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Antigen Presentation #2: B Cells

Antigen Presentation

Presentation by B Cells

Before thinking about B Cells presenting antigen, first recall that B Cells are lymphocytes bearing antigen receptors on their surface called B Cell Receptors (BCRs). These BCRs have been randomized during development such that every B Cell can theoretically bind a unique antigen. See Lymphocyte Development for a refresher on this if you need it.  The major function of B Cells is to make antibody that is nearly identical to its receptor protein, which will be secreted and can then bind to antigens of the same shape.

Image

B Cell with specific BCR engages an antigen on a bacterium (Left). After activation this B Cell will become a Plasma Cell secreting antibody with identical specificity as the original BCR (Right).

A major distinction between B Cell phagocytosis and that by Macrophages is that B Cells only take up materials they have bound with their BCRs, while macrophages take up material indiscriminately. The reason for this, of course, is that B Cells are gearing up to produce antibody, and the best way to ensure this antibody will bind anything of use is if only B Cells bearing specific BCRs known to bind antigen are activated. Macrophages have no antigen-specific receptors, so this specificity is not required by those cells. The membrane bound BCR is exactly the same molecule as secreted antibody – except for the small portion that anchors the BCR to the membrane.

Like macrophages, B cells are ‘professional’ antigen presenting cells (APCs) that take up exogenous antigen, break it down within lysosomes and present the resulting peptide fragments within MHC Class II Molecules. As with other professional APCs, this is intended to pick up foreign, invasive particles for present them to T cells to elicit a specific immune response.

ImageJust by binding to antigen with their BCRs, the B Cell will become (at least partially) activated, stimulating proliferation of this cell and processing/presentation of antigen as indicated above. In order to complete its activation, this B Cell must receive ‘help’ from T Cells capable of binding the presented antigen in the context of MHC II. Because T Cells have also been selected for ‘Non-Self’ exclusivity, this provides additional insurance that this B Cell was truly activated by a ‘Non-Self’ antigen.  The MHC II :: TCR + CD4 interaction between the antigen-presenting B Cell and the helper T Cell results in activation of the T Cell, that immediately gives activation signals (cytokines) back to the B Cell.

 

Keep in Mind the Big Picture!

To summarize with an example:

  1. A bacteria gets into the host
  2. B Cells with BCRs capable of binding any part of that bacteria catch ahold of it
  3. These B Cells gobble up the bacteria (endocytosis)
  4. Inside the B Cell, 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 activation factors trigger the B Cell to go on proliferating and changing into Plasma Cells.

10. Plasma Cells no longer make BCR on the surface, they make a soluble form of that BCR, called Antibody, and spew that forth in great amounts.

11. Antibody can coat, gum up, and signal the disposal of bacteria all over the body.

Resting and Activated T Cells from “Immune System History” by Dr. Harry Louis E. Trinidad 
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All that ER expansion is to accommodate the heavy load of secreted protein this cell will churn out.

 

 

 
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Posted by on December 8, 2013 in Uncategorized

 

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Antigen Presentation #1: Macrophages

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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Three posts on Antigen Presentation

Having recently finished teaching a semester of microbiology ending with my favorite topic, immunology, I thought I would provide some summaries of three different types of antigen presentation:

1. Presentation of antigen by macrophages (MHC II + Ag) to CD T Cells (TCR + CD4) resulting in the activation of CD4+ Helper T Cells

2. Presentation of antigen by B Cells (MHC II + Ag) to CD T Cells (TCR + CD4) resulting in the activation of CD4+ Helper T Cells – specifically capable of activating B Cells that have ‘seen’ and taken up antigens that bind to their unique BCRs.

3. Presentation of antigen by Epithelial Cells (MHC I + Ag) to CD T Cells (TCR + CD8) resulting in the activation of Cytotoxic T Lymphocytes (CTLs) that will kill cells presenting this antigen. All Cells bear MHC I, enabling them to present endogenous, intercellular antigens such as infecting virus particles.

 
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Posted by on December 8, 2013 in Uncategorized

 

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