I’ve just found this amazingly well done video of the embryonic formation of the GI tract. I would recommend that my students watch it and concentrate simply on how the structures connect and how they get from a simple tube (shortly after conception) to their form in a fully developed human (i.e. baby -> adults).
Ultimately, this is just a review of basic anatomy. But a damn good one.
Lymphocytes Development and Activation
Lymphocytes (B cells and T cells – we’ll not talk about NK cells here) go through a generalizable sequence of maturation events. Each starts in the Bone Marrow (BM) as a Hematopoietic Stem Cell (HSC), where it starts its development. T cells leave the BM relatively sooner and go to the Thymus, while B cells remain in the BM for most of their development and then finalize development in the spleen.
Positive Selection for BCR/TCR Development
Regardless of the type of cell (T or B), development occurs in two stages – First, each cell will attempt to make a unique lymphoid receptor (B cells have a BCR; T cells have a TCR). In order to do this, genetic material must be shuffled. While this shuffling does randomize the binding pocket of the lymphoid receptor, it may also destabilize these same receptors’ structure. To account for this, lymphocytes undergo a ‘positive selection’ period that ensures that a viable receptor is formed. This is actually done twice: once to ensure that a ‘Pre-Lymphoid Receptor’ is formed and again to for a ‘Mature Receptor.’ However, both are considered positive selection. Failure to pass this selection point leads to death of the cell. (In the figure below, Pre-Lymphocyte receptors are colored red, mature receptors are grey)
Negative Selection Against Self-Reactive BCR/ TCRs
Once cells have survived positive selection, they are considered Immature Lymphocytes. Although the terminology is poor here, these immature cells have mature lymphocyte receptors. At this point, these receptors have to be tested against all possible ‘Self ‘- antigens. In this case, binding means that these cells have the potential to react against the self – this is a no, no. The Immune System turned against the self is extraordinarily dangerous. Therefore, self-reactive cells are eliminated during this negative selection process. (In the figure below, mature lymphocytes have grey nucleus, all prior stages have red nuclei).
Following these developmental stages, the cells that have survived both positive and negative selection are 1) stable, mature lymphocyte receptors and 2) not reactive to ‘self’. These cells then enter the immune repertoire for that organism and are available to react against any foreign threats. Again, it is important to emphasize that each lymphocyte has a unique receptor and therefore will only get activated by a unique foreign antigen.
I may write more later to discuss some of the details that distinguish B and T cell development, but for now, this generalizable description will suffice.
Clonal Selection
Once a part of the immune repertoire, lymphocytes are on the lookout for foreign antigen that is capable of being bound by that cell’s receptor. Depending on the cell type, this interaction may be in one of several contexts (either in the context of MHC I, MHC II or as a naïve, soluble antigen), but regardless of the context, these ‘naïve’ lymphocytes will become activated by binding of their lymphocyte receptor. And once activated, lymphocytes will proliferate and differentiate. Differentiation typically goes in one of two general directions:
1) generating activated effector cells (these secrete antibody if B cells, kill target cells, if CD8 T cells, or become helpers if CD4 T cells)
–or-
2) generating memory cells, cells that act the same as the mature naïve cell that was activated, but are more numerous and can, themselves be activated upon stimulation.
An example of this activation is shown below in this HHMI video about how CD8 T cells can be stimulated to activate and then kill any target cells. This video also does a good job of illustrating how antigens get digested within a cell and expressed in the context of MHC I.
http://www.hhmi.org/biointeractive/media/antigen_ctl-lg.mov
Here’s my first function.
It prompts the user to provide a number of digits from 1-6. It then confirms this with the user – well, really just me for debugging purposes. I also use a Boolean ‘codeVeritas’ to ensure that the number of digits the user enters is within the parameters defined.
//gets the number of digits used
var code = function(){
var enteredCode = 0;
var codeVeritas = false;
//so far the codeVeritas is working fine
while (codeVeritas === false){
console.log(“***code function reached***”);
enteredCode = prompt(“How many digits shall the code be? (1-6)”);
//verify input
if (enteredCode > 0 && enteredCode <= 6){
console.log(“We will be using “+ enteredCode+ ” digits in our code”);
codeVeritas = true;
return enteredCode;
} else{
alert(“number is out of range.”);
}
}};
A quick outline on what we need to do to get a simple app:
1. The hard part (make the app itself – I’ve already posted an outline of the way this might be coded, I’ll certainly spend a lot more time fleshing this out here as we go)
2. Setting up space with apple to publish this app
a. Come up with a good name (I’m thinking of something like ‘codeBreaker’ or safeCracker) and reserve that on iTunes Connect (the developer side of iTunes)
b. Describe the app, put together a prototype with artwork to make screenshots and Icons required in iTunes Connect and certainly required to make the app itself.
Presently, I’ve chosen the name SafeCracker! and made up a quick mock of an icon in powerpoint (shown). You have to have an icon and at least one screenshot to reserve the name with, but you can change these as you go along the process. As I said, I made an icon that will have to be refined and for now, I’m using a screenshot from another app to placehold. You need to add some other details as well in the registration form, but most of those are simply things you can make up on the spot. For instance, I use the 6 digit date as my SKU number.
DownHouseSoftware 