T cell Development Defintions

Anergy: Unresponsiveness to antigenic stimulus

 The CD4+ T cell received only the TCR engagement signal and none other, therefore anergy  was experienced.  

 

Notch: A surface receptor that when bound is cleaved to release a transcriptional regulator that regulates cell fate decisions. Notch activation is required for T cell development and determines whether a lymphocyte precursor becomes a B vs. T cell.

 When Notch 1+ is added to stromal cells in an assay system, this induces the development of T cells rather than B cells.

 

Death by Neglect: Apoptosis of developing T cells (Typically CD4+ & CD8+ T cells) that results when they do not receive TCR signals of adequate affinity.

 

Most T cells (about 90%) undergo death by neglect in the Thymus because their receptors do not specifically recognize self MHC molecules.

Rheumatoid Arthritis Investigation

Autoimmune diseases are very interesting to study because of the mechanisms that underlie their existence and how the body mistakenly begins to fight itself. I chose to investigate the autoimmune disease Rheumatoid arthritis because my father has been diagnosed with Arthritis and I was interested in becoming knowledgeable of what could possibly be going on the inside of my father’s body.

            Rheumatoid Arthritis (RA) is an autoimmune disease in which our immune system attacks its own joints, resulting in inflammation on the inside (synovium) and bone deterioration. As the synovium thickens this tends to cause swelling and pain which usually leads to a loss of mobility. The joints at risk for RA include the hands, feet, wrists, elbows, knees and ankles. Interestingly this disease usually affects joints symmetrically, meaning that if one elbow becomes impaired it is very likely that the other elbow will be affected as well. The etiology of RA is currently uncertain but research has been able to detect many of the important immune components that trigger the inflammation and bone resorption.

            Some of the chemical mediators that trigger inflammation in RA include kinins and vasoactive amines. Kinins are a group of polypeptides that have the ability to stimulate smooth muscle, increase vascular permeability, induce pain and possibly promote leukotaxis. Histamine, a vasoactive amine is believed to have a major role in the initiation of the inflammatory response in RA. It also encourages vasodilation and vascular permeability. Lysosomes which are involved in the digestive and lytic process of cells have been suggested to release their enzymes directly into cell cytoplasm or surrounding tissue in RA, which injures the tissue and triggers the inflammation response. If this action is prolonged it results in the continuous production of autoantibodies because of the antigenic stimulation by degraded host tissues.

            Patients with RA have an increased number of T cells, which is explained by the role they play in triggering osteoclastogenesis. Osteoclstogenesis is the development of osteoclasts, which are bone cells that are specialized to reabsorb calcified tissue. This is the reason why patients with rheumatoid arthritis experience the pain they do, because with time their bones start to become fragile due to the action of these overstimulated osteoclasts. T cells express RANKL which is a member of the TNF family of cytokines. RANKL induces osteocalstogensis from monocytes or macrophages.  

 

Wilder, Ronald L. "Immunopathogenesis of Rheumatoid Arthritis." Clinical Immunology Newsletter 6.1 (1985): 1-5. Web

Panayi, G. S. "Developments in the Immunology of Rheumatoid Arthritis, a Personal Perspective." Rheumatology 50.5 (2011): 815-17. Web.

MHC & Ag presentation Encounter:

In class we have been studying the major histocompatibility complex along with antigen presentation. There are two pathways in which antigen is processed and presented to T cells depending on whether the peptide is associated with MHC class- I or MHC class-II. The Endogenous pathway is the pathway taken by peptides generated within the cell (MHC I). The Exogenous pathway is the pathway taken by peptides taken up from the extracellular environment by endocytosis (MHC II).

This past weekend our acrobatic team was away at Andrews University in Michigan for our annual Acrofest. During our nine hour bus ride there one of my teammates threw up in the bus on his way to the trashcan. Our coach made a stop to attempt to clean the area since we still had a couple hours till arriving at our destination. However, germs are hard to kill especially in an enclosed environment filled with people such as our bus. When we arrived at acrofest three other teammates progressively got sick and started to throw up as well. In the midst of this happening I couldn’t help but think about immunology and what was happening on the inside of my teammates as they were trying to fight off this virus or stomach flu. To this day we aren’t sure what exactly plagued our team.

What I am sure about is that these antigen peptides from the throw up were spreading and as they started to inhabit my teammates their immune systems were at work. These peptides were coming from the outside, therefore their system was fighting through the exogenous pathway. In the exogenous pathway the antigen is engulfed into endocytic compartments where they are degraded by acidic pH-dependent endosomal and lysosomal enzymes. These throw up peptides were then able to associate with MHC class –II and the MHC-peptide complexes were then transported to the cell membrane in preparation for antigen presentation to CD4+ T helper cells. Thankfully these teammates were able to recuperate before our performance Saturday night, meaning that their antigen presentation was successful and their immune system was actively at work in fighting off this stomach illness.

Antibody genes/MHC Reflection

Immunology class is one of my favorite classes because the immune system is fascinating to me. In class we have been discussing antibodies and how the genes are organized and expressed in the genome. I remember before I took the class Dr. V asked me if I had taken genetics and my response was no, well this is the section where it would be helpful to have a bit of background knowledge. In class I do my best to take notes and listen attentively, however I find myself not understanding some of the concepts and having to read outside of class more. I am a visual and kinesthetic learner so when we did the in class activity where we lined up with the Ig germ line segments it helped me enormously. I believe we should do more activities like this to make sure we are grasping the concept and making connections in our brains. Great pictures would also be helpful. Up to this far I have enjoyed all the topics, but this chapter in particular I’m not particularly a fan of and I believe it’s because I’m having a hard time understanding. The overall concept of the genetics of antibodies is very interesting and I know I will appreciate it more as I begin to grasp the concepts. As soon as we switched to the next chapter dealing with MHC my interest was sparked again because of the relevance there is when dealing with transplants and autoimmune diseases. Two of the most important things I have learned in this section has been that the variable and constant regions are encoded in two separate segments. The light chain is composed of a V and J region, while the heavy chain is composed of V, D, and J regions. Another very important concept that I learned was that RSS sequences ensure that each type of segment is included in the recombined variable region gene. RSS is composed of a heptamer, a 23 bp or 12 bp region and a nonamer. An extremely important concept is that each 12bp (one turn) must be joined to a 23 bp (two turn) as you go downstream the germ line. Both the studies of antibody genes and MHC are crucial to the field I plan to purse in the future. As a future health care provider I may be faced with having to understand antibodies in depth when dealing with diseases to suggest a treatment plan or I might need to be knowledgeable about MHC if I am going to participate in a transplant surgery.