Immunology Flashcards
(37 cards)
What type of lymphocytes are involved in central and peripheral tolerance?
- Central: developing lymphocytes
- Peripheral: mature lymphocytes
Where do both T and B cells develop?
- T cells: thymus
- B cells: bone marrow
What is involved in T-cell central tolerance?
autoimmune regulator protein (AIRE): thymic cells express tissue-restricted antigen to educate T cells on periphery
What happens if there is a lack of AIRE? How does this relate to IDDM?
- lack of AIRE = no negative selection (autoimmunity)
- IDDM -> insulin gene not expressed on AIRE -> autoimmunity to insulin
What population of cells handles T-cell peripheral tolerance? What do they secrete?
Tregs - secrete IL-10 and TGF-B to inhibit T cell and B cell inflammatory response
What 3 things are upregulated on Tregs that aren’t on any other cell type?
- Foxp3: allows them to express CTLA-4 and CD25
- CD25: high affinity IL-2 receptor
- CTLA-4: high affinity for B7 -> beats out CD28 and T cells become anergic
What does the loss of Tregs/foxp3 lead to?
widespread autoimmunity
What is involved in B cell central tolerance that is unique to B cells?
receptor editing: expression of a new light chain region
What is the inhibitory receptor used in peripheral B tolerance?
Fc receptor on the surface of B cells -> binds to antibodies and shuts down internal B cell signaling
What is functional inactivation of B cells?
peripheral tolerance where B cell is activated but signaling not done properly - no involvement of complement or TLR -> anergy
Name 7 trigger/risk factors for NIDDM
- microbiome: delivery; Abx
- diet
- energy expenditure
- early life: placental function, postnatal growth
- sleep debt
- chronic inflammation
- genetics: coupled w/ environment
What type of immune cells does lean adipose tissue largely contain?
contains Tregs, M2 macrophages (anti-inflammatory) and Th2 cells (suppressive)
Explain how necrosis can occur in adipocytes? What does this lead to?
adipose tissue is highly vascularized -> fat cells get larger (obesity) -> constrict vasculature -> necrosis -> inflammation
What is there in influx of when adipose tissue become inflamed?
M1 macrophages and acute phase cytokines (IL-1, IL-6, and TNF)
What does the inflammatory reaction in adipose tissue lead to (3)?
- acute phase protein production from liver
- hypothalamus inflammation
- TNF -> vascular permeability -> leukocyte migration to area of inflammation
What affect does IL-6 have on each of the following: liver, skeletal muscle, adipose tissue, and GI tract?
- liver: acute phase proteins and insulin resistance
- skeletal muscle: increase GLUT4 translocation and lipolysis
- adipose: increase lipolysis
- GI tract: increase GLP-1 in intestine and pancreas
What receptor is found on adipocytes and what can this lead to?
TLR4 found on adipocytes -> binds to palmitate (long chain FFA) -> pro-inflammatory response
What types of immune cell changes occur in adipose tissues in obesity?
- increase in M1 macrophages and CD8 T cells
- Decrease in M2 macrophages and Tregs
What type of hypersensitivity is IDDM?
Type IV hypersensitivity - T cell mediated
What other disease are IDDM pts likely to develop?
25% of developing Celiac disease
Which HLA class II alleles are found in 90% of people w/ IDDM?
DQ2/DQ8
Which HLA class II alleles are most common in children dx before age 5 w/ IDDM?
DR3/DR4
Which HLA class II alleles are considered protective against IDDM?
DR2/DR6
Which class of variable number tandem repeats (VNTR) increases the risk of IDDM?
Class I
