Self study: autoimmunity of the GI tract week 1 Flashcards

1
Q

autoimmunity

What cells does the adaptive immune response consist of? What are their functions?

A

Autoimmunity is an assault of healthy tissue and cells by the adaptive immune response.

Adaptive immune response consists of B- and T-cells. These lymphocytes orchestrate and ultimately mediate the destruction and clearance of pathogens and transformed cells from the body. They also leave an “imprint” in the immune response so that future response to the pathogen of transformed cells will be rapid and heightened.

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2
Q

What do B-cells recognize?

What do T-cell recognize?

A

Normally B-cells recognize proteins, lipids, complex carbohydrate structures and nucleic acids of pathogens, which differ from selfmacromolecules. These macromolecules are known as “antigens”.

T-cells only recognize “foreign” peptides presented by cell surface proteins known as major histocompatibility complex molecules (MHC). Free peptides do not trigger a T-cell response. Peptides presented by MHC are recognized by T-cells.

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3
Q

What are the antigen receptors present on B-cells called?

What happens when these antigen receptors are activated?

A

The antigen receptors present on B-cells are called immunoglobulin (Ig). When Igs are engaged they activate the B-cell to differentiate into plasma cells. Plasma cells secrete Ig known as antibodies. The antibodies bind antigen and are able to facilitate biological responses leading to clearance of the pathogen and its products.

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4
Q

What is the name of the antigen receptor present on T-cells?

What triggers activation of this receptor and what is the response of T-cells to this activation?

A

The antigen receptor present on T-cells is called a T-cell receptor (TCR). TCRs recognize peptides presented by MHC on all cells, which are infected with a pathogens or antigen presenting cells which process pathogen macromolecules. Either way the peptide presented by the MHC will trigger TCR to activate the cell. This process leads to proliferation and production of soluble factors known as “cytokines” to trigger activation, differentiation and expansion of reactive cells within the immune response.

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5
Q

How does the body protect itself from immune responses to “self” as far as B and T cells are concerned?

What cells are responsible for the autoimmune response?

A

Although the immune response is very specific and responsive to pathogens, it is capable of responding to “self”. To avoid this the body has developed several layers of protection. One of the major ways to avoid self is to eliminate self reactive lymphocytes. During development , if TCR engage self-peptides they are programmed to die. If B-cells respond to self-macromolecules they also are programmed to die. However, lymphocytes are responsive to self escape elimination. These cells are responsible for autoimmune response. Typically 5% of all Americans suffer some form of autoimmune disease.

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6
Q

T or F: Rarely, autoimmune responses are due to changes in events leading to programmed cell death. In vast majority of people with autoimmune responses the failure to control anti-self is due to ability to eliminate self-reactive cells. This is because we have developed specialized cells capable of recognizing a vast majority of pathogens and their products some of which overlap with self antigens.

A

True.

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7
Q

What 3 conditions are essential for developing autoimmunity?

A

1) MHC molecules present specific “self” peptides to T cells. These species of MHC molecules are inherited and have a different capacity to bind peptides. Type I diabetes, which is present in 2% of the population, is increased to 20% among people who have two alleles of MHC molecules.
2) The presence of a specific TCR can increase the likelihood that a peptide presented by a specific allele of MHC will trigger a response. Similarly, Ig on B-cells must be able to be formed to recognize a specific self-antigen. The ability to generate a specific TCR or Ig that recognize self-antigen is a chance event. In fact, identical twins may not have the same TCRs or Ig on the their T-cells or B-cells, respectively.
3) The third event is environmental. This is known as microbial mimicry. This is the case where a microbe product resembles a self macromolecule. A good example is Streptococcal Group M antigen which is a common protein among Streptococcus that causes strep throat. This antigen is common among tissue that makes up the mitral valve of the heart. Thus, cross reactive Ig and TCR that respond the Group M antigen leads to a damaged heart valve during rheumatic fever.

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8
Q

What are the 2 types of gastritis? What are they caused by?

A

Type A is autoimmune-mediated
Type-B is Helicobacter pylori infection-mediated

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9
Q

What is Type A gastritis also known as? What is the mechanism of this autoimmune disease?

A

Type A is also know as pernicious anemia (PA). Typically it is due to malabsorption of vitamin B12. Over 90% of patients who have PA produce antibody to a cell antigen against the gastric parietal cells. About 70% of patients produce antibody to intrinsic factor (IF). IF binds to vitamin B12 in the stomach. It is produced by gastric parietal cells. IF-B12 complex then binds receptors within the small intestine. Two types of autoantibodies bind to IF. One type of antibody binds to the B12 binding site. The other antibody binds IF outside of binding site and prevents it from binding to receptors on the small intestine. Also, auto-antibody to parietal cells leads to elimination of IF as well since antibody bound cells are destroyed.

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10
Q

What is celiac disease?

What are characteristics of the disease?

A

Celiac disease is a relatively common small intestine disorder resulting from immune-based hypersensitive to ingested gluten (storage protein of wheat). One characteristic of celiac disease is loss of normal villi and increase in the number of lymphocytes present in the epithelial layer. The lamina propria shows a marked increase in plasma cells, lymphocytes and granulocytes.

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11
Q

What alleles are celiac disease strongly associated with? What do they code for? What is their function? How do they play a role in the disease?

What role do T-cells play? What symptoms/processes do their actions lead to?

A

Strongly associated with HLADQ2 and HLA-DQ8 alleles. These are MHC class II molecules which present peptides to CD4+ Tcells (also know as T helper cells). MHC class II molecules present a unique 33 amino acid gluten peptide. The gluten peptide undergoes deamination in the small intestine by an enzyme known as transglutaminase. The deamination of glutamine residues to glutamic acid results in a negative charge, which increase binding of peptide to HLA-DQ2 and HLA-DQ8. The deaminated gluten peptide is cleaved into small subunits in antigen presenting cells and presented to T-cells via MHC class I molecules.

These activated CD4+ T-cells produce interferon gamma. This cytokine provokes a strong inflammatory response, which leads to mucosal damage in particular damage occurs to villi. Typically the damaged intestinal tissue leads to increased diarrhea and malabsorption of nutrients and vitamins.

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12
Q

What are 2 types of inflammatory bowel disease (IBD)?

A

ulcerative colitis (UC)

crohn’s disease (CD)

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13
Q

Where in the GI tract are UC and CD manifested? What are common features of IBD?

A

They are both chronic inflammatory diseases. UC is limited to the colon while CD occurs in any part of the GI tract (most common in the ileocecal region). One of the common features of IBD is loss of goblet cells and formation of crypt abscesses. Infiltration of leucocytes into the GI tract is commonly associated with IBD.

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14
Q

T or F: Genetic factors are involved in IBD.

A

True. Genetic factors are involved in IBD. UC is most common in people with HLA-DR2 (allele of MHC class II molecules). CD is complex and usually is associated with regions of the chromosomes encoding nitric oxide dismutase 2 and interferon-gamma. Both are factors associated with inflammation.

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15
Q

What are possible possible causes of IBD?

A

The pathogenesis of IBD remains a mystery. Factors such as disruption of epithelial cell integrity and loss of regulatory cell and cytokines may initiate the diseases. Moreover, environmental factors trigger a loss of tolerance to intestinal flora in genetically susceptible individuals.

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16
Q

What cytokine is implicated in Crohn’s disease? How is this taken advantage of in treatment of CD?

A

Tumor necrosis factor alpha, which is a cytokine produced during inflammation by macrophages and natural killer cells exacerbates Crohn’s Disease. Management of TNF-D with specific inhibitors (e.g., infliximab) leads to remission.