrow but require interaction with the thymus for their maturation. T4-lymphocytes are T-lymphocytes displaying a surface molecule called CD4 (def). They also have on their surface, epitope receptors called T-cell receptors (def) or TCRs that, in cooperation with the CD4 molecules (def), have a shape capable of recognizing peptides from exogenous antigens (def) bound to MHC-II (def) molecules on the surface of antigen-presenting cells (def) (APCs) such as dendritic cells, macrophages, and B-lymphocytes (see Fig. 1 and Fig. 2). The TCR recognizes the peptide while the CD4 molecule recognizes the MHC-II molecule.

During its development, each T4-lymphocyte becomes genetically programmed by gene-splicing reactions similar to those in B-lymphocytes, to produce a T-cell receptor or TCR (def) with a unique specificity. Identical molecules of that TCR are placed on its surface where they are able to bind an epitope/MHC-II complex on an APC (def) such as a dendritic cell, a macrophage, or a B-lymphocyte (def) with a corresponding shape. It is estimated that the human body has the ability to recognize 10⁷ or more different epitopes (def). In order to recognize this immense number of different epitopes, the body produces 10⁷ or more distinct clones of T-lymphocytes, each with a unique T-cell receptor. In this variety of T-cell receptors there is bound to be at least one that has an epitope-binding site able to fit, at least to some degree, peptides of any antigen the immune system eventually encounters.

Effector T4-lymphocytes (def) are cells the body uses to regulate both humoral immunity and cell-mediated immunity through cytokine they produce. In order to do so, however, naive T4-lymphocytes (def) must first become activated by cytokines (def) produced by APCs as shown in Fig. 3 and Fig. 4.

Flash animation of MHC-II molecules binding epitopes from exogenous antigens.

Flash animation of a naive T4-lymphocyte recognizing epitopes bound to MHC-II molecules on an antigen-presenting dendritic cell and the subsequent activation of that naive T4-lymphocyte by the dendritic cell.

 

• To view an electron micrograph of a dendritic cell presenting antigen to T-lymphocytes, #1 see the Web page for the University of Illinois College of Medicine.
• To view an electron micrograph of a dendritic cell presenting antigen to T-lymphocytes, #2 see the Web page for the University of Illinois College of Medicine.
• Scanning electron micrograph of a dendritic cell interacting with a T-lymphocyte from sciencephotogallery.com.

The various molecular interactions between the APC and the T4-lymphocyte produce signals and cytokines for the activation of the naive T4-lymphocyte. The signals and cytokines from the APC activate transcription factors in the T4-lymphocyte that bind to and activate genes responsible for the proliferation of that T4-lymphocyte and its differentiation into an effector cell (def). Functionally, there are many different types or subpopulations of effector T4-lymphocytes based on the cytokines they produce. Chronic immune reactions are typically dominated by three primary types:

• T_h1 cells:

Produce cytokines that promote cell-mediated immunity (def) - especially
against intracellular microbes by activating macrophages and cytotoxic T-lymphocytes, promote the production of antibodies that promote phagocytosis, and block the production of T_h2 cells;

• T_h2 cells:

  Produce cytokines that promote responses against helminths (def) and allergens (def), promote the production of antibodies that neutralize microbes and toxins, promote the removal of microbes in mucosal tissues, and block the production of T_h1 cells; and

• T_h17 cells:

  Induce inflammatory reactions rich in neutrophils.

The overall role of these effector T4-lymphocytes is to:

1. activate macrophages (def) and NK cells (def) - see Fig. 5 .

Flash animation of the activation of a macrophage by a Th1 cell.

2. produce cytokines that enable activated B-lymphocytes to rapidly proliferate, differentiate into effector cells, and produce different classes or isotype (def) of antibodies (see Fig. 10). This is essential in order to produce enough specific B-lymphocytes and sufficient quantities of antibodies to mount an effective immune response.

3. produce cytokines (def) that enable activated T-lymphocytes to rapidly proliferate and differentiate into effector cells (def). This is essential in order to produce enough specific effector T4-lymphocytes and effector T8-lymphocytes to mount an effective immune response. Effector T4-lymphocytes regulate the immune responses through cytokine production and effector T8-lymphocytes function as cytotoxic T-lymphocytes (def) or CTLs used by the body to remove infected cells and tumor cells.