Microbiology, Lec. 20.

Chapters 27 & 28. More on defense of the body

Figure 27.1 shows the different kinds of barriers to microbial attack (we have already mentioned the first 2 nonspecific responses).

I want to talk about immunology just enough so that we can understand the basics of how the immune system responds to microbes and viruses.

Antigens are specific molecules to which the immune system responds. Basically, our immune system can tell a foreign cell from one of our own cells based on the antigens on the surface of each cell type. Common antigens are molecules found on the outside of cells (or viruses). Some examples are the polysaccharide portion of the lipopolysaccharide (LPS, Figure 4.51, lec. 4) in the outer membrane of gram - bacteria. Other antigens include pili, flagella, capsule polysaccharides, porin proteins (lec. 4) and exotoxins (lec. 21). The outer proteins of viruses are also good antigens. Almost any protein greater than 1000 daltons in size can be an antigen and most antigens are proteins.

Antigen-Binding molecules. Most of these guys belong to the immunoglobulin superfamily of molecules. Figure 27.10 shows the four main types of immunoglobulins. These molecules function as the feelers that detect and bind to antigens. Don't memorize all the different types of immunoglobulins....I'll point out some important points on Figure 27.10 and other figures as we go along. Note that the B-cell antigen receptors can also act as antibodies. Antibodies are just immunoglobulins that are released by specific types of B-cells.

Let's look at the left side of Figure 27.12. The main idea is that as the bacterium is digested during phagocytosis antigens are released from the bacterium and these bacterial antigens are bound by specific immunoglobulins (MHC-II). The Antigen-MHC then migrates to the surface of the macrophage (Figure 27.22), where a helper T-cell binds to the complex and secretes factors that stimulate specific B cells.

The B-cells then multiply into Plasma cells and Memory B cells (Figure 27.26). The plasma cells are short-lived and produce billions of antibodies for the specific antigen that was presented by the macrophage. What do you suppose the memory B-cells do?

Destruction is carried out by: (see Figure 28.1)

1) The Complement System which makes transmembrane protein channels in marked cells.

2) Increased phagocytosis. The binding of antibodies and complement protein C3 make it easier for phagocytes to find and attach to bacteria. The coating of bacteria with antibodies and C3 is often called opsonization.

So now that you understand some of the process, let's go back to the beginning of chapter 27 and look at Figure 27.3. This is where the Memory B-cells come in.....

We have talked about one way that a bacterium can stimulate an immune response above (i.e. via antigen presenting cells, helper T cells etc.). Some antigens (e.g. some exotoxins and very exposed antigens like flagellar proteins) can also stimulate B-cells directly. The end response is pretty much the same, the production of a lot of antibodies for the specific antigen.

Viruses can also set off an immune response. When free in the body they can lead to the production of antibodies. These antibodies then coat the virus which prevents it from binding to receptors on our cells. Antibodies also act as opsonins on viruses thus increasing their susceptibility to phagocytosis or attack by various killer cells.

Once viruses infect our cells they can also be subject to attack by the immune system. This is because most proteins that are produced in cells are also presented on the surface of the cell by immunoglobulins (MHC-I). Cells of our immune system therefore can tell if a cell is making foreign proteins and destroy that cell (using cytotoxic T cells, NK cells etc. see Figure 28.4). Thus, the bodies last line of defense against viruses is to destroy all our own cells that are infected with them!

Secretory Antibodies

Certain antibodies (IgA) can be secreted at mucosal surfaces. Fig. 28.12 illustrates how these antibodies help to protect mucosal surfaces by 1) carrying antigens into the intestines, throat etc. where the antigens can be carried out of the body, or
2) binding to antigens near the mucosal surface (e.g. in the intestinal lumen) and thereby preventing them from attaching to our mucosal cells.