Thursday, October 28, 2010

Immune Duality

In order to understand difficult concepts of the immune system, such as the difference between CD4 and CD8 T cells, the difference between MHC I and MHC II HLAs, and the difference between endogenous and exogenous antigen presentation, it helps to first understand that there are two types of “foreign invaders” that your body is trying to fight against.

The first is the extracellular pathogen.  This can be a bacteria or a parasite.  It is a cell, with a cell wall and a cell membrane, and surface antigens.  It infects the body, but doesn’t get into body cells.

See here for a cool movie of a white blood cell chasing and phagocytosing a microbe.  That’s what we’re talking about when we talk about extracellular pathogens.

So the aspects of the immune system that relate to this can be better understood once you have a good idea of what we mean by extracellular pathogen.  The antigen presentation steps include being phagocytosed, and pieces being displayed on the antigen-presenting cell surface.  Also, the way we combat that microbe is to activate the ”extracellular microbe killing machinery” which is the B cells.

The other type of pathogen your body is trying to fight is intracellular pathogens, like viruses.  From the outside, there is no way for your immune system to know if there is a pathogen inside there.  So in this way, the infected body cell takes pieces of proteins that are being made inside the cell, and displays them on the cell surface (in a MHC molecule).  If the protein being displayed is a normal cell protein, then the immune system just moves along to look at the next cell.  If the protein being displayed is abnormal or foreign, then the immune system becomes activated.

So this antigen presentation involves processed proteins being displayed on the cell surface, and the way we combat the microbe is to initiate the “cell killing” machinery, or the cytotoxic T cells.

This T Cell Killing video shows the cell killing taking place after the cytotoxic T cell recognizes the infected cell.

Extracellular pathogens:
Live outside of body cells
Are fought by B cells, antibodies, and Helper T cells (CD 4)
Have to be processed by antigen presenting cells like phagocytes
Their antigens are displayed in the context of an MHC II molecule

Intracellular pathogens:
Live inside of body cells
Are fought by Cytotoxic T cells (CD 8)
Are processed inside the infected cell
Their antigens are displayed in the context of an MHC I molecule

This video summarizes the immune response to infection.

Thursday, October 21, 2010

The Sodium-Potassium Pump

When trying to think of a topic to start with, the Sodium-Potassium Pump came to mind almost immediately.  Maybe because I am getting ready to teach about the Action Potential in A&P I.  Perhaps because I am teaching next about the Urinary system in A&P II.  In any case, it seems like a good place to start, because is a single protein that affects so many functions and processes across a number of different systems.

Remember, as you are looking at textbook figures and viewing animations, that the chemical symbol for sodium ions is Na+, and the chemical symbol for potassium ions is K+.

The sodium-potassium pump is an active transporter.  It is a protein found in the membrane of many cells, including excitable cells like muscle fibers and neurons.  It moves 3 sodium out of the cell and 2 potassium into the cell, and requires the use (hydrolysis) of ATP for the energy to move those ions against their concentration gradients.

See animation here and here.  And of course, there is this video from YouTube.

The sodium-potassium pump creates a concentration gradient, or chemical gradient, for sodium, and one for potassium.  Moving 3 sodium out of the cell on every turn ends up creating a large concentration of sodium on the outside of the cell.  Moving 2 potassium into the cell on every turn ends up creating a large concentration of potassium on the inside of the cell.

In addition to creating these two concentration gradients, the sodium-potassium pump also creates an electrical gradient.  Moving three positive charges out of the cell, but only moving two positive charges into the cell, causes more positive charges to accumulate on the outside of the membrane.

Because of this, we often talk about the "electrochemical" gradients for sodium and potassium. 

So in a normal cell, such as a muscle cell, that has a sodium-potassium pump, you will find the following:
  • More sodium ions outside the cell
  • More potassium ions inside the cell
  • More positive charges outside the cell

And all of that is created by the sodium-potassium pump.