Immunology (Exam I) Flashcards
Cells present in lean adipose tissue
Treg cells Th2 cells iNKT cells M2 macrophages Eosinophils
Cells present in obese adipose tissue
Th1 cells M1 macrophages CD8+ T cells B cells Dendritic cells Mast cells Neutrophils
Cytokines produced in lean adipose tissue
IL-4
IL-13
IL-10
Cytokines produced in obese adipose tissue
IL-1b
IL-6
TNF-a
Role of IL-6 in acute inflammatory response
Increase GLP-1 in pancreas
Increase GLP-1 in intestine
Increase lipolysis; increase AMPK in adipose tissue
Increase GLUT4 translocation; increase lipolysis in Muscle
Increase acute phase-protein response in liver
Increase insulin resistance in liver
How do FFAs induce an adipose inflammation
- Long chain FFA is a ligand for TLRs present in adipocytes
- Receptor/ligand binding leads to pro-inflammatory cytokine and chemokine production
- Recruitment and differentiation of M1 macrophages
- Inflammatory state leads to betta-cells dysfunction
T1D
True Autoimmunity
T-cell mediated (type IV hypersensitivity)
T-cell mediated destruction of beta-cells resulting in insulin resistance
Autoantibody production used as markers of beta-cell destruction
Strong HLA associations
Prone to ketoacidosis (unlike T2D)
Signs and symptoms of T1D
High blood sugar
Weight loss
Increased hunger
Increased thirst
Complications of T1D
Kidney failure
Cardiovascular disease
Diabetic retinopathy
Foot ulcers
Normal homeostatic conditions
Low glucose Low insulin Low FFA Low IL-1b High serum IL-1Ra
Genes involved in autoimmunity of T1D
HLA AIRE INS (insulin gene) CTLA-4 FAS PTPN22 CD25 (IL-2Ra)
Which chromosome is HLA II on?
Chromosome 6
What are the high risk HLA II alleles?
DQ2/DQ8
DR3/DR4
Haplotypes of HLA II found in 90% of individuals with D1D
DQ2/DQ8
Haplotypes of HLA II found in 50% of children diagnosed with T1D prior to age 5
DR3/DR4
HLA Class II that lacks _____of the beta chain are often found amongst individuals with T1D
Asp57
Hyplotype of HLA II that “protects” against T1D
DR2/DQ6
AIRE mutation
Defective expression and presentation of insulin in thymus to developing T cells
Diabetes
Adrenal
Parathyroid
In which chromosome is the Insulin gene located
Chromosome 11
How many classes of Insulin gene are there
Three:
Class I
Class II
Class III
Which class has relatively high risk for T1D
Class I
In which chromosome is the CTLA-4 gene located
Chromosome 2
On which cells is CTLA-4 normally expressed
Treg cells
Main function of CTLA-4
Inhibit immune response
Maintain tolerance
Mutation in FAS gene
Defective apoptosis of self-reactive B and T cells in periphery
Splenomegaly
Lymphadenopathy
Mutation in FOXP3
Deficiency of Tregs
IPEX- widespread autoimmunity
What does IPEX stand for?
Immune dysregulation
Polyendocrinopathy
Enteropathy
X-linked
Which gene contributing to autoimmune diseases is a tyrosine phosphatase?
PTPN22
Mutations in PTPN22 cause
RA
T1D
Autoimmune thyroid disease
Environmental risk factors for T1D
Decreased breastfeeding Increased Cow's milk exposure Decreased Vitamin D Childhood infections Chemicals Obesity Dietary factors
How do viruses lead to destruction of beta-cells?
Direct cytotoxicity
Molecular mimicry
What are the two main viruses implicated in T1D?
Mumps
Rubella
Which compounds from Streptomyces are cytotoxic to beta-cells?
Streptozocin
Bafilomycin A1
Classic Th1 response cytokines
IL-2
IL-12
INF-g
Which T cells produce IL-4?
Th2
What is the main role of IL-4 in T1D autoimmunity?
Activates B cells to produce islet cell autoantibodies and antiGAD antibodies
What is the main role of IL-2 in T1D autoimmunity?
Activate macrophages to release IL-1 and TNF-a
What is the main role of INF-g in T1D autoimmunity?
Activate autoantigen specific T cytotoxic (CD8+) cells
What are the ICAs (Islet cell auto-antibodies) found in serum of individuals with T1D?
GAD56 (Glutamic acid decarboxylase)
IA-2 (Insulinoma antigen; tyrosine phosphatase)
IAA (Insulin auto-antibody)
Can ICAs affect the pathogenesis of T1D?
No, they are only a byproduct of T1D pathogenesis and are used only for screening.
