Cell-Mediated Immunity

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What is cell-mediated immunity?

    It means that whatever is invading our body is attacked and either phagocytosed or lysed by cells (without the aid of antibodies).

    Typically, when students are first taught about phagocytosis, they are told that macrophages in the body can ingest bacteria and destroy them.  That is true.  However, how does a macrophage know what is harmful (and should be ingested through phagocytosis) and what is not?  How can our bodies get rid of cancerous cells that are too large to phagocytose?  And can't quite a few cell types actively phagocytose invaders? 

    I will try to answer these questions in the text below.  Keep in mind that multiple cell types can be involved in cell-mediated immunity (CMI).  As you read, you will learn that all types of T cells, macrophages, and other cells called natural killer cells are all involved in CMI.

How do we recognize invaders?

MHC proteins identify cells that belong

    It would be too difficult for all of our immune cells to be able to recognize all the different types of invaders that might affect us.  You will see in antibody-mediated immunity (AMI) that antibodies (and B cells) actually recognize our invaders.  However, for CMI, all our cells have to do is recognize themselves.   Every cell in our bodies has a specific marker on its membrane, called MHC, that serves as an ID marker that it belongs in our bodies.  MHCs of Class I are on every cell, while MHCs of Class II are only on APCs and lymphocytes.

    You see, if a T cell is running around and encounters MHC Class I on every cell it bumps into, it recognizes every cell as belonging in the body, and no immune response will occur.  However, if a T cell runs into a cell that doesn't display an MHC, the T cell will immediately know that that cell doesn't belong in our bodies; the cell-mediated immune response will then begin, and the foreign cell will be destroyed.

    What is MHC?  MHC stands for major histocompatibility complex.  MHC is a complex of protein that projects from the cell membrane into the world.  You know that membrane is made up of both lipid and protein.  And you have already learned about how proteins can run all the way through the membrane and project into the extracellular space; for example, you learned about hormone receptors that are embedded in cell membranes and bind the hormones that encounter them after leaving the blood.

    MHC isn't a receptor.  But it does stick out of the membrane.   Having MHCs on the cell membrane is like having each cell wearing a sign that says "I belong here."

    There are actually quite a few types of MHCs for each class, and these proteins are rather complex.  We're not going to worry about that here.  Just the two main classes.

What are the steps in destroying foreign cells and viruses?

    There are really four steps in cell-mediated immunity.  They are:

  1. antigen presentation
  2. antigen binding (recognition)
  3. co-stimulation
  4. destruction of infector

Let's go through each.

Antigen presentation

    If a bacterial cell, for example, were in our bodies and was recognized as non-self (because it lacks MHC), it would be ridiculous for us to let it hang around until it ran into the right T cell (the one with the matching receptor for that antigen).  If we let it hang around, the bacterial cell would keep dividing and dividing and spreading through our bodies.  Therefore, we have to attack it right away.

    Of course, bacteria can grow so readily in our bodies, that by the time we find one, there are probably many other bacteria there, too.  So, simple destruction of that one bacterial cell wouldn't cut it because it would have already divided and left us a whole set of progeny within our bodies.

    The cells that are most likely to encounter the foreigners first are the macrophages.  When macrophages encounter a foreigner, they phagocytose it right away.  But they still have to hype up our immune system for that particular antigen... so macrophages keep bits of the foreigner's cell markers and display those bits on the surface of their own macrophage membrane.

    Displaying a foreign antigen on a native cell membrane is the "presentation" of the antigen.  It allows the antigen to be seen, but in a safe method, decreasing the chance of spread of infection.  And macrophages can crawl around to where lymphocytes are located to keep the immune response going.  So in order to do "antigen presentation," we have to first phagocytose the foreign item.

Antigen recognition

    This is the step when the lymphocytes get involved.  T cells that encounter the macrophages that are presenting the antigen can now become activated.  You see, the receptors on the surface of the T cells can bind with the antigen on the macrophages and kick into high gear.

Co-stimulation

    Once the macrophage and the T cells interact, they begin to release cytokines.  Cytokines are chemicals that each cell secretes into the environment that typically evoke a localized response (but may also cause widespread responses like fever).

    The effect of cytokine release can include increased phagocytotic activity (more macrophages and neutrophils enter the tissues), T cell proliferation, T cell differentiation, and even more cytokine secretion.

Destruction of infector

    True, we have already seen that macrophages can destroy bacterial infectors.  Neutrophils can also phagocytose foreigners.  But T cells do some things, too.

    What if the infection is viral or a cancer cell?  Viruses infect our own cells, so we have to actually kill our own cells to destroy them, and cancer cells are messed up cells of our own type.  Also, our own cells are rather large to phagocytose.  Instead, certain cytokines can cause T cells to differentiate into cytotoxic T cells.  When cytotoxic T cells encounter cells that need to be destroyed, they secrete a substance called perforin.  Perforin penetrates through membranes and punches holes in cells, killing them.

    Some cytokines that T cells secrete also cause cells to undergo suicide.  This is also a good way to get rid of infections.  Right?  And cytokine secretion can also influence other T cells and macrophages to secrete more cytokines.

2011 STCC Foundation Press
written by Dawn A. Tamarkin, Ph.D.