Question

In chapter 20 we covered the immune system, both the innate and adaptive. Choose a pathogen and describe how the body will use both innate and adaptive means to combat this pathogen. Get creative with this, there are so many different viruses, bacteria, and parasites that can make us sick!

Make sure you mention the disease/parasite/ailment that is caused by the pathogen, what the body does to protect itself innately, and how the body adapts to this.

Answer 1

The immune system rests on two major pillars: the innate, general defense and the adaptive, specialized defense. Both systems work closely together and take on different tasks.Both parts of the immune system work on different levels: Firstly, there are special defense cells in the different tissues that are directly involved in eliminating pathogens (germs). These cells belong to the so-called cellular defense.

Secondly, both the innate and the adaptive immune system also need several soluble substances found in blood and other body fluids. These are mainly proteins like enzymes, antibodies and short amino acid chains. These substances belong to the humoral defense (from the Latin humor meaning: “fluid”). So both parts of the immune system – the innate and the adaptive – use cellular and humoral defense strategies.

Innate immune system: Fast and broadly effective

The strength of the innate, general defense is to be able to take action very quickly. It makes sure, for example that bacteria that have entered the skin through a small wound are detected and partly destroyed on the spot within a few hours. As the innate immune response is not specialized for specific pathogens, it does not need a long start-up phase. Because of this broad effect, it is only capable to a certain degree of stopping germs from entering and spreading in the body.

The innate defense consists of several elements:

• The skin and all mucous membranes in the body openings, which form external barriers

• Different defense cells from the white blood cell group (leukocytes)

• Various substances in the blood and in body fluids

Protection from the outside: Skin and mucous membranes

All external and internal surfaces of the human body are a key element of the innate immune system. The closed surface of the skin and of all mucous membranes already forms a mechanical barrier for pathogens, which prevents them from entering. Additionally, chemical substances like acid, enzymes or mucus prevent the bacteria or viruses from gaining a foothold. Movements created, for example, by hair-like structures in the bronchi (cilia) or by bowel muscles stop germs from settling in the body. Tear fluid, sweat, or urine rinsing the urinary organs all have a similar effect.

Protection from the inside: Defense cells and proteins

If, despite all obstacles, pathogens make it past the skin or mucous membranes and enter the body, the innate system’s second line of defense comes into action. Inflammatory cells move to the site of infection, or defense cells that are already there are activated. Soluble protein substances of the complement system (see below) are activated, too, and help to defend the body. This leads to an inflammatory reaction where blood circulation is increased and the affected area becomes swollen and hot. Sometimes there is also a fever.

If bacteria or viruses manage to enter the body they can be eliminated directly on the spot by scavenger cells or phagocytes (from the Greek phagein, meaning: “to eat”). Two types of defense cells are the most effective ones: macrophages, which are found in the tissue, and neutrophil granulocytes, which are in the blood and tissue. These cells enclose the pathogens and digest them in their interior. Scavenger cells can work best if the pathogen has already been marked by antibodies or proteins of the complement system. This makes the pathogen more “palatable” for the scavenger cells.

So at this point, antibodies of the adaptive immune system support the innate defense. Vice versa, the scavenger cells can help the adaptive immune system by taking up and digesting the marked pathogens very quickly.

Complement system: Proteins in a chain reaction

Soluble substances support the defense cells of the innate immune system. A total of nine different enzymes activate one another in a process similar to a chain reaction: one enzyme of the first stage alerts several enzymes of the second stage, each of which again activates several enzymes of the third stage, and so on. This process quickly makes the defense reaction a lot stronger, because the production of these protein substances increases in such large jumps (exponentially).

The tasks of these enzymes:

• They mark pathogens, making them more attractive for scavenger cells.

• They attract other immune cells from the blood.

• They dissolve the cell walls of bacteria, so that they lose fluid and minerals and die.

• They fight viruses directly by destroying the virus envelopes, or indirectly by destroying cells infected by viruses.

Natural killer cells: Searching for changed body cells

The natural killer cells are the third important part of the innate immune system. They specialize in identifying cells that are infected by a virus or that have become tumorous. They do this by looking for changes in cell surfaces. If natural killer cells find cells with a changed surface, they dissolve them using cell poisons, also called cytotoxins.

The adaptive immune system: Precision and a long memory

If the body’s first line of defense – the innate immune system – is unsuccessful in destroying the pathogens, after about four to seven days the specific adaptive immune response sets in. This means that the adaptive defense takes longer, but it targets the pathogen more accurately. Another advantage: It can remember the aggressor and acts specifically against certain antigens. If there is new contact with an antigen that is already known, the defense response can then be quicker. This way the defense responses of the adaptive immune system are more efficient and faster than those of the innate defense, if the antigen is already known.

The adaptive immune system can remember the antigens because it produces memory cells. This is also the reason why there are some illnesses you can only get once in your life, because afterwards your body becomes “immune.” While after first contact with the pathogen it takes several days for the immune system to respond, a second infection often has no consequences, or at least the symptoms are weaker.

The adaptive immune system has several parts that react in different ways, depending on the place in the body where the pathogen is. Antibodies are made available for germs outside the cells (in the blood and in body fluids). To eliminate pathogens that are inside the tissue, a cell-mediated immune response is necessary.

These parts of the adaptive defense include:

• T lymphocytes

• B lymphocytes

• antibodies as soluble proteins in the blood

• cytokines in the blood and tissue as hormone-like messenger substances

T lymphocytes

In the adaptive immune system, T lymphocytes (T cells) are responsible for the special defense in the tissue, which is carried out by cells. They recognize infected cells and are responsible for their destruction and elimination from the body.

T lymphocytes belong to the group of white blood cells and, in adults, are produced in the bone marrow. In the thymus gland, they mature into cells that are capable of recognizing self from non-self cells. T cells have characteristic structures on their surfaces that pathogens can bind to – similar to a lock that a specific key fits to.

A pathogen that exactly fits a T cell stimulates this T cell to multiply quickly and to develop into specialized T cells. At the same time, the great number of newly produced T cells triggers other defense reactions. This leads to the pathogens being destroyed and eliminated from the body.

During the course of a defense reaction, T lymphocytes develop into specialized cells. These include:

• T helper cells

• T killer cells or cytotoxic T cells

• memory T cells

• regulatory T cells

B lymphocytes

B lymphocytes are an important pillar of the adaptive defense: They produce antibodies, which are in the blood as soluble proteins and are specialized for exactly one pathogen.

The cells of the adaptive immune systems interact either directly by binding to the surface of different defense cells or they use soluble messenger substances like the cytokines. These messenger substances are mostly proteins and are produced by different cells in the organism.

T cells

Once formed in the bone marrow, T progenitor cells migrate to the thymus (hence the name “T cell”) to mature and become T cells. While in the thymus, the developing T cells start to express T cell receptors (TCRs) and other receptors called CD4 and CD8 receptors. All T cells express T cell receptors, and either CD4 or CD8, not both. So, some T cells will express CD4, and others will express CD8.

Unlike antibodies, which can bind to antigens directly, T cell receptors can only recognize antigens that are bound to certain receptor molecules, called Major Histocompatibility Complex class 1 (MHCI) and class 2 (MHCII). These MHC molecules are membrane-bound surface receptors on antigen-presenting cells, like dendritic cells and macrophages. CD4 and CD8 play a role in T cell recognition and activation by binding to either MHCI or MHCII.

Macrophage binding to T cell

T cell receptors have to undergo a process called rearrangement, causing the nearly limitless recombination of a gene that expresses T cell receptors. The process of rearrangement allows for a lot of binding diversity. This diversity could potentially lead to accidental attacks against self cells and molecules because some rearrangement configurations can accidentally mimic a person’s self molecules and proteins. Mature T cells should recognize only foreign antigens combined with self-MHC molecules in order to mount an appropriate immune response.

T cell positive selection and negative selection

In order to make sure T cells will perform properly once they have matured and have been released from the thymus, they undergo two selection processes:

1. Positive selection ensures MHC restriction by testing the ability of MHCI and MHCII to distinguish between self and nonself proteins. In order to pass the positive selection process, cells must be capable of binding only self-MHC molecules. If these cells bind nonself molecules instead of self-MHC molecules, they fail the positive selection process and are eliminated by apoptosis.
2. Negative selection tests for self tolerance. Negative selection tests the binding capabilities of CD4 and CD8 specifically. The ideal example of self tolerance is when a T cell will only bind to self-MHC molecules presenting a foreign antigen. If a T cell binds, via CD4 or CD8, a self-MHC molecule that isn’t presenting an antigen, or a self-MHC molecule that presenting a self-antigen, it will fail negative selection and be eliminated by apoptosis.

These two selection processes are put into place to protect your own cells and tissues against your own immune response. Without these selection processes, autoimmune diseases would be much more common.

T cell positive selection and negative selection process

After positive and negative selection, we are left with three types of mature T cells: Helper T cells (T\text{}_{H}H​start subscript, H, end subscript cells), Cytotoxic T cells (T\text{}_{C}C​start subscript, C, end subscript cells), and T regulatory cells (T\text{}_{reg}reg​start subscript, r, e, g, end subscript cells).

• Helper T cells express CD4, and help with the activation of T\text{}_{C}C​start subscript, C, end subscriptcells, B cells, and other immune cells.
• Cytotoxic T cells express CD8, and are responsible for removing pathogens and infected host cells.
• T regulatory cells express CD4 and another receptor, called CD25. T regulatory cells help distinguish between self and nonself molecules, and by doing so, reduce the risk of autoimmune diseases.

A good example of immunological memory is shown in vaccinations. A vaccination against a virus can be made using either active, but weakened or attenuated virus, or using specific parts of the virus that are not active. Both attenuated whole virus and virus particles cannot actually cause an active infection. Instead, they mimic the presence of an active virus in order to cause an immune response, even though there are no real threats present. By getting a vaccination, you are exposing your body to the antigen required to produce antibodies specific to that virus, and acquire a memory of the virus, without experiencing illness.

Some breakdowns in the immunological memory system can lead to autoimmune diseases. Molecular mimicry of a self‐antigen by an infectious pathogen, such as bacteria and viruses, may trigger autoimmune disease due to a cross-reactive immune response against the infection. One example of an organism that uses molecular mimicry to hide from immunological defenses is Streptococcus infection.