Biology Biology Assignment

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BIO 331 Immunology Lecture
Name: Dr. William Carr
Example Final Assignment for Case 42 Celiac Disease
Part 1 – Clinical Case Summary (Word Count: 350):
In Case 42: Celiac Disease, a 12-month-old female, Irish-American infant presents to her
doctor with symptoms of weight loss, distended abdomen, and muscle wasting. Her doctor
conducted blood tests that found she had anemia, anti-endomysium IgA antibodies, and antitissue transglutaminase antibodies. Her doctor also performed upper GI endoscopy and biopsy,
which identified edema and small intestine villous atrophy with increased intraepithelial
lymphocytes (IELs). The key findings of anti-endomysium IgA antibodies, anti-tissue
transglutaminase antibodies, and small intestine villous atrophy with increased IELs were
consistent with a diagnosis of celiac disease. This disease is caused by both cell-mediated and
humoral immune responses by T and B cells of the adaptive immune system. In this disease CD4
T cells recognize gluten-derived gliadin peptides presented by antigen-presenting cells to initiate
inflammation in the gut mucosa. This inflammation damages healthy mucosa of the gut and limits
absorption of essential nutrients, which causes weight loss. To treat this disease she was given
nutritional counseling and a gluten-free diet, which effectively resolved her disease.
In this case, T cells as well as B cells are the key immune components. Both B cells and T
cells acquire antigen specificity through V(D)J recombination in the generation of their antigen
specific receptors. Normally B cells develop in bone marrow and undergo negative selection in
bone marrow to establish tolerance to prevent them from attacking healthy tissues. Normally T
cells mature in the thymus and undergo positive selection to enable recognition of MHC
molecules presenting antigenic peptides. In thymus, negative selection establishes central
tolerance so that mature T cells do not attack healthy tissues. To identify extracellular pathogens,
B cells directly recognize antigens through their B-cell receptor (antibody). To identify
extracellular pathogens, CD4 T cells recognize MHC class II-peptide complexes presented by
antigen presenting cells, such as macrophages or dendritic cells. To identify intracellular
pathogens, CD8 T cells recognize MHC class I-peptide complexes presented by antigen presenting
cells. In health, these cells are prevented from damaging healthy gut mucosa by Treg cells,
tolerogenic macrophages, and tolerogenic dendritic cells, which secrete cytokines, such as IL-10,
that suppress pro-inflammatory immune responses.
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Part 2 – Multiple choice questions with feedback:
1. Normally, induction of IgA antibodies is beneficial. Which of the following best explains
why it is detrimental in this case?
a) IgA antibodies with anti-endomysium and anti-tissue transglutaminase specificities
cause autoimmune disease, which is detrimental.
Feedback – You are correct! Antibodies that react to healthy tissues by definition cause
autoimmune disease.
b) IgA antibody responses do not provide systemic protection against pathogens.
Feedback – Your answer is incorrect. While it is correct that IgA antibodies are expressed
at mucosal surfaces and do not provide systemic protection, this does not explain why
these antibodies are detrimental in this case. This response option does not take into
account the specificities of the IgA antibodies.
c) IgA antibody responses interfere with IgG antibody responses.
Feedback – You are incorrect. IgA and IgG antibodies can have the same specificity for
antigen, but they have different functions. Thus, IgA responses would not interfere with
IgG responses.
d) IgA antibodies and gliadin peptides derived from gluten form immune complexes that
impair organ function.
Feedback – You are incorrect. While IgA antibodies may form immune complexes with
gliadin peptides, there is no clinical evidence that these immune complexes impaired
organ function, such as impairing kidney function.
e) IgA antibody production in the submucosa damages tissues.
Feedback – You are incorrect. Normally IgA antibodies are produced in the submucosa,
but they do not cause disease. The location of where the IgA antibodies is produced is not
relevant to the occurrence of disease in this case.
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2. Activation of which of the following immune cells would likely improve clinical
outcomes in celiac disease?
a) CD8 T cells
Feedback – You are incorrect. In this case, CD8 T cells contribute to damaging health cells
in the small intestine. Thus, activating these cells would make the disease worse.
b) Intestinal macrophages
Feedback – You are incorrect. In this case, disease is caused by immune cells attacking
healthy tissues. By activating intestinal macrophages in the absence of any pathogens,
these immune cells are likely to damage healthy tissues and make inflammation of the
small intestine worse.
c) CD4 TH1 cells
Feedback – You are incorrect. CD4 TH1 T cells are pro-inflammatory T cells that promote
TH1 inflammatory responses, such as promoting cell-killing and interferon-gamma
cytokine production. Thus, activating these cells would make inflammation of the small
intestine worse in this case.
d) CD4 Treg cells
Feedback – You are correct! The function of regulatory T cells is to maintain peripheral
tolerance. Thus, activation of these cells would reduce inflammation in the small intestine,
which is causing disease in this case.
e) NK cells
Feedback – Your answer is incorrect. NK cells are part of the innate immune response. In
this case, there are no pathogens present, so activating NK cells would likely cause them
to attack healthy cells and make this disease worse.
Part 3 – Short Answer Questions Answer Key:
1. Question 1 – Given the high prevalence of celiac disease and the difficulty in maintaining a
gluten-free diet, are there any new therapies on the horizon for this condition?
A new therapy that shows much promise as an alternative to a gluten-free diet is ALV003. ALV003
is an orally administered mixture of two recombinant gluten-specific proteases. These proteases
breakdown gluten and protect against gluten-induced mucosal damage.
2. Question 2 – How is a food determined to be gluten free?
Foods that are labeled gluten-free per the Food and Drug Administration (FDA) contain less than
20 ppm (parts per million) of gluten. This is the lowest level that can be detected in foods using
modern analytical tools.
oats with other gluten-containing grains at the processing plant. Therefore, the introduction of
oats into a gluten-free diet is tolerable.
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Part 4 – Self-Reflection Essay (minimum 300 words):
An example of this essay is not provided here, because each student will provide answers
based on their own personal experience. This essay should be written using complete sentences
in a narrative paragraph form (minimum 300 words), and address the following 8 questions: (i)
why did you choose the case that you selected, (ii) how did having choice of clinical cases impact
your motivation, (iii) how did working in a group affect your ability to complete this work, (iv)
how did you respond to feedback – what was helpful and what was not helpful, (v) what was your
greatest challenge in this process, (vi) what did you learn about yourself that you did not expect,
(vii) based on what you know now, what would you have done differently, and (viii) also speculate
what this experience might mean for how you approach interpreting clinical data and scientific
texts/ communications going forward.