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IHO Week 5 > Diebel- Regulation of the Immune Response > Flashcards

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
Q

What is the mechanism for antibody-dependent B cell augmentation?

A

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
Q

What are the key features of IPEX?

A

Atopic dermatitis
watery diarrhea
FTT
autoimmune diabetes developing in infancy

27
Q

What defect causes IPEX?

A

Mutations in the gene for forkhead trxn factor Foxp3 (missense mutation)

28
Q

What does the Foxp3 do?

A

Essential for the function of CD4/CD25 T reg cells

29
Q

What would a FACs analysis show for someone w/ IPEX?

A

Lack of both CD4/25 cells and CD4 Foxp3 positive cells

30
Q

What are the hallmark labs for IPEX?

A 
High eosinophils (normal 15%)
Elevated IgE
31
Q

Do individuals suffering from IPEX produce autoantibodies? How does this occur?

A

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
Q

What is the treatment for IPEX?

A

Immunosuppressive therapy (cyclosporine and tacrolimus)

Bone marrow transplant from HLA-identical donor

IHO Week 5 (9 decks)

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