Diebel- Regulation of the Immune Response Flashcards

1
Q

Describe the process of activation between an APC cell and a CD4 T cell.

A
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)
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2
Q

When does tolerance occur between APC and CD4 T cells?

A

LOW MHC + LOW B7–> no co-stimulation–> anergy

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3
Q

What is CCR7?

A

Traffics APCs from tissue to secondary lymphoid organs

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4
Q

What happens when there’s a defect in CCR7?

A

You can’t traffic to the lymph nodes

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5
Q

What does CD44 do?

A

Expressed early in T cell diff, helps T cells to escape bone marrow and go to thymus

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6
Q

What are the 4 different types of T reg effector mechanisms used to control proliferation and actions of T cell populations?

A
  1. Immunosuppressive cytokines- Block ability to make/respond to IL-2
  2. IL-2 consumption- high affinity CD 25
  3. Cytolysis- granzyme
  4. Modulation of DC maturation and function- kynurenin
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7
Q

IL-2

A

Supports growth and expansion of most T cell populations, NK cells and B cells

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8
Q

IL-10

A

Shuts of T cells that are already active and block the ability for more T cells to become active

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9
Q

IL-12

A

Supports survival and growth, specifically of Th1 and blocks growth of Th2

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10
Q

IL-35

A

Increases T reg prolifeartion–> increases IL-10 production

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11
Q

TGF-B

A

Blocks IL-1 and IL-2 dependent T cell prolifeartion

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12
Q

IL-35 and TGF-B combination

A

Converts Th-1 to Treg

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13
Q

CCR7

A

Located on APCs, activated for IR, traffics APC from tissue to secondary lymphoid organs

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14
Q

CD25

A

IL-2R

Any cell expressing CD25 can respond to IL-2

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15
Q

What are autoantibodies?

A

Antibodies that recognize self-antigens and pose a threat to the organism

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16
Q

What causes Grave’s disease?

A

Autoantibodies act as agonists for the receptor for thyroid stimulating hormone leading tot he over production of thyroid hormones

17
Q

What causes blistering skin disease?

A

Autoantibodies that recognize adhesion molecules in the epidermis

18
Q

What causes SLE?

A

Autoantibodies that effect multiple organs

19
Q

What are the 4 mechanisms of B cell self tolerance?

A
  1. Clonal deletion- induction apoptosis via inhibiton of survival signals/activation death receptors
  2. Receptor editing- continued V(D) J recombination to avoid self-reactivity
  3. Intrinsic- Anergy, down regulation of the BCR, upregulation of CD5
  4. Intrinsic- Lack of T cell help or survival factors
20
Q

What cytokines does Th1 produce?

A

IL-2
IFNy
TNFB
TNFa

21
Q

What cytokines does Th2 produce?

A
IL-4
IL-5
IL-9
IL-10
IL-13
22
Q

What cytokines does Th17 produce?

A

IL-17
IL-21
IL-22
TNF-a

23
Q

What cytokines does Treg produce?

A

IL-10
IL-35
TGF-B

24
Q

What are the two mechanisms of antibody-dependent B cell suppression?

A
  1. Antibody blocking: IgG binds Ag so well–> immune complex formation w/ Ag–> BCR can’t respond
  2. Receptor crosslinking: IgG crosslinks Ag receptor w/ Fc receptor on same B cell–> activating signal on BCR, inhibiting signal on FC–> inhibitory signal overrides
25
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
26
What are the key features of IPEX?
Atopic dermatitis watery diarrhea FTT autoimmune diabetes developing in infancy
27
What defect causes IPEX?
Mutations in the gene for forkhead trxn factor Foxp3 (missense mutation)
28
What does the Foxp3 do?
Essential for the function of CD4/CD25 T reg cells
29
What would a FACs analysis show for someone w/ IPEX?
Lack of both CD4/25 cells and CD4 Foxp3 positive cells
30
What are the hallmark labs for IPEX?
``` High eosinophils (normal 15%) Elevated IgE ```
31
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
32
What is the treatment for IPEX?
Immunosuppressive therapy (cyclosporine and tacrolimus) Bone marrow transplant from HLA-identical donor