Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online

CHAPTER 5 - BINDING

F:   IMMUNE SYSTEM RECOGNITION

BIOCHEMISTRY - DR. JAKUBOWSKI

Last Updated: 03/14/13

Learning Goals/Objectives for Chapter 5E:  After class and this reading, students will be able to

  • under development

F5.  Recognition and Response in the Innate Immune System

The adaptive immune response must be activated by cells of the innate immune system. These cells must recognize viruses and living cells like bacteria, fungi, and protozoans like amoebas.  There are often common structural features in these different classes of cells.   The cells of the innate system (dendritic cells, macrophages, eosinophils, etc) have receptors (Toll-like Receptors 1-10 or TLRs) that recognize the common pathogen associated molecular patterns (PAMPs) , which leads to binding, engulfment, signal transduction, maturation (differentiation), antigen presentation, and cytokine/chemokine release from these cells.  Take for example dendritic cells, which reside in the peripheral tissues and act as sentinels.  They can bind PAMPs which include:

  • CHO/Lipids on bacteria surface (LPS)
  •  mannose (CHO found in abundance on bacteria,
  • yeast dsRNA (from viruses)
  • nonmethylated CpG motiffs in bacterial DNA

Bacterial and viral nucleic acids are recognized by intracellular TLRs in the cell after the they been taken up into the cells by endocytosis.  Dendritic cells phagocytize microbial and host cells killed through programmed cell death (apoptosis).  In the process of  maturation, surface protein expression is altered, allowing the cells to leave the peripheral tissue and migrate to the lymph nodes where they activate T cells through the antigen presentation methods described above.  They also control lymphocyte movement through release of chemokines.  The very large figure below shows the processes involved in recognition of PAMPs by TLRs of innate immune system cells.

 A model of dsRNA interacting with the ligand binding domain of TLR3 is shown below. 

Jmol: Updated TLR3:dsRNA complex Jmol14 (Java) |  JSMol  (HTML5)  Needs updating

 

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