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Antigen Presentation #1: Macrophages

08 Dec

Antigen Presentation

Presentation by Macrophages

Macrophages (‘Big Eater Cells) exist in a variety of flavors with slightly different functions throughout the body. For out purposes, we’ll just consider a macrophage that is responding to some inflammation. Like a number of other cells, macrophages can react to inflammatory signals generated by damaged cells at the site of a wound. Once there, the macrophages will eat up (by phagocytosis) whatever they find : cellular debris, dirt, bacteria, anything.

ImageOnce they take up this material, the macrophages will begin to ‘Process and Present’ them. Processing involves the digestion of internalized material by fusion of the phagosome with enzyme-containing lysosomes and reactive-oxygen-species-containing peroxisomes. This treatment breaks up materials into small units that can be bound by Major Histocompatability Complex (MHC) Class II molecules and transported to the cell surface. In this way, the MHC ‘presents’ antigens(Ag) such that they can be tested for binding with the T Cell Receptors (TCRs) on T Cells.

MHC Class II molecules with Ag can be engaged by TCRs with the aid of CD4 acting as a stabilizing molecule between the T Cell and the MHC. However, only TCRs that can soundly bind the MHC+Ag will trigger a reaction that promotes the T Cell to become activated. These activated CD4 Helper T Cells will proliferate and begin secreting molecules (cytokines) that activate other cells in turn. The interaction of T Cells with APCs occurs across a highly organized ‘immune synapse’ where numerous cell-cell recognition molecules come together (see the fluorescent microscopy image below)

Image

      Borrowed from NobelPrize.org

Helper T Cells provide help to a number of other, effector cells, such as B Cells, Killer CD8 T Cells (also called Cytotoxic T Cells, or CTLs) and macrophages.

It is important to recall that T Cells, like B Cells have undergone negative selection during development so that they only bear TCRs that can bind Non-Self material. Therefore, although self molecules may be presented by APCs, there should be no corresponding  T Cells that recognize these Ags.

Keep in Mind the Big Picture!

To summarize with an example:

  1. A bacteria gets into the host through some wound
  2. The wound stimulates inflammation recruiting Macrophages
  3. Macrophages gobble up the bacteria (endocytosis) in a non-specific manner
  4. Inside the Macrophage, the bacteria is killed and broken into a bunch of little pieces
  5. The little bacteria pieces are picked up by MHC II molecules
  6. MHC II molecules move to the cell surface and ‘present’ antigen
  7. T Cells with TCRs capable of binding this bacteria piece within MHC II, do so
  8. These T Cells become activated, proliferate and produce activation factors (cytokines)
  9. These activated T Cells can now go on to ‘help’  (primarily) B Cells and CD8 ‘Killer’ T Cells  do their jobs

The Immune Synapse

Image

HTLV-I capsid protein (Gag) at the cell-cell 
junction. Tubulin-alpha (green), HTLV-I Gag p19 (red). 
Bar = 5 μm. Source

 

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Posted by on December 8, 2013 in Uncategorized

 

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