Question

Purpose: To strengthen and demonstrate your knowledge of the Immune and Lymphatic System and its systemic relationship in the body. The ability to apply this content and think systemically with physiology processes will benefit you as a healthcare student and practitioner.

Criteria for Success: To be successful you will make sure you complete diagrams as instructed in the tasks, including proper values (if required) on the x & y-axis as well as labeling those. You also need to make sure to list or provide explanation where necessary or where it is asked in the tasks. A successful submission would be very clear and easy to read and it would be easy to identify antibodies, immune responses, etc. For submission, you can submit them as a pdf or image from a phone if you are drawing these at home. I also suggest looking at the homework you have completed and the provided examples to help you in completing these tasks.

Case Studies Tasks:

Daniel: Susan and Joe had a wonderful little boy named Daniel, bu he had been having an awful lot of bacterial infections and he was barely a year old. It seemed that the antibiotics cleared up one bacterial respiratory infection only to have another follow shortly. The scary thing was that Daniel had just fought of a case of pneumonia caused
by Pneumocystis carnii, a fungal infection that was usually found in people with HIV. Waiting for the test
results of an HIV test for their little boy was one of the worst experiences ever. Thank goodness it came back negative.
However, it seemed that their troubles were just beginning. After this last lung infection, the fungal one, and
a negative HIV test, their doctor had ordered a number of other blood tests, including a genetic test that
Susan didn’t fully understand. Apparently the doctor was worried about Daniel’s immune system functions.
Susan had also met with a genetic counselor who collected a family history of any immune disorders. The
details were vague, but Susan’s mother, Helen, knew that one of her three brothers had died young from an
unexplained lung infection. Unfortunately, Grandma Ruth had passed away a few years ago, leaving them
with numerous unanswered questions. Susan and Joe had an appointment with their doctor that afternoon to go over the results. When they arrived Dr. Dresdner led them into an office where Ms. Henchey, the genetic counselor, waited. This can’t be good, thought Susan. The doctor began by explaining that they had analyzed Daniel’s blood and found that while he had normal levels of B cells and T cells, his antibody levels were anything but normal. The levels of
IgG, IgA, and IgE were very low, almost undetectable, and Daniel had abnormally high levels of IgM and IgD.
It appears that his immune system failed to undergo immunoglobulin isotype switching due to a CD40 ligand mutation in Daniel's DNA.

1. Diagram an antibody response graph for a normal 1st and 2nd exposure with the antibodies correctly labeled for each exposure. Then diagram what Daniel's graph would look like.
2. Diagram and/or explain why IgG is low and what CD40's role is? Why is a mutation in that gene a problem?

Charlotte: A 60-year-old woman was fit and well until late in the summer she was out tending to her lovely tulip garden when she was stung on the back of her right hand by a pesky wasp. This was nothing new, unfortunately as she had been stung a couple times in the last two weeks. With in minutes after this sting Charlotte fell to the ground and looked as though she was becoming pale/grayish and was gasping for air. After five minutes it was getting worse, but likely a neighbor doctor rushed over and administered an epinephrine shot, which provided support until the ambulance could arrive.

1. Which antibodies and cells are are involved in this allergic reaction and how does it lead to anaphylaxis? Why didn't this happen on the first stings?
2. How does anaphylaxis impact the body and how did the epinephrine help?

Jessalyn: Jessalyn regularly goes in for blood transfusions. Jessalyn's blood type is O+. Normally her blood transfusions go well and her nurse, Traci, does a great job of double checking the blood type she is receiving. This time Traci is out of town and she gets a nurse who was able to skate through school doing the bare minimum and doesn't really care that much about his job. He doesn't double check the blood type for her transfusion and . . .

1. The blood type was incorrect. Diagram and/or explain what happened.
2. Which blood types could Jessalyn receive, why?

Answer 1

1. Daniel's case: HIGM syndrome

This is the representation of normal individual which shows that the IgG production is far greater than the IgM while IgM is the first antibody produced during the primary response.

In Daniel's case this is the representation of the antibody production. During the primary response the IgM concentration is large while the secondary response consists of decrease in the IgM as well as IgG level because the memory cells for IgM are not produced while th production of IgG ceases due to the inability of class switching.

Daniel suffers from a disease known as Hyper IgM syndrome (HIGM). People with this syndrome are susceptible to recurring and severe infections. This disease is caused due to the inability of class switching from the IgM to the other type i.e IgG, IgA, IgE. Therefore, it is charactrized with low levels of IgG antibody and an elevated levels of IgM. For class switching of the antibody production the B cells need to interact with the T-lymphocytes. A genetic defect can affect this interaction.

Cause: The main cause for the occurence of  HIGM syndrome is a genetic defect which is caused by the mutation in the gene expressing for a protein known as CD40 ligand (located on the surface of atctivated T-lymphocytes). This CD40 ligand binds with CD40 protein on the B-lymphocytes for the productionn of the different antibodies.So due to the mutation a defected or deficient CD40 ligand is unable to interact with the B lymphocyte and is unable to instruct the B cells to switch their production from IgM to other type. Moreover, the defective CD40 ligand can affect the cellular immunity which makes the individual susceptible to infections.

HGIM syndrome is a X linked recessive disorder as the CD40 ligand is expressed by a gene on X-chromosome. Therefore, this disease is only inherited by boys.

2. Charlotte's case: Allergic reaction

The allergic reaction in the body are caused due to the production of IgE antibodies.These IgE produced bind to a specific receptor present on the surface of mast cells and basophils and produce an acute inflamatory response.The foreign agent that triggers the allergic reaction binds to the IgE immunoglobulin which in turn activates the receptor FcεRI  on mast cells and basophils.The activation of the receptor causes the release of histamine whivh produces inflammation and causes anaphylaxis by subsequently increasing  the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression.

During the first encounter with the bee the body produces a primary response against it which involves recognization of the antigen and production of antibody against it. This the reason why the first encounter does not lead to the allergic reaction and anaphylaxis which eventually occurs during the secondary encounter.

Epinephrine works on the alpha 1 receptors and reverse the symptoms of anaphylaxis. It induces the vascular smooth muscle constriction,pupillary dilator muscle contraction, and intestinal sphincter muscle contraction.

3. Jessalyn case: Incorrect blood transfusion

The transfusion of a mismatched typr of blood can cause ABO incompatibility reaction in the body which can be fatal and result in the hemolysis (lysis of the RBCs), blood clotting and shutting off the blood supply to vital organs.

The hemolysis due to ABO incompatibility is caused due to the activation of complement system. The receiver cells (O blood type) contains no antigens on the surface of the RBC while it contains all the antibodies in the serum. The incorrect transfusion of the blood which may contain antigens triggers the the production of antibodies IgM against it. The bound IgM molecule is then recognized by serum complement C1 complex which interacts with it to activate the classical pathway resulting in complement deposition on the donor cell and eventual clearance or lysis of host RBCs by the membrane attack complex (MAC).

Jessalyn should only receive the blood from either O+ or O- individual because then no antibodies will be formed against them as they do not contain any antigen.