The Innate Immune System: Nutritional Immunity

I. THE INNATE IMMUNE SYSTEM

I. NUTRITIONAL IMMUNITY

The overall purpose of this Learning Object is to learn how the ability to compete for key nutrients such as iron functions in innate immune defenses.

LEARNING OBJECTIVES FOR THIS SECTION

Innate immunity refers to antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to an antigen (def). This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

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 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 act as PAMPS. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)

Most body defense cells have pattern-recognition receptors for these common PAMPSand so there is 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.

The innate immune responses do not improve with repeated exposure to a given infection and involve the following:

phagocytic cells (neutrophils, monocytes, and macrophages);
cells that release inflammatory mediators (basophils, mast cells, and eosinophils);
natural killer cells (NK cells); and
molecules such as complement proteins, acute phase proteins, and cytokines.

Examples of innate immunity include anatomical barriers, mechanical removal, bacterial antagonism, pattern-recognition receptors, antigen-nonspecific defense chemicals, the complement pathways, phagocytosis, inflammation, and fever.

We will now take a closer look at nutritional immunity.

I. Nutritional Immunity

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 2, 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.

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