Pathogen-associated molecular pattern

Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus, protect the host from infection.

This initiation of the immune response consists of the secretion of inflammatory cytokines and chemokines. PAMPs can initiate the maturation of immune cells, which can travel to the primary lymph node and trigger the adaptive immune system that involves the production of antibodies against specific antigens.

Although the term "PAMP" is relatively new, the concept that molecules derived from microbes must be detected by receptors from multicellular organisms has been held for many decades, and references to an "endotoxin receptor" are found in much of the older literature. The recognition of PAMPs by the PRRs triggers activation of several signaling cascades in the host immune cells like the stimulation of interferons (IFNs) or other cytokines.

Cells that promote innate immunity (dendritic cells, macrophages, neutrophils, and more) express PRRs. Not only do PPRs detect PAMPs, they also detect host-derived damage-associated molecular patterns or DAMPs that are products of tissue damage. Toll-like receptors (TLR), complement receptors (CR), and scavenger receptors are among the many types of PRRs that monitor the cellular environment for invaders and damage. The innate and adaptive immune systems are connected through TLRs because it leads to the secretion of cytokines and chemokines that go on to help recruit lymphocytes.

When an antigen breaches the protective barrier (skin, body hair, gastrointestinal tract, etc) and enters the tissue or the bloodstream, the initial response is known as the innate immune system. PAMPs are critical to the initiation of the innate immune system because they recognize the danger, which will result in a response against the threat. PAMPs interacting with PRRs initiate signaling pathways that produce chemokines and pro-inflammatory cytokines–creating an inflammatory environment.

The cytokines and chemokines secreted lead to the translocation of dendritic cells that activate T cells, which "help" B-cells secrete antigen-specific antibodies, which is associated with the adaptive immune response. None of these events can occur without the PRR–PAMPs interaction.

A vast array of different types of molecules can serve as PAMPs, including glycans and glycoconjugates. Flagellin is also another PAMP that is recognized via the constant domain, D1 by TLR5. Despite being a protein, its N- and C-terminal ends are highly conserved, due to its necessity for function of flagella. Nucleic acid variants normally associated with viruses, such as double-stranded RNA (dsRNA), are recognized by TLR3 and unmethylated CpG motifs are recognized by TLR9. The CpG motifs must be internalized in order to be recognized by TLR9. Viral glycoproteins, as seen in the viral-envelope, as well as fungal PAMPS on the cell surface or fungi are recognized by TLR2 and TLR4.

Bacterial lipopolysaccharides (LPSs), also known as endotoxins, are found on the cell membranes of gram-negative bacteria, are considered to be the prototypical class of PAMPs. The lipid portion of LPS, lipid A, contains a diglycolamine backbone with multiple acyl chains. This is the conserved structural motif that is recognized by TLR4, particularly the TLR4-MD2 complex. Microbes have two main strategies in which they try to avoid the immune system, either by masking lipid A or directing their LPS towards an immunomodulatory receptor.