End of the Semester Reflection

As we come to the close of another semester I can’t help but to look back through the weeks of taking this course and feeling accomplished. This immunology course has broadened my horizons on a branch of biology that is key to working in the healthcare field. I believe that everything that happens under the sun, happens for a reason. My academic journey has humbled me extensively by constantly reminded me that God is ultimately in control. I am a senior who is having to do an extra semester, outside of the normal 4 year curriculum. I have wrestled with God when it comes to my academic journey and my future and there are many questions I still don’t have answers to. I never saw myself having to do an extra semester because my goal from the beginning of my college journey was to finish on time and graduate as young as possible. However, my journey is not everyone else’s and in the midst of wresting with God, He convicted me in switching my major from Health Science to Biology. This switch set me back a bit but I was determined to embark this harder road with the goal of being a better candidate in the future when applying to graduate school. However, making this decision gave me the opportunity to take this course, which caught my attention since last year when some of my colleagues were taking it. Two of the most important concepts I have learned about include the MHC complex and antigen presentation along with the functions of antibodies. Taking biochemistry simultaneously with this class has enriched my learning tremendously. In biochemistry we recently had an entire chapter that gave an overview of the immune system and the major roles of B cells, T cells and immunoglobulins. It was amazing to see how much background knowledge I obtained in the field of immunology as I explained the content to my study group colleagues who have not taken the course. Overall, I am thankful for the knowledge I have gained which has allowed me to have a new perspective when dealing with diseases, colds and allergies. I now can't help but to think about the functions of the immune system when I encounter scenarios such as someone having a cold or listening to a  conversation that ties to the immune system. I am in awe when I see how God has created an “army” within us whose sole purpose is to protect us.  

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.

 

Organization of Lymphocyte Receptor Genes Defintions

Germ-line theory: Suggests that genetic information for each antibody is encoded, in its entirety, within the germ-line genome.

After revaluations and calculations the germ-line theory was not accurate because there simply was not enough DNA to fit the size of antibody repertoire.  

 

Recombination Signal Sequences (RSS): Specific DNA sequence motifs that ensure one of each type of segment (V & J for the light chain OR V, D & J for the heavy chain) is included in the recombined variable region gene.

The RSS for the V region must be 3’, while the RSS for the J region must be 5’ in order to be compatible for joining.

Terminal deoxynucleotidyl Transferase (TdT): Enzyme responsible for the generation of additional diversity in the CDR3 region of the antibody heavy chain

TdT, RAG1 and RAG2 are the three proteins implicated in V(D)J recombination that are unique to lymphocytes.

Specific Antibody Deficiency (SAD) Investigation

           In class we have been discussing the structure and function of the different classes of anitbodies we find in our immune system. Our body contains five classes on immunoglobulins which include IgA, IgG, IgD, IgE, and IgM. Out of these five IgG is the immunoglobulin who has the main role in protection against infections, as it protects us from bacteria and viruses. SAD is a disorder in which a person has normal levels of all immunoglobulins except IgG. Due to the fact that IgG having a main role in protecting against infection, it is common for patients with SAD to experience recurrent infections. Particularly it has been found that IgG acts against the sugar coat of illnesses such as Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza. This is because IgG produces molecules against the pathogens that cause upper and lower respiratory infections.

            However, as crucial as IgG is to our immune system, our bodies are equipped with other components that also help in fighting off infections such as T cells, complements proteins, other WBCs and IgA. This explains why some patients diagnosed with SAD rarely get sick. This means that their other components are working well together and compensating for the deficiency of IgG. In general, the infections suffered by patients with SAD are not as severe as those suffered by patients who have combined deficiencies of IgG, IgA and IgM. For example diseases such as X-linked Agammaglobulinemia (XLA) or Common Variable Immune Deficiency. Although, often patients with SAD will come to the physician’s office with a single severe pneumonia or other infection.

          Although recurrent infections in the ears, sinuses, bronchi or lungs is usually a pretty good indicator of SAD, to diagnose precisely diagnose one must measure the total amount of immunoglobulins. Treatment for SAD usually can be treated with antibiotics, unless the infection has taken a severe course. In this case Ig replacement therapy is considered. Children are more likely to outgrow SAD through close monitoring and immunizations such as pneumococcal vaccines. If diagnosed as a teenager or adult it is less likely that the deficiency will be resolved on its own. In both scenarios close monitoring of the Ig levels is crucial.

 

 

 

"Specific Antibody Deficiency." Immune Deficiency Foundation. N.p., 2013.

        Web. 19 Oct. 2016. <http://primaryimmune.org/about-primary-

         immunodeficiencies/specific-disease-types/specific-antibody-         deficiency/>.                                                  

Post Exam 1 Reflection

My immunology learning has expanded more and more as the semester goes by both inside and outside of the classroom. In class lectures I am enriched with a lot of content and information as I do my best to keep up with the professor by taking notes and looking at the slides. Taking notes is definitely a method that works for me, because the act of writing the most important portion of what was said helps me make connections in my brain that are more likely to stay. Even if the professor is talking really fast and I feel as though I will not be able to keep up with my notes I still am convinced my “chicken scratch” is better than nothing. Another learning technique that I have found to be helpful outside of the classroom has been to make 3x5 color-coded notecards based on the slides and my notes. I used this notecards not only to study the material but also to make connections by grouping notecards in a kinetic manner. For this last exam that we had I made a large amount of notecards which was time consuming, but definitely worth it at the end because as I was answering the questions on the test I felt confident in knowing the material. Another study habit that helped me was encountering the material in different settings. For example, over the weekend I attempted to explain the core concepts of immunology to my mother in the most simplified way I could (in Spanish) so that she could understand. This method forced my mind to work extra hard in making connections both with the content and then translating them into Spanish. Surely the concepts I explained to her have been ingrained in my memory. I love immunology because it is a class that is extremely relevant to my future as I aspire to become a health professional. This class is surely preparing me for graduate school where I am sure to encounter the material again. Even more importantly it is preparing me to be able to diagnose my patients and educate them on how a particular disease is affecting their body, down to the cells and their mechanisms. I believe the two most important things I have learned in class thus far is the interaction between MHC class 1 and 2 and how the body uses these cell surface proteins to recognize self from non-self. The second most important thing I’ve learned is the process of inflammation and what is happening internally on the cellular level when the tissue is damaged.

Innate Immunity Definitions

 

1. Pathogen-associated molecular patterns (PAMPs): Conserved motifs, usually present many copies on the surface of a bacterium, fungal cell, parasite, or virus particle.

“Scavenger receptors recognize PAMPs such as LPS, lipoteichoic acid (LTA) or β-glucans and trigger phagocytosis.”

 

 

2. Opsonization: Deposition of opsonins on an antigen, thereby promoting a stable adhesive contact with an appropriate phagocytic cell.

 “Antibodies and complement components aid in opsonization by coating  a dangerous MRSA pathogen, making it "tasty” for phagocytic cells.

3. Toll-like receptors (TLRs): A family of cell-surface receptors found in invertebrates and vertebrates that recognize conserved molecules from many pathogens.

“Unique to among TLRs, TLR4 has been found to move from the plasma membrane where it binds to PAMPs and also in endosomes and lysosomes where it recognizes degradation of endocytosed pathogens.”  

Crohn's Disease Investigation

In class we have been covering the different cells involved in the innate response along with the mechanisms that allow it to work as our first line of defense. The innate response is able to do this because the innate response works in minutes/hours verses days. Innate immunity is not highly specific when it comes to killing pathogens instead it kills any pathogen and/or dead/damaged cells through phagocytosis. Phagocytic cells include monocytes, macrophages, neutrophils and NK cells. It is during the innate response that inflammation is triggered.
Usually immunological diseases take place in the adaptive response but a few disease arise when the innate response is not functioning correctly. One of these examples is Crohn’s disease.

Crohn’s disease is an inflammatory bowel disease (IBD) in which the end of the ilieum and the beginning of the colon are affected. We have harmless bacteria that lives in our guts that aid us in digestion. In a person with Crohn’s disease the innate system confuses this harmless bacteria for harmful pathogens and therefore initiates a response. This response causes inflammation in the intestines, which is the main characteristic of Crohn’s disease. The amount of neutrophils that are called to the site of infection in a patient with Crohn’s disease is diminished, which is also associated with the lower production of interlukin-8 and interlukin-1β. When the intestines are attacked in this way some intestinal content is removed the mucosal barrier is breached which aids to the inflammation. These patients have a weak innate immune system

 
Works Cited:
"Crohn's & Colitis." CCFA: What Is Crohn's Disease. N.p., n.d. Web. 30 Sept. 2016.

"Immunology of Crohn's Disease." Ann NY Acad Sci Annals of the New York Academy of Sciences 1079.1 Immunology of (2006): n. pag. Web.

Reflection Post

Immunology is one of those subjects that sparks a natural interest in me. When choosing classes for this semester I intentionally chose this course with the hope of learning so much more of the about the immune system. The concept of the human body fighting off diseases with mechanisms that operate without our consent is amazing to me and intrigues me. I believe this course is not only relatable but necessary for my future career goals. As a future health care provider being knowledgeable about the immune system will equip me for research and allow me to think critically when dealing with my patients. I must be able to teach my patients about the immune response and all the different diseases that are caused by a weakened immune system. In the healthcare setting I will be exposed to environments that contain many different pathogens and need to be aware of the potential risks that are associated with such pathogens for my own health. In class we have already had many interesting side discussions over real life scenarios where immunology is able to explain the causes. When I sit in these discussions and actively participate I start to feel like a diagnostic doctor trying to put the pieces together like a puzzle. I have found myself much more interested in regular conversations that involve the immune system, for example this past weekend I was visiting my boyfriend’s family and his friend started a conversation about her husband having an immune disorder in which his body could not make efficient CD4’s, immediately I looked over and had a light bulb turn on in my brain. She was talking about how he has to be careful because small infections can be magnified in his body. I thought to myself “those infections are called opportunistic infections” I listened actively and felt amazing for understanding what they were talking about. This course has actually helped me with Biochemistry as well, especially while we were talking about the antibodies used with the ELISA technique and how this technique successfully diagnoses diseases such as HIV because these antibodies detect specific proteins. I believe I am a hands on learner and like to learn by applying the material to real life situations. I know I have learned the material when I am able to explain it detailed to somebody else. I am excited to continue to learn about immunology and be blown away.  

Blood Work Encounter

I am happy to be part of the immunology class this fall because of the relevance I find in this subject pertaining to my future goals in the medical field. Just the name of the class sparks an interest in me because I know it deals to how our body fights pathogens that can be harmful and cause diseases. I found myself engaged from day one and continue to do so in class especially when we break into real life scenarios where we talk about the immune system in a very real and vivid way. On one occasion we broke out to talk about blood work labs and what the values represent which is where I made the connection to my encounter. At my job I handle patient blood work labs and scan them into our electronic system. When linking them into their electronic chart I have the option to pick an appropriate title for the document, unknowingly I would choose the title CBC W/ Auto Differential. After the discussion in class I learned that the auto differential is specifically talking about the different white blood cells and their relative percentages in the blood. Sure enough after learning this I noticed that majority of the blood work labs from places like Labcorp and Quest diagnostics precisely had all the percentages for all the different white blood cells. I was picking the correct title all along, but it felt great to know for a fact that I was correct in picking so because I had learned what auto differential meant. Now when I handle the labs I can’t help but to analyze them and look at the different white blood cells, thinking in my head of all their functions and what high or low percentages of them reveal. I feel so smart looking at these labs and understanding beyond the numbers. I feel like I’m getting a glimpse of the patient’s immunological state even if I am merely scanning the reports into the system. It has lightened up my once dull scanning routine and has added some immunological flavor to it. This experience excites me for the future and reminds me that one day I will be the one in the room with the patient consulting and explaining their labs to them.