I. THE INNATE IMMUNE SYSTEM

D. EARLY INDUCED INNATE IMMUNITY

1. Pathogen-Associated Molecular Patterns (PAMPs) and Danger-Associated Molecular Patterns (DAMPs)

Fundamental Statements for this Learning Object:

1. 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 binding to pattern-recognition receptors or PRRs.
2. Pathogen-associated molecular patterns or PAMPs are molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells. Examples include LPS, porins, peptidoglycan, lipoteichoic acids, mannose-rich glycans, flagellin, bacterial and viral genomes, mycolic acid, and lipoarabinomannan.
3. Danger-associated molecular patterns or DAMPs are unique molecules displayed on stressed, injured, infected, or transformed human cells also be recognized as a part of innate immunity. Examples include heat-shock proteins and altered membrane phospholipids.
4. PAMPs and DAMPs bind to pattern-recognition receptors or PRRs associated with body cells to induce innate immunity.

LEARNING OBJECTIVES FOR THIS SECTION

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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. Innate immunity can be divided into immediate innate immunity and early induced innate immunity. In this section we will learn about immediate innate immunity.

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 pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). 

1. Pathogen-Associated Molecular Patterns (PAMPs) (def) and Danger-Associated Molecular Patterns (DAMPs) (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 danger-associated molecular patterns or DAMPs (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 and mycolic acids 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 (def) 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; and

c. molecules normally located inside phagosomes and lysosomes that enter the cytosol only when these membrane-bound compartments are damaged as a result of infection, including antibodies bound to microbes from opsonization.

d. molecules normally found within cells, such as ATP, DNA, and RNA, that spill out of damaged cells.

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).

 

For More Information: Pattern-Recognition Receptors (PRRs) from Unit 5

 

Concept Map for PAMPs and PRRs

 

TPS Question

 

 

• 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.