THE ADAPTIVE IMMUNE SYSTEM

I. INTRODUCTION

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

8. INVARIENT NATURAL KILLER T-LYMPHOCYTES (iNKT CELLS)

Fundamental Statements for this Learning Object:

1. iNKT cells have T-cell receptors (TCRs) on their surface for glycolipid antigen recognition, as well natural killer (NK) cell receptors.
2. Through the cytokines they produce, iNKT cells are essential in both innate and adaptive immune protection against pathogens and tumors.
3. iNKT cells also play a regulatory role in terms of the development of autoimmune diseases, human asthma, and transplantation tolerance.
4. Through the rapid productions of such cytokines, iNKT cells are able to promote and suppress different innate and 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 iNKT cells.

Invariant Natural Killer T-lymphocytes (iNKT Cells) (def)

iNKT cells are a subset of lymphocytes that bridge the gap between innate and adaptive immunity. They have T-cell receptors (TCRs) (def) on their surface for glycolipid antigen recognition. They also have natural killer (NK) cell (def) receptors. NK cells are discussed later in this unit.

Through the cytokines (def) they produce once activated, iNKT cells are essential in both innate and adaptive immune protection against pathogens and tumors. They also play a regulatory role in the development of autoimmune diseases, asthma, and transplantation tolerance. It has been shown that iNKT cell deficiency or disfunction can lead to the development of autoimmune diseases, human asthma, and cancers.

Pathogens may not directly activate iNKT cells. The TCR of iNKT cells recognize exogenous glycolipid antigens (def), as well as endogenous self glycolipid antigens (def) presented by MHC-I-like CD1d molecules on antigen presenting dendritic cells (def).

Antigen-presenting dendritic cells engulf glycolipids from certain microorganisms (exogenous glycolipids) and degrade them with their lysosomes (see Fig. 1). Dendritic cells also engulf certain glycolipids from human cells (endogenous glycolipids) and degrade them with their lysosomes (see Fig. 2). These glycolipid epitopes are then bound to CD1d molecules produced by dendritic cells and transported to the surface of the cell where they can be presented to the TCR of iNKT cells to induce iNKT cell activation (see Fig. 1 and Fig. 2). iNKT cells can also be activated by the cytokine Interleukin-12 (IL-12) produced by dendritic cells that have themselves become activated by pathogen-associated molecular patterns (PAMPs) (def) of microbes binding to the pattern-recognition receptors (PRRs) (def) of the dendritic cell (see Fig. 3).

Once activated, the iNKT cells rapidly produce large quantities of both T_H1 cell and T_H2 cell cytokines, including interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interleukin-13 (IL-13), and chemokines. Through the rapid productions of such cytokines, iNKT cells are able to promote and suppress different innate and adaptive immune responses. For example, large amounts of IFN-γ are produced by activated iNKT cells. IFN-γ activates NK cells and macrophages (def) as a part of innate immunity; it also promotes the maturation of dendritic cells so that they induce a T_H1 cell response to induce adaptive immunity.

It has been proposed that if the iNKT cell is repeatedly stimulated by the body's own glycolipids in the ab sense of microbes that this might stimulate the iNKT cell /dendritic cell interaction to produce tolerizing signals that inhibit the T_H1 cell response and possibly stimulate the production of regulatory T-lymphocytes (T_reg cells). In this way it might suppress autoimmune responses and prevent tissue damage.

There is also growing evidence that early childhood exposure to microbes is associated with protection against allergic diseases, asthma, and inflammatory diseases such as ulcerative colitis. It has been found that germ-free mice have large accumulations of mucosal iNKT cells in the lungs and intestines and increased morbidity from allergic asthma and inflammatory bowel disease. However, colonization of neonatal germ-free mice with normal microbiota resulted in mucosal iNKT cell tolerance to these diseases. It has been proposed that microbes the human body has been traditionally exposed to from early childhood throughout most of human history might play a role in developing normal iNKT cell numbers and iNKT cell responses.

 

Concept Map for T-lymphocytes

 

 

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