Toll-like Receptor ?

               

    

1.    Toll like receptor are a type of receptor of inmate immunity.

2.    They are also known as pattern recognition protein because they can recognise a specific pattern associated with pathogen which are known as pathogen associated molecular pattern.

3.    This type of receptors is not generated by VI-VDI recombination like TCR and BCR.

4.    It recognises following type of pattern associated with pathogen.

Example: -

Toll like receptor	Pattern associated mol. pattern
TLR-2	Cell wall compound of Gram-positive bacteria, LPS and yeast cell wall component.
TLR-3	ds RNA
TLR-4	LPS
TLR-5	Flagellin

Disease associated with TLR (TLR-4) septic shock syndrome: -

1.    The specific shock syndrome generally results from LPS release from many Gram-negative bacteria.

2.    The pathophysiology is very complex and not completely understood.

3.    The people at with developing septic shock including those who are hospitalise with chronic illness and poor nutritional status.

4.    The risk is highest after the invasive procedure like subquery it also develops in immune compromised adults.

5.    The septic shock begins with infection of pathogen in the blood.

6.    Once the pathogen appear in the blood their LPS is released, release of LPS occur during cell division of bacteria and also upon its killing.   (LbP)

7.    In the blood lipid and part of LPS binds to lipid binding protein

8.    To the lipid A complex of LPS is then transfer from LbP to CD₁₄ present on mΦ and dendritic cells.

9.    CD₁₄ then transfer lipid A to MD₂ (myeloid differentiating protein 2) after binding to lipid A Md₂ undergoes conformational changes and leads activation and dimerization of TLR-4

10.                   Activated TLR-4 induce activation of signal transducton pathway in which a transcription factor NFKB is activated.

11.                   NFKB helps in expression of gene of proinflammatory cytokines which induces TNF-α, IL and TL6 those cytokines affect vascular coagulation and inflammatory response which ultimately leads to septic shock.

12.                   The combine effect of this cytokine is widespread vasodilation, myocardial pump failure and multiorgan failure

13.                   The overall signal are as follows-

Signal: -

Hypotension (low BP)

Rapid respiration (high pulse rate)

Skin-pales and cold

Diarrhea

Wild spread blood clotting

High WBC count

Capillary leakage    _ Abnormal body temperature

Tissue injury

Lethal organ failure

Treatment: -

Neutralization of TNF and IL with the help of monoclonal antibody and use of antagonistic which prevent fetial shock development.

Reference: -

1.   Mahla RS, Reddy MC, Prasad DV, Kumar H (September 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi:10.3389/fimmu.2013.00248. PMC 3759294. PMID 24032031.

2.  ^ Jump up to:^a b Hansson GK, Edfeldt K (June 2005). "Toll to be paid at the gateway to the vessel wall". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (6): 1085–7. doi:10.1161/01.ATV.0000168894.43759.47. PMID 15923538.

3.  ^ Delneste Y, Beauvillain C, Jeannin P (January 2007). "[Innate immunity: structure and function of TLRs]". Médecine/Sciences. 23 (1): 67–73. doi:10.1051/medsci/200723167. PMID 17212934.

4.  ^ Takeda K, Akira S (January 2005). "Toll-like receptors in innate immunity". International Immunology. 17 (1): 1–14. doi:10.1093/intimm/dxh186. PMID 15585605.

5.  ^ Jump up to:^a b c Medzhitov R, Preston-Hurlburt P, Janeway CA (July 1997). "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity". Nature. 388 (6640): 394–7. Bibcode:1997Natur.388..394M. doi:10.1038/41131. PMID 9237759.

6.  ^ Jump up to:^a b Sharma N, Akhade AS, Qadri A (April 2013). "Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells". Journal of Leukocyte Biology. 93 (4): 521–8. doi:10.1189/jlb.0712328. PMID 23345392.

7.  ^ Rolls A, Shechter R, London A, Ziv Y, Ronen A, Levy R, Schwartz M (September 2007). "Toll-like receptors modulate adult hippocampal neurogenesis". Nature Cell Biology. 9 (9): 1081–8. doi:10.1038/ncb1629. PMID 17704767.

8.  ^ Du X, Poltorak A, Wei Y, Beutler B (September 2000). "Three novel mammalian toll-like receptors: gene structure, expression, and evolution". European Cytokine Network. 11(3): 362–71. PMID 11022119.

9.  ^ Chuang TH, Ulevitch RJ (September 2000). "Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9". European Cytokine Network. 11 (3): 372–8. PMID 11022120.

10.                  ^ Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, et al. (March 2004). "Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection". Proceedings of the National Academy of Sciences of the United States of America. 101(10): 3516–21. Bibcode:2004PNAS..101.3516T. doi:10.1073/pnas.0400525101. PMC 373494. PMID 14993594.