Active Immunity for the USABO, Part 1 (will help you connect the dots if you’re reading Campbell’s immune chapter and are lost)

Idea creds @Delphinidin.

Let’s discuss how active immunity operates during infection and reinfection. Before we start, let’s define the term antigen-presenting cell (APC). An APC is any cell that presents antigens in any scenario. Most commonly, “APC” refers to macrophages and dendritic cells that phagocytose and process the pathogen (basically eat it and chew it up into pieces) to create antigens. They then present these antigens to other cells and begin the infection-fighting process.

All APCs have both kinds of major histocompatibility complexes (MHCs): MHC I and MHC II. All other nucleated body cells have MHC I. Anucleated cells (no nucleus) such as red blood cells do not have MHC proteins. MHCs basically just help APCs bind to and present antigens.

Now that we have the background info, let’s get to it.

During the first exposure to the pathogen, APCs phagocytose the pathogen to create antigens. APCs present these antigens to both helper T cells (Th) and cytotoxic T cells (Tc). APCs use MHC I to connect with Th cells and MHC II to connect with Tc cells, in order to present the antigen. Similarly, Th and Tc cells also contain components to facilitate this bond: Th use CD4 to connect with the APC’s MHC II, and Tc use CD8 to connect with the APC’s MHC I. Hence, Th cells are also called CD4+ cells, and Tc are CD8+. Here’s what that looks like:

APC activating Th.

APC activating Tc.

In the image above, there is something very important to notice: while the Th is activated by a normal APC like a macrophage or dendritic cell, the Tc is activated by an infected cell (which has MHC I instead of II as it is a normal body cell, not a specialized APC). Technically, the infected cell also counts as an “antigen-presenting cell” because it’s presenting an antigen. It’s important to remember that the definition of an APC is flexible.

This difference makes sense with the function of Th versus that of a Tc. Th get the signal about what the antigen looks like, and help activate downstream immune responses. Tc resort to direct kills. Upon Tc activation by an infected cell (or by cytokines released by a Th cell), Tc cells release granzymes and perforins to induce apoptosis and poke holes in infected cell membranes, respectively. Granzyme function is also perforin-dependent.

So far, we’ve discussed how antigens activate Tc and Th cells. Now, let’s discuss B cells. B cells can be directly activated by antigens in some cases, without the need for an APC. Also, like Tc cells, B cells can be activated by Th cells. Here’s what that looks like:

Notice that the B cell has MHC II, indicating that it is a special kind of APC that falls under the same category as macrophages and dendritic cells. Also notice the CD4 coming from the Th: no matter what’s on the other side, Th cells will connect to whatever it is using CD4.

B cells become plasma cells and produce antibodies against the antigen they are presented with/have processed. 

That’s part 1 of this topic. Part 2 will tie everything together and talk about reinfection. Hope this was helpful!

Here’s part of a summary pic I drew (part 2 will have the whole thing):