7.6 Overview of the Vertebrate Immune System

Why we care about MHC proteins

In this section and the next one, we will explore the genetic diversity and function of the Major Histocompatibility Complex (MHC) in order to test the Red Queen Hypothesis. The immune system is essential for combating pathogens and MHC proteins play an important role in the vertebrate immune system. Before we can test the Red Queen Hypothesis you need to know a little about the vertebrate immune system.

Diversity of Pathogens

Pathogens are any organism or agent that can produce disease. This definition is broad and encompasses many types of organisms. If you were asked to name a pathogen you would likely think of a bacteria like Streptococcus pneumonia (causes bacterial pneumonia) or Mycobacterium tuberculosis (causes tuberculosis). Or perhaps you would think of a virus like SARS-CoV-2 (the cause of COVID-19) or a retrovirus like Human Immunodeficiency Virus (HIV).

However, pathogen is a term that includes many other organisms and agents, such as:

• Parasitic worms like roundworm, tapeworm, and flatworm can cause diarrhea and nausea.
• Protozoa which are single-celled organisms that can cause diseases like malaria and sleeping sickness.
• Fungi like Candida albicans which causes thrush.
• Prions are misfolded proteins that can cause normal variants of the same protein to misfold. Prions are a cause of neurodegenerative diseases in humans and animals.

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The point of the information above is that the term pathogen includes a large variety of organisms and agents. For example, there are about 1,400 known species of human pathogens. An immune system is required to respond to this diverse set of invaders.

To respond to pathogens, vertebrates have an immune system with many specialized cells and molecules – this is amazing for our health, but challenging to learn! Our goal in this section is to gain a sufficient understanding of vertebrate immune systems in general, and specifically of MHC proteins, so we can understand how that connects to the Red Queen Hypothesis and mate choice. Here we go!

Non-Specific Immunity

The immune system is composed of two parts: “non-specific” and “specific” immunity. As you read, remember that these two parts of the immune system communicate and work together.

Non-specific immunity refers to the parts of the immune system that recognize a broad range of pathogens and have a rapid, immediate response. This response is always present, defends against all pathogens (rather than specific ones) and is the same response for all pathogens. All vertebrates are born with a functioning non-specific immune system.

The first step in the battle against pathogens is to keep pathogens out. Barrier defenses like skin, mucous membranes, and secretions both provide a barrier to entry and can destroy pathogens due to acidity or dryness (Figure 7.13).

If a pathogen makes its way through the barrier defenses, then it will encounter internal defenses. Phagocytic cells are a group of many types of cells capable of a process called phagocytosis, which causes pathogens to be engulfed by a phagocytic cell and degraded. Phagocytosis leads to the destruction of pathogens.

While there are several cells involved in the non-specific immune response, we will focus on one group, the antigen presenting cells (APC). A subset of phagocytic cells are also APC. These cells phagocytose a pathogen and break it down into smaller fragments called antigens. It is important to remember that each antigen is unique, because each pathogen is slightly different in its structure. As the name implies, APCs will display the antigen on their external cell surface. This presentation of antigens is the bridge between the non-specific immune response and the specific immune response. We will explore antigen presentation further in Section 7.7.

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Specific Immunity

Cells involved in non-specific immunity recognize all pathogens and respond to them the same way every time. In contrast, specific immunity recognizes unique pathogens and then must be trained to respond, with each exposure leading to a stronger and faster response.

So, how are the cells of the specific immune response trained? An APC that has phagocytosed a pathogen and presented its antigen (i.e. displayed the antigen on its external cell surface) will move to the nearest lymph node where they will encounter T cells (center of Figure 7.13). Humans have approximately 4×10¹¹ (one hundred billion) T cells in their body, but remember each T cell recognizes a specific antigen. Therefore, the APC must wait in the lymph nodes for the unique T cell that recognizes this antigen to come by. This is why the specific immune response is slower than the non-specific immune response.

Before we can describe the job of the T cell, we also need to know about B cells. Like T cells, B cells have proteins on their surface that are capable of binding to specific antigens. When a B cell recognizes an antigen, it is also capable of phagocytosis and presentation of the antigen, so it is also an APC.

Binding of a T cell to the antigen presented by an APC leads to activation of the T cell. Now that the T cell is active, it helps B cells mature. A mature B cell will undergo mitosis to make many more B cells all capable of recognizing the pathogen that is currently invading the body. One group of mature B cells will secrete antibodies. Recall the protein on the B cell’s surface capable of binding to specific pathogens…that is the antibody. When a B cell is mature it secretes antibodies which go out and bind to pathogens, marking them for destruction. It can take a few weeks for antibody levels to peak during the first exposure to a pathogen.

The other group of mature B cells become “memory B cells”. Memory B cells remain in the body for decades, monitoring for the presence of that same pathogen. If that pathogen were to appear again there would be many more B cells present allowing for a faster detection and stronger response. There are also memory T cells that remain, adding to the memory of the specific immune system.

NOTE: The information above is simplified and focused on the parts of the immune system relevant for our discussion. For a more complete description of the immune system, watch Introduction to the immune system (16:29), but be warned that it includes more than you need to know for this class.