ADCC, Antibody-Dependent Cell-Mediated Cytotoxicity. It's enough to make you cry after countless hours trying to study something only vaguely familiar however, the picture on slide 106 of our pathology power point presentation shows a picture of ADCC and a few elements of confused gases swirling around in my brain have begun to form into something that makes sense based on that picture. I'll post the picture as today's pic of the day.
The human immune system is based on a system of surveillance operating on the simple principle of distinguishing "self" from "non-self" In other words, we have a variety of "soldier cells" capable of destroying other cells and pathogens (foreign bodies) but, these soldiers which protect us need to be able to tell the good guys from the bad guys.
Take a close look at that picture. In it we see the cell in the upper left labeled as a Target cell. Now, this Target would be the bad guy which needs to be taken out BUT - that target very well may have been one of us, a good guy that's gone over to the dark side and now needs to be taken out. In this sense, we come to realize that an individual cell has been infected by some foreign invader, be it H1N1, or even the Aids virus. When a cell is taken over by a hostile (i.e., foreign invader) it may burrow down to the core of the cell and take over the protein processing factory in the cell which we may refer to as the nucleus of the cell.
As an analogy, let's say the nucleus of General Motors is an assembly plant to make cars and a foreign invader comes in and rewrites some of the instructions for making those cars. Let's say instead of using hard plastic for the gas pedals the invader rewrites the instructions to use chewed bubble gum instead of hard plastic for those gas pedals. Then, when those cars are released into the rest of the world and are driving on our highways there are going to be problems.
Basically, whatever was supposed to be produced in that nucleus isn't being properly produced anymore. Heck, maybe instead of cars being produced things might be rewritten to manufacture horse & buggy carriages which again will mess things up by clogging up the highways.
The thing is, when a normal cell from the human body is taken over then there may be tell tale signs that the cell has been compromised. If you look at the picture again, you'll notice spikes protruding out of the membrane of the cell. Now, notice the little black "Y" shaped things floating around in the picture. Those are antibodies. In fact, those are antibodies which are specific to the spikes sticking out of the compromised (Target) cell. The cell at the right side of the picture shows the target cell with the antibodies attached to the spikes of the target cell and THIS is how the cell is labeled for destruction.
The cell at the bottom most portion of the picture is labeled an NK cell. NK stands for Natural Killer and the NK cell has receptor type locks on it's membrane which fit to those particular antibodies. Think of a lock and key. The antibody may be the key and the receptor on the NK cell may be thought of as the lock. When that antibody key clicks w/ the Natural Killer cell lock then the NK cell may take action to destroy the Target cell.
hmmmm.....
That's one way NK cells are able to identify the bad guys in the human body but, how do they know which cells to pass over?
Almost every cell in the human body has what are known as Class I MHC molecules on the surface of their cells and Killer cells have an inhibitory receptor on the surface of their cells which fits with the Class I MHC molecules. Again, we have another key & lock scenario. When the inhibitory receptor lock meets with a Class I MHC key then the Killer cell knows those cells are part of us and moves on.
I think of the movie The Ten Commandments with Charlton Heston as Moses (can you believe that was made in 1956?!) Anyway, during part of that movie there was some kind of plague destined to go through the town and kill children or something but, houses which had blood on the door were passed over by the plague. I'm not sure how accurate I have the movie but, those Class I MHC molecules are like the blood on the door - Killer Cells just pass them by.
ADCC - that's where we started this conversation and remember the AD stands for Antibody dependent. From what I'm understanding immunoglobulins are another type of antibody ...immunoglobulins are designated IgG, IgM, IgA, IgE & IgD.
When it comes to IgG, in particular, I'm thinking of how the military can light up targets with a laser so overhead airplanes can drop bombs on the target. IgG can coat bad cells and there are receptors on Natural Killer cells that can recognize an IgG coating. These receptors are called CD16 & Fc receptors.
CD16? What does the CD stand for? Good question, I don't know. Let me Google it...
That was worthwhile, it looks like CD stands for Clusters of Differentiation :)
here is a link to wikipedia with an incomplete list of 300 or so differend CD molecules.
Talk of CD molecules, which help differentiate cells, are found on the surface or membrane of our cells. There are a few we've covered in class...
CD3 is a molecular complex used for cells to identify T-Lymphocytes which make up about 60-70 percent of the lymphocytes in our blood. Each T cell is genetically programmed to recognize certain membrane bound antigens. So far, I've presupposed antigens can be good or bad depending on whether they are recognized by the body or not as "self" or "non-self" Wikipedia mentions the word Antigen as coming from "antibody generation" which may or may not be true but, it's something to hang my hat on for now.
CD3 is a series of molecules that help relay information into a cell once a T-Cell has connected to an antigen binding site on the cell.
For now and in general - I'm relating things as follows ...
CD3 - T lymphocytes
CD4 - helper T cells
CD8 - T-suppressor or T-cytotoxic cells
CD16, CD56 & Fc go w/ Natural Killer Cells
CD 18+, CD19+, CD20+ go w/ B-Lymphocytes
then we need to recall that with helper T cells there are two subpopulations
T-helper-1
T-helper-2
and, I need to have those associated with things.
Namely,
T-helper-1 goes w/ Interleukin-2 (IL-2) and Interferon gamma (IFN-g)
T-helper-2 goes w/ Interleukin 4 & 5 (IL-4 and IL-5)
Then, we need to get back to the various markers on the regular cells of the body, at least that's where I think the following classes of molecules are found.
We mentioned MHC molecules earlier. MHC stands for Major Histocompatibility complex or for humans, we may also say (or use) HLA which stands for Human Leukocyte Antigen.
We have three classes of MHC -
Class I MHC consist of
HLA-A
HLA-B
HLA-C
and, of course, there are subpopulations of those things
Class II MHC consist of
HLA-DP
HLA-DQ
HLA-DR
or, you might broadly say Class II is associated with D and class I is associated with A, B, C (for memory purposes anyway)
Class III has to do with components of the Complement system and here we associated C2 & C3 with Class III.
Pretty vague & a bit confusing, huh? I hear ya.
I guess a main thing to take away from all these HLA things is that they are markers found on cells and tissues in the human body and one of the most important thing having to do with these markers is in the area of transplants. Most folks are aware that people have different blood types and it's not good to randomly mix peoples blood types because bad things can happen if you do.
Well, it's not a good thing to mix HLA's either. The liver or kidney of one person will have a specific set of HLA markers in the cells which make up their liver or kidney and they can only get a transplant from a person who has similar HLA markers. To mix those markers up means rejection of the transplanted organ.
Also, there are some interesting correlations between different HLA markers and various diseases. For instance, a person with HLA-B27 has a 90 times greater risk of ending up with a disease known as Ankylosing Spondylitis. What is ankylosing spondylitis? I honestly don't know, at this point I just need to konw that HLA-B27 is associated with a 90 times greater risk of ending up with that disease.
Rheumatoid Arthritis is associated with HLA-DR4 and type 1 diabetes is associated with HLA-DR3 and HLA-DR4.
Wow - time flies when you're having fun. I need to take off in 15 minutes to meet my parents for lunch! :D
Thank god - I need a break and decompression time. ;)
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