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

Regulation of the Immune Response - Diebel Flashcards

1
Q

What determines the nature of the immune response?

(Hint: 5 things)

A
  1. The form, dose, and route of administration of the antigen
  2. The state of the antigen-presenting cell (APC)
  3. The genetic background of the individual
  4. Any history of previous exposure to the cognate antigen
  5. Any concurrent infections that the individual may have
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2
Q

When will the outcome of an interaction between and a CD4+ T cell will lead to T cell activation vs. tolerance through anergy?

A
  • T-cell activation occurs when:
    • Strong expression of MHC II and co-stimulatory molecules
      • CD86
      • CD40
      • CCR7
    • Microbial or self-derived stimuli (danger signals)
    • Antigen internalized → increased NF-KB
    • Production of proinflammatory cytokines (IL-12, TNF-alpha)
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3
Q

When will the outcome of an interaction between and a CD4+ T cell will lead to tolerance through anergy vs. T cell activation?

A
  • Tolerance through anergy when:
    • surface molecules such as:
      • E-cadherin
      • PD-1 L
      • CD103
      • CD152 (CTLA-4)
      • ICOS-L (CD275)
    • cytokines including:
      • IL-10
      • TGF-ß
    • Low levels of:
      • ​CD86
      • MHC II
        CD40
      • CCR7
    • Decreased NFKß activity
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4
Q

What are the four different types of Treg effector mechanisms used to control the proliferation and actions of other T cell populations?

A
  • Immunosuppressive cytokines (blocks Th1)
    • IL-10
    • TGF-ß
    • IL-35
  • IL-2 consumption
    • soaks up excess IL-2 via IL-2R (CD25)
  • Cytolysis
    • granzyme-mediated lysis
  • Modulation of DC maturation and function
    • binds CD via CD152 (CTLA-4) & CD80/86
    • allows DC to convert tryptophan → kynurenin (growth inhibitory signal)
      • leads to T cell cycle arrest
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5
Q

What is the function of IL-2?

A
  • Stimulates the growth and differentiation of helper, cytotoxic, and regulatory T cells.
  • Activates macrophages.
  • Stimulates proliferation and differentiation of mature T and B cells.
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6
Q

What is the function of IL-10?

A
  • Anti-inflammatory
  • Blocks the generation of Th1 CD4+ T cells.
  • Similar in function to TGF-β in inhibiting inflammation.
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7
Q

What is the function of IL-12?

A
  • Important factor in inducing the production of Th1 CD4+ T cells.
  • Induced IFNγ production by Th1 CD4+ T cells and NK cells.
  • Enhances NK cell and CD8+ cytotoxic T cell activity.
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8
Q

What is the function of IL-35?

A
  • suppresses inflammatory responses of immune cells
  • induces proliferation of Treg cell populations but reduces activity of Th17 cell populations
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9
Q

What is the function of TGF-ß?

A
  • block the activation of lymphocytes and monocyte derived phagocytes
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10
Q

What is the function of CCR7 (CD197)?

A
  • control the migration of memory T cells home to secondary lymphoid organs, such as lymph nodes
  • stimulate dendritic cell maturation
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11
Q

What is the function of CD25?

A
  • alpha chain of the high-affinity receptor for IL-2
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12
Q

What are the four different types of B cell tolerance mechanisms after B lymphocyte binds self-antigen to it’s antibody (self-reactive receptor)?

A
  • Clonal Deletion
    • Induction of apoptosis via inhibition of survival signals OR activation of death receptors
  • Receptor Editing
    • Continued V(D)J recombination to avoid self-reactivity
  • B-cell Intrinsic Mechanisms
    • anergy
    • downregulation of the BCR
    • upregulation of CD5
  • B-cell Intrinsic Mechanisms
    • Lack of T-cell help or survival factors
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13
Q

Which types of T cells produce IL-2?

A
  • Th0 T cells
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14
Q

Which types of T cells produce IL-4?

A
  • Th0 T cells
  • Th2 T cells
  • NK cells
  • Specialized macrophages (M2)
  • Basophils
  • mast cells
  • bone marrow stromal cells.
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15
Q

Which types of T cells produce IL-5?

A
  • Th2 T cells
  • mast cells
  • eosinophils
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16
Q

Which types of T cells produce IL-10?

A
  • Treg T cells
  • Th2 T cells
17
Q

Which types of T cells produce IL-13?

A
  • Th2 T cells
18
Q

Which types of T cells produce IL-17?

A
  • Th17 T cells
19
Q

Which types of T cells produce IL-35?

A
  • Treg T cells
20
Q

Which types of T cells produce IFN-γ?

A
  • Th0 T cells
  • Th1 T cells
  • NK cells
21
Q

Which types of T cells produce TNF-α?

A
  • Th1
22
Q

Which types of T cells produce TGF-β?

A
  • Treg T cells
23
Q

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

A
  • Antibody blocking
    • soluble Ig bound to antigen binds to and blocks membrane Ig
    • plasma cells run out of fuel because they no longer have available antibody (it is all bound)
  • Receptor cross-linking
    • Membrane Ig binds antigen
    • Soluble IgG binds SAME antigen AND attaches to transmembrane protein that initiates inhibitory signal cascade to nucleus
24
Q

A defect in the production of what cell types can lead to the immune dysregulation syndrome known as IPEX?

A
  • In humans, missense or frameshift mutations in FOXP3 result in loss of function of Tregcells and uninhibited T-cell activation
    • FOXP3 is essential for the function of CD4+/CD25+ Treg cells.
  • Treg cells are anergic in vitro.
  • They fail to secrete IL-2 or proliferate in response to ligation of their T-cell receptors
  • Depend on the IL-2 generated by activated CD4+ T cells to survive and exert their function.
25
Q

What abnormalities can be present in a WBC differential associated with IPEX?

A
  • normal white blood cell count
  • normal hemoglobin count
  • normal platelet count
  • The percentage of eosinophils in the blood was high at 15% (normal <5%)
  • IgE was also elevated
26
Q

Do individuals suffering from IPEX produce autoantibodies? If so, why?

A
  • Yes:
    • Autoantibodies can be found against glutamic acid decarboxylase (the GAD65 antigen) and against pancreatic islet cells.
  • Why:
    • Failure of peripheral tolerance due to defective Treg cells.
    • Consequently, T and B cells escaped central tolerance and exit to the periphery.
27
Q

What are the physical manifestations of IPEX?

A
  • an intractable watery diarrhea
    • leads to failure to thrive
  • dermatitis
  • autoimmune diabetes developing in infancy
28
Q

What is the treatment for IPEX?

A
  • Immunosuppressive therapy
  • Bone marrow transplant
  • Intravenous immunoglobulin (IVIg)
29
Q

A defect in the production of what cell types can lead to the immune dysregulation syndrome known as APECED?

A
  • Defect in production (negative selection) of T-cells in the thymus
  • Autosomal recessive inheritance of defective AIRE gene on chroms 21
    • consequently unable to weed out T cells that react to self-antigen (error in negative selection) in the thymus
    • cells are not able to display/react to self-antigen properly
30
Q

What abnormalities can be present in a WBC differential associated with APECED?

A

twice as many T4/T8 cells

31
Q

Do individuals suffering from APECED produce autoantibodies? If so, why?

A
  • Yes, a wide range of autoantibodies against:
    • organ-specific antigens of the endocrine glands
    • antigens in the liver and skin
    • blood cells such as platelets
  • Why:
    • T cells react to self-antigen because they were not trained properly
32
Q

What are the physical manifestations of APECED?

A
  • abnormalities of various ectodermal elements such as fingernails, teeth, and skin
    • nail dystrophy
    • perioral candidiasis
    • hypothyroidism/hypoparathyroidism
    • serum antibodies
  • They also have an increased susceptibility to infection with the yeast Candida albicans.
33
Q

What is the treatment for APECED?

A
  • The treatment of APECED is directed at treating the specific problems:
    • replacing the various hormones that are in short supply
    • giving insulin for the diabetes
    • treating the yeast infections
    • etc.
  • There is no known cure for APECED.

IHO Week 5 - WLB (6 decks)

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