The evidence points to a huge problem.
An interesting study has uncovered some immune system-derived factors that predict the development of severe disease in humans.
Made With Paper
This is not a kidney, but a lymph node, where B cells differentiate into antibody-secreting plasma cells and memory cells which play a big role in our body’s humoral immune response. In the humoral immune response, B cells secrete antibodies which neutralise pathogens (esp. viruses) and prevent them from binding to host cells during a prolonged infection.
One of the multitude of reasons your biology allowed you to live past your second or third birthday, drawn in adorable fashion.
Louis Pasteur- father of immunology. Also discovered attenuated vaccines.
A basic overview
- Immunology is the study of molecules, cell, organs, and systems responsible for the recognition and disposal of foreign (non-self) material.
- The immune system has five basic characteristics:
- Natural selection does not have a goal.
- Your evolutionary lineage has been evolving for the same amount of time as the lineage of the bacteria in your intestines.
- You are more complex than the bacterium, but you are not more highly evolved.
- The fact that many bacterial species have existed largely unchanged for millions of years means that they’re probably better adapted to their environment than you are to yours.
Perhaps highly-derived in some cases?
Well, it’s been quite a while since my last post…again. Between class and lab I’m pretty swamped these days. In addition to that, I do put a good bit of work into these posts and I tend to think quality is more important than quantity. The outcome of which is that I don’t post when I don’t have time to write a good post.
That all aside, I thought I’d explain the big-picture rationale for one of my projects. Translation from basic research to clinical application (often referred to as ‘bench to bedside’ is a major goal of the field of biomedical research right now, and for good reason. The potential implications of my project for patient care are, like many others, several steps removed from the conclusions I hope to draw. Nonetheless, I think it’s an important aspect of the immune system to understand and one that could lead to changes for the better in therapeutic and preventative medicine.
An immune cell’s ability to move into, out of, and through tissues of the body is essential to its proper functioning. I’m specifically interested in how T cells accomplish this, but the same principles can be applied to any other immune cell subset. CD4+ T cells, for example, carry out a number of roles in a variety of tissues depending on the type of immune reaction underway. In the case of intracellular pathogens like Leishmania major, Toxoplasma gondii or Francisella tularensis, CD4+ T cells need to make direct contact with infected cells wherever they may be. These pathogens multiply inside host immune cells (often macrophages) where they can evade the mechanisms that phagocytes usually use to dispose of such invaders. These phagocytes can only do so much on their own. Without T cells stimulation, specially evolved pathogens can circumvent the limited mechanisms available to a phagocyte on its own. Once a T cells arrives on the scene, it can stimulate the phagocyte to produce more powerful chemicals and enzymes that help to destroy the pathogen. A failure in the ability of T cells to respond appropriately to this sort of infection can lead to serious or even lethal complications, as in the case of tuberculosis or visceral leishmaniasis.
Go home, T cell. You are drunk.
One critical step in this process is the migration of the T cells from its steady-state location to the site of infection somewhere in the periphery. This process usually involves many phases that must be executed properly to ensure the efficient clearance of infection. A naïve T cell under normal conditions can be found circulating through the peripheral lymphoid organs (like the spleen and lymph nodes) searching for antigen presenting cells that are displaying its particular antigen. Once it finds and APC with its antigen in the presence of inflammatory mediators, the T cells integrates various signals from the environment and matures into an effector cell that is ready to carry out its function. Next, the T cells needs to leave the lymph node, a process that requires certain surface molecules that it acquired during maturation, and migrate through the lymphatic ducts and into the circulatory system. Once in circulation, special surface molecules (again, imparted by the maturation process in the lymph node) direct the T cell to the tissue where it is needed. The T cells must then push its way out of the blood vessel and through whatever interstitium lies between it and the site of infection. This could mean traversing the alveoli of the lung, the dermis of the skin, or lamina propria of the intestine. In any case, the T cell needs a specific set of surface molecules that will allow it to migrate efficiently in each of these unique situations.
Many of these processes remain poorly understood. But, thanks to new technology such as two-photon microscopy, we are able to observe T cell movement in real-time and begin to tease apart the particulars of how they are carried out and the implications for disease.
Things have been really busy lately; between starting up new projects in the lab and a quick vacation to California. That, coupled with a lack of inspiration, has resulted in a significant lag in my posting here. So, in order to get things moving once again, I decided to tackle a topic I’m a little weak on myself: B cells! And, of course, one can’t discuss B cells without first having a solid understanding of antibodies.
Antibodies are Y-shaped molecules that are either secreted by B cells or expressed on the B cell surface in a form called a B cell receptor (BCR). Antibodies arise from a process known as ‘VDJ recombination’ in which the heavy chain and light chain which compose the antibody are modified at the genetic level. When everything goes right, the finished product is a BCR with an entirely unique specificity to some foreign molecule and no reactivity to any self-generated molecules. When a B cell is activated in a process often, but not necessarily, involving T cells, the B cell integrates signals from multiple sources to determine which antibody class to manufacture. When a B cell switches the class of its antibody (a process known as ‘class switching’) the antigen specificity is unaltered. The only change occurs in the end of the antibody that interacts with other elements of the immune system.
Antibodies play many important roles in the immune system and their function is dependent on their particular class. The different classes of antibodies, or ‘immunoglobulins’ (IgA, IgD, IgE, IgG, and IgM), each serve a unique function in the process of defense against pathogens. IgE, for example, is most well known for being the culprit behind some common types of allergic responses. This, however, is not IgE’s true evolutionary purpose. IgE has evolved as a mechanism of defense against large, extracellular parasites (Platyhelminthe worms and nematodes like Trichinella). IgE functions by being secreted into mucosal tissues (such as in the digestive and respiratory tracts) and attaching to special receptors on the surface of immune cells like mast cells. These receptors bind to the Fc (fragment of crystallization) portion of the antibody, opposite the Fab (fragment of antigen binding) so that the antigen-specific surface is pointed out and away from the cell. When the IgE binds its specific ligand, the mast cell is signaled to release granules containing, among other things, histamine. Histamine is the chemical known to be involved in the vasodilation that results in itching, sneezing, and watery eyes associated with some allergies. However, when this reaction occurs in defense against a parasitic worm, it can result in the pathogen’s destruction or ejection from the body.
Other antibody types, such as IgG2a and IgG3, serve to activate a class of molecule call ‘compliment’ that can result in the destruction of pathogenic bacteria. Still others can cover viruses, preventing their entry into cells. Some can also cover bacteria or cancer cells, signaling macrophages to ingest them.
Antibodies are an elegant and amazing adaptation that is essential to the proper functioning of the immune system (as evidenced by individuals lacking them: http://en.wikipedia.org/wiki/X-linked_agammaglobulinemia)