I. THE INNATE IMMUNE SYSTEM

D. EARLY INDUCED INNATE IMMUNITY

11. INTRAEPITHELIAL T-LYMPHOCYTES AND B-1 CELLS

Fundamental Statements for this Learning Object:

1. Most of the T-lymphocytes and B-lymphocytes in the body are involved in the adaptive immune responses wherein specific receptors on T-lymphocytes (T-cell receptors or TCRs) and B-lymphocytes (B-cell receptors or BCRs) recognize specific antigens of specific microbes.
2.  Intraepithelial T-lymphocytes and B-1 cells, however, are subpopulations of T-lymphocytes and B-lymphocytes that possess a more limited diversity of receptors and are designed to directly recognize the more common microbes that enter the epidermis or the mucosal epithelia and function more as effector cells for innate immunity rather than adaptive immunity.
3. Intraepithelial T-lymphocytes (IELs) are found in the epidermis of the skin and the mucosal epithelia.
4. It has been proposed that they recognize molecules such as MHC-I molecules and heat shock proteins associated with epithelial cells but expressed only when those cells are infected and trigger apoptosis of these stressed or infected cells. They may also aid in repair of mucous membranes following inflammatory damage.
4. B-1 lymphocytes, or B-1 cells, are found mostly in the peritoneal and pleural cavities.
5. B-1 cells have a limited diversity of antigen receptors that initially produce a class of antibody molecule called IgM against common polysaccharide and lipid antigens of microbes and against PAMPs.
6. Similar B-lymphocytes called marginal zone B cells are found in the spleen.\ and are thought to make IgM to protect against bacteria that enter the bloodstream.

 

LEARNING OBJECTIVES FOR THIS SECTION

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D. Early Induced Innate Immunity

Early induced innate immunity begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPs (def) binding to pattern-recognition receptors or PRRs (def). These recruited defense cells include:

• phagocytic cells: leukocytes such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells in the tissue such as macrophages (def);
  
• cells that release inflammatory mediators: inflammatory cells in the tissue such as macrophages and mast cells (def); leukocytes such as basophils and eosinophils; and
  
• natural killer cells (NK cells (def)).

Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells. These unique microbial molecules are called pathogen-associated molecular patterns or PAMPs (def) and include LPS from the Gram-negative cell wall, peptidoglycan and lipotechoic acids from the Gram-positive cell wall, the sugar mannose (a terminal sugar common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial and viral unmethylated CpG DNA, bacterial flagellin, the amino acid N-formylmethionine found in bacterial proteins, double-stranded and single-stranded RNA from viruses, and glucans from fungal cell walls. In addition, unique molecules displayed on stressed, injured, infected, or transformed human cells also be recognized as a part of innate immunity. These are often referred to as danger-associated molecular patterns or DAMPs.

Most body defense cells have pattern-recognition receptors or PRRs (def) for these common PAMPs (see Fig. 1) enabling an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 10³ of these microbial molecular patterns.

We will now take a closer look at Intraepithelial T-lymphocytes and B-1 cells.

11. Intraepithelial T-lymphocytes and B-1 cells

Most of the T-lymphocytes (def) and B-lymphocytes (def) in the body are involved in the adaptive immune responses that will be discussed in Unit 6. In adaptive immunity, specific receptors on T-lymphocytes (T-cell receptors or TCRs) and B-lymphocytes (B-cell receptors or BCRs) recognize specific antigens (def) of specific microbes.

For More Information: B-lymphocytes from Unit 6

For More Information: T4-lymphocytes from Unit 6

For More Information: T8-lymphocytes from Unit 6

Intraepithelial T-lymphocytes and B-1 cells, on the other hand, are subpopulations of T-lymphocytes and B-lymphocytes that possess a more limited diversity of receptors and are designed to directly recognize the more common microbes that enter the epidermis or the mucosal epithelia. As such, they function more as effector cells for innate immunity rather than adaptive immunity.

a. Intraepithelial T-lymphocytes (IELs) (def) are found in the epidermis of the skin and the mucosal epithelia. These T-lymphocytes, known as gamma:delta T-lymphocytes, differ from the T-lymphocytes (alpha:beta T-lymphocytes) associated with adaptive immunity. The alpha:beta T-lymphocytes are designed to recognize peptide antigens bound to MHC-I molecules of infected cells and tumor cells.

Although their exact function is unknown, it has been proposed that they recognize molecules associated with epithelial cells but expressed only when those cells are infected, such as MHC-I molecules and heat shock proteins. They then trigger apoptosis (def) of these stressed or infected cells using perforins and granzymes similar to cytotoxic T-lymphocytes (CTLs) (def) of adaptive immunity. Rather than recognizing antigens specific to an infectious microorganism, they recognize molecules associated with the epithelium as a consequence of infection. Their T-cell receptors may also function as PRRs for recognizing certain PAMPs. As such, they function more as effector cells for innate immunity rather than adaptive immunity. They probably help defend the body by producing cytokines (def) that play a variety of roles in body defense. IELs are also thought to aid in repair of mucous membranes following inflammatory damage. Excessive or inappropriate activation of IELs can also lead to damage of the intestines as in the case of celiac disease.

 

b. B-1 lymphocytes, or B-1 cells (def) are found mostly in the peritoneal (def) and pleural cavities (def). B-1 cells have a limited diversity of antigen receptors that initially produce a class of antibody molecule (def) called IgM against common polysaccharide and lipid antigens of microbes and against PAMPs. As such they function more as effector cells for innate immunity rather than adaptive immunity. Antibodies produced by B-1 cells are often called natural antibodies that help to protect against bacteria in body cavities. Similar B-lymphocytes called marginal zone B cells are found in the marginal zone of the white pulp of the spleen. These are thought to make IgM to protect against bacteria that enter the bloodstream.

• QUIZ YOURSELF ON THIS SECTION

Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.