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innate immunity

Wednesday 24 November 2004

The innate immune system provides the host with an immediate and rapid defense against invading microbes.

Detection of foreign invaders is mediated by a class of receptors that are known as the pattern recognition receptors, such as the family of Toll-like receptors (TLRs).

Pattern-recognition receptors, such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), are able through the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns to sense microbe-dependent and microbe-independent danger and thereby initiate innate immune responses.

Toll-like receptors (TLRs)

In humans, ten functional TLRs have been identified and they respond to conserved pathogen-associated molecular patterns derived from bacteria, mycoplasma, fungi and viruses. TLR activation leads to direct antimicrobial activity against both intracellular and extracellular bacteria, and induces an antiviral gene program.

TLR2 activation leads to the use of vitamin D3 as a mechanism to combat Mycobacterium tuberculosis.

Pathology

In some autoinflammatory conditions, abnormalities in NLR signaling pathways and NLRs are involved in pathogenesis, as exemplified by NOD2 mutations associated with Crohn’s disease. Some other NLRs are components of the inflammasome, a caspase-1- and prointerleukin-1beta-activating complex.

The inflammasome has a central role in innate immunity. Some monogenic hereditary inflammatory diseases, such as Muckle-Wells syndrome, are associated with mutations in proteins that modulate the activity of the inflammasome, and on some multifactorial disorders, such as Type 2 diabetes and hypertension.

See also

- innate immune responses
- innate immune system
- innate immunity
- TLR recptors (TLRs)
- non-TLR receptors

References

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- Marques JT, Carthew RW. A call to arms: coevolution of animal viruses and host innate immune responses. Trends Genet. 2007 Jul;23(7):359-64. PMID: 17467114

- Liu PT, Krutzik SR, Modlin RL. Therapeutic implications of the TLR and VDR partnership. Trends Mol Med. 2007 Feb 2; PMID: 17276732

- Comalada M, Peppelenbosch MP. Impaired innate immunity in Crohn’s disease. Trends Mol Med. 2006 Sep;12(9):397-9. PMID: 16890491

- Williams AP, Bateman AR, Khakoo SI. Hanging in the balance. KIR and their role in disease. Mol Interv. 2005 Aug;5(4):226-40. PMID: 16123537

- Bokoch GM. Regulation of innate immunity by Rho GTPases. Trends Cell Biol. 2005 Mar;15(3):163-71. PMID: 15752980

- Ohteki T. Critical role for IL-15 in innate immunity. Curr Mol Med. 2002 Jun;2(4):371-80. PMID: 12108948

- Soloski MJ. Recognition of tumor cells by the innate immune system. Curr Opin Immunol. 2001 Apr;13(2):154-62. PMID: 11228407