Microbiology, Lec. 21.

Announcements:

Upcoming Micro. Seminars

Tuesday, April 10 from 3:30 - 5 pm in Ekeley S274.

Dr. Don Klein, CSU
"Non-discrete microbes in a discrete world"
and
Dr. Angela Bielefeldt, Environ. Eng., University of Colorado
"Effects of biofilms on sub-surface hydrodynamics"

The Immune Response

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 (Immunogens) 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, e.g. the O side chain or O antigen of Salmonella (see pg. 55, Fig. 3.27, and lec. 3) in the outer membrane of gram - bacteria.
Other bacterial antigens include pili, flagella (lec. 4), capsule polysaccharides, porin proteins (lec. 3) and exotoxins (lec. 23).
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.

Antigenic Determinants (=Epitopes, see pg. 610)

Antigen-Binding molecules (Antibodies). Most of these guys belong to the immunoglobulin superfamily of molecules. Figures 30.8 - 30.10 shows the main types of immunoglobulins. These molecules function as the feelers that detect and bind to antigens and as free circulating antibodies. Don't memorize all the different types of immunoglobulins....I'll point out some important ones 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 (see below).

How do antigenes cause antibody production?

So now that you understand some of the terminology, let's go to Figure 30.17.

Know...

B-cell types (Plasma and Memory) and relate to primary and secondary antibody responses (Fig. 30.18)
Vaccines and vaccination (See Fig. 30.18 and read Box 30.2)

How do microbial antigens trigger an immune response?

Let's look at Figure 31.4. 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, 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 (see above). The plasma cells are short-lived and produce billions of antibodies for the specific antigen that was presented by the macrophage.

All of those antibodies can then bind to the same kind of antigen and essentially mark cells with those antigens for destruction.

Destruction is carried out by:

1) The Complement System which makes transmembrane protein channels in marked cells (see Figures 32.2 and 32.3).

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 (opson is Gr. for prepare victims for.., pg. 661). Review Figure 32.6.

See lec. 20 for discussion of phagocytosis

A few more tidbits about the immune response

I. Response to Viruses

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., see above). Viruses can also set off an immune response (see Fig. 31.8). These antibodies then coat the virus which prevents it from binding to receptors on our cells (see Fig. 32.4). 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. seeFigures 31.8 and 32.5). Thus, the bodies last line of defense against viruses is to destroy all our own cells that are infected with them!

II. Neutralization Reactions

See Figure 32.4

III. Secretory Antibodies

Certain antibodies (IgA) can be secreted at mucosal surfaces (See lec. 20).

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 (see Neutralization above, Fig. 32.4).