Immunity

Third and final post for this week's Topic Quiz!

Today we're going to touch on immunity. Emphasis on "touch on," because immunology is a whole field of its own.

Types of Immunity

There are two main types of immunity: innate and acquired. Innate immunity is basically all of the non-specific defenses that our body can use immediately. Examples of this include anatomical barriers such as skin, as well as non-specific molecules such as lysozymes and defensins. Acquired immunity, on the other hand, takes longer to kick in, but it can target and kill specific pathogens. There are two subtypes of acquired immunity: active acquired immunity, in which you build up antibodies to an antigen that you have been exposed to, and passive acquired immunity, in which you just steal antibodies from someone else (e.g. mothers pass antibodies to their babies, antiserum contains antibodies against specific antigens).

Antibodies

First up, we're going to talk about a very important aspect of acquired immunity: antibodies! Antibodies are produced by B-lymphocytes, which mature in the bone marrow. (An easy way to remember this is "B" for "bone.") Antibodies can hang out in the membrane of B-lymphocytes, serving as B-cell receptors (BCR). When B-cells are activated, they can differentiate into plasma cells, which continue to produce antibodies, or memory cells, which help the body "remember" the antigen for future reference.

Antibodies, as you're probably well aware, are Y-shaped structures. They are made up of four chains: two identical heavy chains and two identical light chains. The top "arms" of the Y are known as the F_ab end, which can bind to antigens. The bottom part of the Y is the F_c region, which can bind to F_c receptors on other cells.

Not all antibodies are created equal. There are five main types of antibodies:

• IgG- The most common type of antibody. They are able to cross the placenta.
• IgA- Antibodies present in secretions such as milk, saliva and bile. Generally seen as a dimer (i.e. they look like 2 antibodies stuck together).
• IgE- Antibodies prominent in allergic responses.
• IgM- Antibodies involved in the primary response to an antigen. Generally seen as a pentamer (look like 5 antibodies stuck together).
• IgD- function not quite clear right now.

Just a quick note on IgM and the primary response- during your first exposure to an antigen, it'll actually be IgM that kicks in first (well, before other antibodies that is). This is then followed by IgG. During subsequent exposures to the same antigen, IgG produces the main response.

Antibodies have many important functions. Firstly, as explained in my previous post, they can act as opsonins, which helps other cells to phagocytose the bad stuff. They can cause agglutination (clumping) of antigens and neutralise toxins, preventing them from entering cells. They can also play roles in activation of immune cells and complement. Antibodies are said to have a humoral response- that is, they act by travelling through blood.

T-cells

In contrast to the humoral response exerted by antibodies, T-cells exert a cell-mediated response. They mature in the thymus gland ("T" for "thymus!") and have T-cell receptors (TCR) in their membranes. T-cells are kinda fussy- most of them only interact with antigens that are presented to them on MHC proteins. So let's have a look at what MHC proteins are!

MHC proteins, or Major Histocompatibility Complex proteins, are membrane proteins present on all nucleated cells. They are also known as HLA, or Human Leukocyte Antigen. As well as presenting antigens, they are also important "self" markers: a large number of alleles code for MHC molecules so the chances of two people having the same MHC molecules is pretty much zero (unless they're identical twins).

There are two main classes of MHC molecules. MHC class I is present on all nucleated cells, and binds peptides from invading pathogens. This allows cytotoxic T-cells (yeah, there's different kinds of T-cells- I'll get to them in a bit) to kill the infected cell. MHC class II is only present on specialised antigen-presenting cells, such as macrophages and dendritic cells. MHC class II interacts with helper T-cells, which in turn activate B-cells and cytotoxic T-cells.

Now I'll finally get to the types of T-cells!  There are two main types: helper T-cells with CD4 markers (T_h) and cytotoxic T-cells with CD8 markers (T_c). Cytotoxic T-cells kill stuff whereas helper T-cells just help coordinate everything via cytokines. That's not to say they're not important: helper T-cells actually outnumber cytotoxic T-cells 2:1 because they're pretty damn important. Another type of T-cell that you should know about are suppressor T-cells, which turn off activated cytotoxic T-cells and thus prevent the immune response from going overboard.

NK cells

Another important type of lymphocyte to know about is the NK cell. NK (Natural Killer) cells are part of the innate immune system because they act quickly and non-specifically. They can bind to a range of microbial peptides, and are pretty good at killing cancer cells and virus-infected cells. One of their weapons of choice is interferon, which as I mentioned in my previous post, can interfere with viral replication and prepare cells for viral attacks.

Blood Groups

Unfortunately the immune system doesn't always produce desirable responses. One example of this is agglutination, or clumping, if you give someone the wrong type of blood in a transfusion.

As you probably know, people can be one of four blood types: A, B, AB and O. These letters refer to the antigens present on the surface of red blood cells. Even though red blood cells (a.k.a. erythrocytes) are non-nucleated and thus lack MHC antigens, they do have other glycoproteins on their cell surface. People with type A blood have A antigen, people with type B blood have B antigen, AB has both antigens, and O has neither. People also have antibodies against the antigens that they don't have- type A has anti-B antibodies, type B has anti-A antibodies, and so on. This is why type O (which has no antigens) is considered to be the "universal donor," whereas type AB is the "universal recipient."

Hypersensitivity (a.k.a. Allergies)

Another example of the immune response going awry is the allergic response. An allergy is basically just the immune system responding to something innocuous, like a peanut. There are four main types of hypersensitivity, but for now I'm just going to talk about Type I and Type IV. (These are pretty much the immediate and non-immediate drug reactions that I spoke about in a post for PHAR2210.) One thing that all types of hypersensitivity have in common, however, is that sensitisation (prior exposure to that antigen) is required first.

Type I hypersensitivity, or immediate hypersensitivity, occurs within minutes of exposure. Essentially, a sensitised person will develop IgE against the antigen, which sit pretty on mast cells. When the person is re-exposed, the antigen binds to the IgE, causing mast cells to degranulate and inflammation to occur.

Type IV hypersensitivity, or delayed hypersensitivity, takes a few more days to develop. This is mediated by T-lymphocytes. An example of a stimulus that can cause delayed hypersensitivity is poison ivy.

Fortunately, there are things that can be done to help allergy sufferers. Some people can get allergy shots, which are injections of small amounts of the antigen. This stimulates production of IgG. Upon subsequent exposure to antigen, this IgG will bind to the antigen, preventing its binding to IgE and degranulation of mast cells. This IgG doesn't stick around forever, unfortunately, so allergy sufferers do need to go back for allergy shots every once in a while.

And I'm done typing about the topics for the first test! Yay!