Diebel- Regulation of the Immune Response Flashcards
Describe the process of activation between an APC cell and a CD4 T cell.
APC activated by contact w/ antigen> APC goes from making low MHCII/B7 to HIGH levels> HIGH levels MCHII/B7> Robust immune response> Interaction between CD40L/CD40> IL-12 (survival and growth of CD4Th1)
When does tolerance occur between APC and CD4 T cells?
LOW MHC + LOW B7–> no co-stimulation–> anergy
What is CCR7?
Traffics APCs from tissue to secondary lymphoid organs
What happens when there’s a defect in CCR7?
You can’t traffic to the lymph nodes
What does CD44 do?
Expressed early in T cell diff, helps T cells to escape bone marrow and go to thymus
What are the 4 different types of T reg effector mechanisms used to control proliferation and actions of T cell populations?
- Immunosuppressive cytokines- Block ability to make/respond to IL-2
- IL-2 consumption- high affinity CD 25
- Cytolysis- granzyme
- Modulation of DC maturation and function- kynurenin
IL-2
Supports growth and expansion of most T cell populations, NK cells and B cells
IL-10
Shuts of T cells that are already active and block the ability for more T cells to become active
IL-12
Supports survival and growth, specifically of Th1 and blocks growth of Th2
IL-35
Increases T reg prolifeartion–> increases IL-10 production
TGF-B
Blocks IL-1 and IL-2 dependent T cell prolifeartion
IL-35 and TGF-B combination
Converts Th-1 to Treg
CCR7
Located on APCs, activated for IR, traffics APC from tissue to secondary lymphoid organs
CD25
IL-2R
Any cell expressing CD25 can respond to IL-2
What are autoantibodies?
Antibodies that recognize self-antigens and pose a threat to the organism
What causes Grave’s disease?
Autoantibodies act as agonists for the receptor for thyroid stimulating hormone leading tot he over production of thyroid hormones
What causes blistering skin disease?
Autoantibodies that recognize adhesion molecules in the epidermis
What causes SLE?
Autoantibodies that effect multiple organs
What are the 4 mechanisms of B cell self tolerance?
- Clonal deletion- induction apoptosis via inhibiton of survival signals/activation death receptors
- Receptor editing- continued V(D) J recombination to avoid self-reactivity
- Intrinsic- Anergy, down regulation of the BCR, upregulation of CD5
- Intrinsic- Lack of T cell help or survival factors
What cytokines does Th1 produce?
IL-2
IFNy
TNFB
TNFa
What cytokines does Th2 produce?
IL-4 IL-5 IL-9 IL-10 IL-13
What cytokines does Th17 produce?
IL-17
IL-21
IL-22
TNF-a
What cytokines does Treg produce?
IL-10
IL-35
TGF-B
What are the two mechanisms of antibody-dependent B cell suppression?
- Antibody blocking: IgG binds Ag so well–> immune complex formation w/ Ag–> BCR can’t respond
- Receptor crosslinking: IgG crosslinks Ag receptor w/ Fc receptor on same B cell–> activating signal on BCR, inhibiting signal on FC–> inhibitory signal overrides
What is the mechanism for antibody-dependent B cell augmentation?
Secreted IgM binds to antigen–> helps facilitate interaction of FDC binding to antigen and complement deposition on antigen
IgM and FDC recognize complement (CR2) bound to antigen–> pos signal to augment reponse
What are the key features of IPEX?
Atopic dermatitis
watery diarrhea
FTT
autoimmune diabetes developing in infancy
What defect causes IPEX?
Mutations in the gene for forkhead trxn factor Foxp3 (missense mutation)
What does the Foxp3 do?
Essential for the function of CD4/CD25 T reg cells
What would a FACs analysis show for someone w/ IPEX?
Lack of both CD4/25 cells and CD4 Foxp3 positive cells
What are the hallmark labs for IPEX?
High eosinophils (normal 15%) Elevated IgE
Do individuals suffering from IPEX produce autoantibodies? How does this occur?
YES
Autoantibodies against GAD654 antigen and pancreatic islet cells
Lack of Foxp3 expressing T reg cells is sufficient to break self-tolerance and induce autoimmune disease–> uninhibited T cell activation
What is the treatment for IPEX?
Immunosuppressive therapy (cyclosporine and tacrolimus)
Bone marrow transplant from HLA-identical donor
