I. THE INNATE IMMUNE SYSTEM
B. PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs), PATTERN-RECOGNITION RECEPTORS (PRRs), AND CYTOKINES IMPORTANT IN INNATE IMMUNITY
1. Pathogen-Associated Molecular Patterns (PAMPs)
The overall purpose of this Learning Object is:
1) to learn how the innate immune system is able to detect conserved microbial molecules (pathogen-associated molecular patterns or PAMPs) in order to detect microbial invasion and initiate innate immune defenses; and
2) to learn examples of microbial molecules that function as pathogen-associated molecular patterns (PAMPs).
LEARNING OBJECTIVES FOR THIS SECTION
Innate immunity is an antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. 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:
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 pathogen-associated molecular patterns (PAMPs).
1. Pathogen-Associated Molecular Patterns (PAMPs) (def)
In order to protect against infection, one of the first things the body must do is detect the presence of microorganisms. The body initially does this by recognizing molecules unique to groups of related microorganisms and are not associated with human cells. These unique microbial molecules are called pathogen-associated molecular patterns or PAMPs.
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 damage-associated molecular patterns or DAMP. (def) In all, the innate immune system is thought to recognize approximately 103 molecular patterns.
Examples of microbial-associated PAMPs include:
a. lipopolysaccharide (LPS) from the outer membrane of the gram-negative cell wall (see Fig. 2);
b. bacterial lipoproteins and lipopeptides (see Fig. 2);
c. porins in the outer membrane of the gram-negative cell wall (see Fig. 2);
d. peptidoglycan found abundantly in the gram-positive cell wall and to a lesser degree in the gram-negative cell wall (see Fig. 3);
e. lipoteichoic acids found in the gram-positive cell wall (see Fig. 3);
f. lipoarabinomannan found in acid-fast cell walls (see Fig. 4)
g. mannose-rich glycans (short carbohydrate chains with the sugar mannose or fructose as the terminal sugar). These are common in microbial glycoproteins and glycolipids but rare in those of humans (see Fig. 6).
h. flagellin found in bacterial flagella;
i. bacterial and viral nucleic acid. Bacterial and viral genomes contain a high frequency of unmethylated cytosine-guanine dinucleotide or CpG sequences (a cytosine lacking a methyl or CH3 group and located adjacent to a guanine). Mammalian DNA has a low frequency of CpG sequences and most are methylated which may mask recognition by pattern-recognition receptors (def). Also, human DNA and RNA does not normally enter cellular endosomes (def) where the pattern-recognition receptors for microbial DNA and RNA are located;
j. N-formylmethionine (def), an amino acid common to bacterial proteins;
k. double-stranded viral RNA unique to many viruses in some stage of their replication;
l. single-stranded viral RNA from many` viruses having an RNA genome;
m. lipoteichoic acids, glycolipids, and zymosan from yeast cell walls; and
n. phosphorylcholine and other lipids common to microbial membranes.
Examples of DAMPs associated with stressed, injured, infected, or transformed host cells and not found on normal cells include:
a. heat-shock proteins (def)
b. altered membrane phospholipids
To recognize PAMPs such as those listed above, various body cells have a variety of corresponding receptors called pattern-recognition receptors or PRRs capable of binding specifically to conserved portions of these molecules. Cells that typically have pattern recognition receptors include macrophages (def), dendritic cells (def), endothelial cells (def), mucosal epithelial cells, and lymphocytes (def).
Pattern-reconition receptors will be taken up in the next section.
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Updated: March, 2011
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