I. THE INNATE IMMUNE SYSTEM

D. EARLY INDUCED INNATE IMMUNITY

8. NUTRITIONAL IMMUNITY

Fundamental Statements for this Learning Object:

1. Iron is needed as a cofactor for certain enzymes in both bacteria and humans.
2. Both bacteria and human cells produce iron chelators that trap free iron from their environment and transport it into the cell.
3. During infection, the body makes considerable metabolic adjustment in order to make iron unavailable to microorganisms.
4. The lack of iron can inhibit the growth of many bacteria.
5. Some bacteria in addition to their own siderophores, produce receptors for iron chelators of other bacteria and/or human cells and in this way take iron being trapped for use by other organisms.
6. A number of bacteria are able to produce toxins that kill host cells only when iron concentrations are low and in this way gain access to the iron that was in those cells.

 

LEARNING OBJECTIVES FOR THIS SECTION

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 nutritional immunity.

 

8. Nutritional Immunity

Iron is needed as a cofactor for certain enzymes in both bacteria and humans. Both bacteria and human cells produce iron chelators that trap free iron from their environment and transport it into the cell. During infection, the body makes considerable metabolic adjustment in order to make iron unavailable to microorganisms. Much of this is due to production of a defense chemical called leukocyte-endogenous mediator (LEM). As a result of infection, there is:

1. decreased intestinal absorption of iron from the diet;

2. a decrease of iron in the plasma and an increase in iron in storage as ferritin;

3. increased synthesis of the human iron-binding proteins (iron chelators) such as lactoferrin, transferrin, ferritin, and hemin that trap iron for use by human cells while making it unavailable to most microbes;

4. coupled with the febrile response, decreased ability of bacteria to synthesize their own iron chelators called siderophores;

5. prior stationing of lactoferrin at common sites of microbial invasion such as in the mucous of mucous membranes, and the entry of transferrin into the tissue during inflammation.

This lack of iron, which is needed as a cofactor for certain enzyme reactions, can inhibit the growth of many bacteria.

As seen in Unit 3, some bacteria produce in addition to their own siderophore, receptors for siderophores of other bacteria in this way take iron from other bacteria. Furthermore, a number of pathogenic bacteria are able to bind human transferrin, lactoferrin, ferritin, and hemin and use that as their iron source. For example, Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae are able to use iron bound to human transferrin and lactoferrin for their iron needs, while pathogenic Yersinia species are able to use transferrin and hemin as iron sources. Borrelia burgdorferi doesn't even use iron as a cofactor, but instead uses manganese. Furthermore, a number of bacteria are able to produce exotoxins that kill host cells only when iron concentrations are low. Perhaps in this way the bacteria can gain access to the iron that was in those cells.

 

• 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.