hypersensitivity is the phenomenon where the immune system's cells overreact against non-pathogenic antigen. there are four classifications based on the mechanism of the immune response. type I hypersensitivity is the allergic response; involves a class switch from IgM to IgE and a Th2 based response. an example is an allergy to corn: corn particles are ingested by dendritic cells and macrophages in the intestinal lymph tissue and presented to a CD4 cell. if co-stimulatory molecules are expressed, and the cytokines IL-10 and IL-15 are secreted, the CD4 cell differentiates into a Th2 cell, secreting IL-4,5,13. IL-4 causes a class switch from IgM to IgE, which causes binds to mast cells and causes degranulation and also secretion of TNF-alpha (TNF-alpha damages intestinal epithelium, contributing to leaky gut, potentially worsening the allergic response).
type II hypersensitivity is characterized by release of antibodies specific for molecules on cell surface. an example is the hypersensitivity to penicillin, which can occur when penicillin binds to a glycosylated protein on red blood cells. antibodies specific for the penicillin then bind to the redbloodcell/penicillin and are subsequently attacked by macrophages, resulting in hemolytic anemia (note that this is not an autoimmune response because the macrophages are targeting the penicillin primarily).
type III hypersensitivity is characterized by antibodies that are specific for soluble proteins- generally only occurs with high levels of soluble proteins. this often results in the formation of large antibody-soluble antigen complexes which can grow to block vessels or tubules. when this occurs macrophages and neutrophils are recruit to phagocytose the complexes and often damage the peripheral tissue by way of ROS production.
type IV hypersensitivity is a t-cell mediated response against antigen. the example given to us is celiac disease, which is a hypersensitivity to a peptide in wheat, gliadin. wheat is transported in from the lumen of the gut into the peyer's patches by microfold cells, where it can be ingested by macrophages and dendritic cell. these cells present the wheat peptide in an MHC to a CD4 t cell; if there is no co-stimulatory molecule expressed as well, this leads to a state of anergy and peripheral tolerance in the t cell. if there is co-stimulatory molecule expression (note that the increased microflora that enters the intestinal layers due to leaky gut can increase the likelihood of expression of co-stimulatory molecules) the CD4 t cell will be differentiated into a Th3 cell, which will proliferate and secrete TGF beta, resulting in a state of tolerance.
questions
different hypersensitivity mechanisms...
1. what is type I hypersensitivity characterized by?
2. what is type II hypersensitivity characterized by?
3. what is type III hypersensitivity characterized by?
4. what is type IV hypersensitivity characterized by?
5. what does an immune response dominated by Th2 result in? Th1?
6. what type of hypersensitivity is a penicillin hypersensitivity? describe the immune response.
7. why is a penicillin hypersensitivity not considered an autoimmune disease considering that red blood cells die in the process?
8. describe a typical type III hypersensitivity immune response.
9. describe a typical type IV hypersensitivity immune response.
celiac disease...
10. why is celiac disease not technically an allergic response?
11. what is the antigen in celiac disease?
12. describe the class switching mechanism in celiac disease.
13. what are microfold cells?
14. describe the activation of CD4 t cells in celiac disease.
15. when is a Th2 response employed in celiac's disease as opposed to a Th3 response?
other food allergies...
16. what are some characteristics of foods that commonly yield allergies?
17. describe how an allergic reaction to corn can lead to leaky gut.
18. what are some foods that typically create an allergic response?
answers
1. allergies, class switch to IgE
2. IgG against a surface protein
3. IgG against a soluble protein
4. t-cell mediated response
5. Th2 dominance is an allergic response, Th1 dominance is autoimmune disease.
6. type II hypersensitivity. glycosylated protein on RBC binds to penicillin, which is then opsinized by antibody, priming it for destruction by macrophages- resulting in hemolytic anemia.
7. because the immune response is against the penicillin, not the RBC’s- they are just a casualty.
8. antibody is released in response to soluble antigen; large antibody/antigen complexes form that can clog vessels. macrophages and neutrophils phagocytose complexes and create ROS which can damage the periphery.
9. the tuberculosis test is a typical type IV hypersensitivity response. purified protein derivative (PPD) is injected into the body- macrophages or dendritic cells ingest, carry to lymph nodes, and activate a Th1 response- T cells return to the infection site.
10. because there is no IgE class switch or a Th2 response- this is a Th1 response mediated by CD4 and CD8.
11. gliadin- resembles transglutaminase.
12. instead of being caused by a cytokine, it is caused by a the CD40/CD40L on B cell.
13. cells on the intestinal epithelium that transports whole antigen to the peyer’s patches.
14. dendritic cells or macrophages will ingest the wheat and produce one of two responses in T cells: if there is no co-stimulatory molecule, the T cell will go into the anergic state. if there is a co-stimulatory molecule (can be due to microflora entering from leaky gut caused by wheat), this causes IL-10 secretion and differentiation into Th3 cells, which secrete TGF beta, producing tolerance.
15. when IL-10 is secreted alongside IL-15.
16. high concentrations of hard to digest proteins, they make it far down the GI tract before being absorbed.
17. corn particles are ingested by macrophages in the peyer’s patches, and presented alongside CD86 (which is expressed for unknown reasons) to a CD4 t cell. the t cell differentiates into a Th2 cell by way of IL-10 and IL-15 cytokines, and secretes IL-4,5, and 13. IL-4 causes a class switch to IgE, which causes mast cells to degranulate and secrete TNF-alpha, which breaks down gut barrier and causes leaky gut.
18. dairy, soy, wheat, shellfish, nuts, corn, eggs, potatoes.
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