https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h en-us 2022-04-20 14:13:03 UTC 2026-03-04 20:47:14 UTC hello@padlet.com cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150424737 B Cells 
> White blood cells that make antibodies

Antibodies 
> a blood protein produced in response to counteract a specific antigen

T Cells 
>  T cells circulate until they encounter a foreign antigen ]]> 2022-04-20 14:16:11 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150424737 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150425557 Paneth Cells
Paneth cells are located in the Villi and help break down fatty acids to absorb nutrients.
> They secrete antimicrobial peptides that kill pathogens in the membrane. 
> They have an important role in the immune system
> Interaction with the migration and replacement of villi 
> Stress, genetic predisposition make the membrane more permeable 

Innate Immunity 



]]> 2022-04-20 14:16:21 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150425557 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150430568 Autoinflammatory/Autoimmune disease in response to gluten ingestion in people who are genetically predisposed. ]]> 2022-04-20 14:19:16 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150430568 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150430947 There is inflammation, failure to thrive, and abdominal pain.
 Lowers life expectancy when detected after 18 years old 
Can progress into lymphoma & osteoporosis ]]> 2022-04-20 14:19:29 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150430947 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150436359 2022-04-20 14:22:43 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150436359 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150436999 HLA-DQ
> (HLA-)DQ2 or (HLA-)DQ8 alleles predispose a person to celiac disease
> Homozogous (two copies) DQ2 is possessed by most people with Celiac disease
> DQ8 still causes a risk for Celiac disease 
> Possible Exam Question: Which combination between DQ2 & DQ8 will result in Celiac disease? 





]]> 2022-04-20 14:23:06 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150436999 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150437375 IgA antibodies ]]> 2022-04-20 14:23:21 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150437375 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150438756 a) Sequence of Events ]]> 2022-04-20 14:24:12 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150438756 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150439116 2022-04-20 14:24:23 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150439116 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150439441

Gluten is broken down, releasing gliadin. 

Gliadin is first broken down by amylase in the mouth, once in the lumen it is broken down into smaller peptides that allow it to cross the lamina propia. 

• Passage to the lamina propia by compromised epithelial complex damaged by stress, bacterial toxin, or genetic predisposition. 

In the lamina propia, gliadin peptides are modified by transglutaminase 2 (TG2) which deamidates the glutamine residues into glutamic acid

• Increasing their affinity for HLA-DQ2 or HLA-DQ8 due to their more negative charge
• Tight junctions proteins are released 

Macrophages & dendritic cells absorb the deamidated molecule and present the gliadin peptide in the HLA. 

CD4+T-cells bind to the antigens presented by the dendritic cell. 

• TH1 reaction --> proliferation and production of cytokines (inflammation)
• TH2 reaction --> Activation and stimulates B cells to create antibodies IgA ( found in secretion), IgG (detoxifies, and recognition of antibodies complexes), IgM 
  • Different antibodies: one against gluten, one against TG2 
  • IgA attacks gliadin, TG2, and endomysial antibodies 
  • Activated B cells can differentiate into plasma cells that secrete antibodies against Gluten and TG2 

• Intraepithelial lymphocytes are found in the GI and reproductive tract
  • Contribute to the damage (villous atrophy) and are a marker for the disease 

]]> 2022-04-20 14:24:36 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150439441 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150439796 2022-04-20 14:24:48 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150439796 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150440629

https://pathology.jhu.edu/autoimmune/definitions 

 https://www-nature-com.eur.idm.oclc.org/articles/s41572-018-0054-z.pdf 

The Immune System Book

Article: “Triggers and drivers of autoimmunity: lessons from coeliac disease” by Ludvig M. Sollid and Bana Jabri 

Youtube: https://www.youtube.com/watch?v=Hxd0msD954I&ab_channel=ArmandoHasudungan 

Hypersensitivity: Microbiology: An Introduction - Chapter 19 (Pg 551-568)

]]> 2022-04-20 14:25:19 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150440629 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150448324 2022-04-20 14:29:46 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2150448324 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151818573 An antigenic response that results in undesirable effects in a damaging manner. 
> Caused by a particular antigen 
- Type I - response within 30 minutes 
> Allergies
- Type II - cytotoxic, response in 5 to 12 hours ]]> 2022-04-21 10:17:09 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151818573 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151819233 2022-04-21 10:17:58 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151819233 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151819344 2022-04-21 10:18:06 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151819344 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151819480 2022-04-21 10:18:17 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151819480 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151820312 2022-04-21 10:19:05 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151820312 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151820453 Autoimmune Disease: When the immune system acts in response to self-antigens and causes damage to one’s own organs

Autoimmunity might happen on a small scale, but once it crosses a threshold it turns into an autoimmune disease.

Celiac disease is not an autoimmune disease because it is not responding to an antigen coming from the body but one coming from gluten. 

Celiac Disease and Allergies use different T-Cells 
> Allergies - TH2 
> Celiac TH1 & TH17


]]> 2022-04-21 10:19:17 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151820453 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151842105 2022-04-21 10:41:37 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151842105 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151844045 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737358/pdf/0102-6720-abcd-28-03-00183.pdf]]> 2022-04-21 10:43:32 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151844045 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151845622 2022-04-21 10:44:56 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151845622 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151854965 Adaptive immune responses involved in coeliac disease. Owing to a high proline content, gluten is fairly resistant to proteolytic degradation by mammalian
and microbial digestive enzymes, which leads to the appearance of fairly long gliadin peptides, including the 33mer, in the small intestinal lumen. These peptides access
the lamina propria either actively through the transepithelial route or passively by paracellular flux caused by compromised epithelial barrier function. In the lamina propria, the immunogenic gliadin peptides are modified by transglutaminase 2 (TG2), which deamidates distinct glutamine residues into glutamic acid, increasing their affinity to human leukocyte antigen (HLA)-DQ2 or HLA-DQ8. These modified epitopes are taken up by antigen-presenting cells, including dendritic cells that present them to gluten-specific CD4+ T cells in the context of HLA-DQ2 or HLA-DQ8 molecules. Moreover, both gluten-specific and TG2-specific B cells have been suggested to act as antigen-presenting cells in coeliac disease. B cells recognize their antigens (gliadin peptides and TG2–gliadin complexes) via surface B cell receptors (BCRs), internalize them and present the processed gluten peptides to gluten-specific CD4+ cells. Upon the interaction of HLA-DQ2 or HLA-DQ8, gliadin peptides and distinct T cell receptors (TCRs), both the T cells and the B cells would be activated. Once activated, gluten- specific CD4+ T cells start secreting inflammatory cytokines, including IFNγ and IL-21, thereby creating an inflammatory milieu in the small intestinal lamina propria. Moreover, the activated B cells can differentiate into plasma cells that secrete antibodies against gluten and TG2. IEL, intraepithelial lymphocyte.]]> 2022-04-21 10:54:27 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151854965 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151870054 https://reader.elsevier.com/reader/sd/pii/S1074761304002390?token=9D201D7553CBC90D228F40E08F7D5A4979A430FDA0066DD71C9B0EA525034085054272A1F258F45436020445DCDEB418&originRegion=eu-west-1&originCreation=20220421111124]]> 2022-04-21 11:11:49 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151870054 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151878933 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003135/pdf/cmi201065a.pdf

]]> 2022-04-21 11:21:52 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151878933 siennaakkermans https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151881314 Infants exposed to dietary gluten early and in the presence of maternal IgA become tolerant of gluten, whereas infants exposed later and in the absence of maternal IgA are more likely to respond to gluten as though it were an infecting pathogen]]> 2022-04-21 11:24:29 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151881314 cristina3huezo https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151887301 Gluten-free diet 
> 30% of the patients do not respond to this treatment
--> Immunosuppressant to reduce inflammation
Take vitamin A, K, D, B12, Selenium 
Don't take supplements unless you need them ]]> 2022-04-21 11:29:38 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151887301 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151913269 Pathogenesis of celiac disease 
Ingestion
• Gluten-containing grains (wheat, barley, rye) are ingested
Entering digestive system
• The protein “gluten” enters into the digestive system
Intestinal proteases
Gluten is degraded in the gut lumen to resistant fragment (proline-rich 33-residue gliadin 
fragment).
• Gluten consists of proline- and glutamine-rich gliadin and glutenin subcomponents and the 
glutamine and proline-rich gluten composing proteins are partially hydrolyzed by proteases 
presented in the gastrointestinal. 
• The high content of proline in gluten proteins makes them resistant to degradation by 
intestinal proteases such that they can be found as long fragments (10–50 residues) in the gut 
lumen. 
• The proline-rich 33-residue gliadin fragment resists proteolysis, both by the extracellular 
digestive enzymes and the intracellular proteases of antigen processing
Substrate transglutaminase 
• These gluten fragments are good substrates for the enzyme transglutaminase, which converts 
certain glutamine residues to glutamate. 
• The proline-rich 33-residue gliadin fragment binds strongly to tissue transglutaminase. 
Deamination
• Resistant fragment enters gut tissue and is deaminated by transglutaminase.
• This process, known as deamidation, increases the ability of the gluten peptides to bind to 
HLA-DQ2 or HLA-DQ8 molecules.
• After transglutaminase has converted particular glutamine residues to glutamate, the 33-
residue fragment binds to HLA-DQ 
Activation inflammatory effector T cells
• By binding to HLA-DQ in different registers, the fragment presents distinctive epitopes to 
different clones of T cells; these have a synergistic effect in initiating the disease-causing 
immune response. 
• Naïve CD4 T cell responds to deaminated peptides presented by HLA (HLA-DQ, DQ2 or DQ8 
allotypes).
• CD4 TH1 cells that respond to gluten-derived peptides presented by DQ2 or DQ8 allotypes 
and secrete cytokines that orchestrate the inflammatory response.
Inflammatory response 
• Inflammatory effector T cells secrete cytokines that orchestrate the inflammatory response.
• Inflammatory effector T cells cause villous atrophy.

]]> 2022-04-21 11:54:46 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151913269 mmtzclaros1 https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151915586
The disease is characterized by the presence of specific serological antibodies, such as: anti-
tissue transglutaminase (tTG) IgA, anti-endomysium IgA (EMA) and anti-deamidated gliadin 
peptides IgG (DPG).
All patients with celiac disease make IgG or IgA autoantibodies specific for tissue 
transglutaminase. The presence of such antibodies is diagnostic for the disease, which is 
confirmed by biopsy of the small intestine. HLA-DQ typing can also be informative in 
diagnosis, because patients who lack DQ2 or DQ8 do not have celiac disease but have some 
other intestinal disorder. Most celiacs also make anti-gliadin antibodies. These antibodies are 
likely to be the products of B cells expressing surface immunoglobulins that bind and 
internalize complexes of transglutaminase and a gliadin fragment and then present modified 
gliadin fragments on HLA-DQ molecules to T cells.
Tissue transglutaminase (tTG) 
Generated gluten-derived peptides reach the lamina propria (mucosa) where they are 
modified by tTG enhancing their affinity to MHC II molecules, and thereby making them toxic 
and immunogenic in HLA-DQ2 or DQ8 containing patients. The repetitive presence of 
glutamine and proline residues determines the gluten-derived peptides as a preferred 
substrate for tTG. tTG-mediated modifications occur in two ways: deamidation (cleavage of 
the ε-amino group of a glutamine side chain) or more frequently transamidation (cross-
linking of a glutamine residue from the gliadin peptide to a lysine residue of tTG). Further 
peptides presentation by HLA-DQ2/DQ8 protein subunits in the surface of dendritic cells to 
gluten-specific T cells induces two levels of immune response: the innate response and the 
adaptive (T-helper cell mediated) response with the production of interferon-γ and IL-15. As 
a result, it causes immune-mediated enteropathy, intestinal inflammation, followed by the 
atrophy of villi, crypt hyperplasia and increased infiltration by intraepithelial lymphocytes. It 
also produces weight loss and chronic diarrhea. Although the causative agent is a dietary 
protein, the disease has marked autoimmune features, which are indicated by the presence 
of autoantibodies against tTG. Cross-linking between gliadin and tTG is covalent resulting in 
the formation of new epitopes, which trigger the primary immune response, and by which 
the autoantibodies against tTG are developed.]]> 2022-04-21 11:56:55 UTC https://padlet.com/cristina3huezo/ed33d2e4fv7tcl0h/wish/2151915586