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IHO Week 4 - WLB > Antigen Presentation and Processing - Diebel > Flashcards

Antigen Presentation and Processing - Diebel Flashcards

1
Q

What are the 3 professional antigen presenting cells?

A
  1. Dendritic cells (most effective)
  2. Macrophages (particulate antigens)
  3. B-cells (soluble antigens, toxins, and viruses)
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2
Q

How does a Dendritic Cell perform antigen uptake?

A
  • Endocytosis
  • Phagocytosis
  • Pinocytosis
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3
Q

How does a Macrophage perform antigen uptake?

A

Phagocytosis

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4
Q

How does a B-cell perform antigen uptake?

A

Receptor-mediated endocytosis

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5
Q

How is activation of a Dendritic Cell achieved?

A
  • Mediated by pattern recognition receptors (PRRs)
    • TLRs
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6
Q

How is activation of a Macrophage achieved?

A
  • Meditated by pattern recognition receptors
    • TLRs
  • Enhanced by T-cell help
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7
Q

How is activation of a B-cell achieved?

A
  • Mediated by antigen recognition
    • surface immunoglobulin
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8
Q

How does the MHC Class II expression of a Dendritic cell vary?

A
  • Immature dendritic cells in the peripheral tissues
    • Constitutively express low levels of Class II molecules.
      • increases with activation
  • Mature dendritic cells in lymphoid tissues
    • Constitutively express high levels of Class II molecules.
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9
Q

How does the MHC Class II expression of a Macrophage vary?

A
  • Must be activated by phagocytosis and by cytokines to express Class II molecules.
    • increased expression with activation
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10
Q

How does the MHC Class II expression of a B-cell vary?

A
  • Constitutively expresses Class II MHC molecules (low levels)
    • increased expression with activation
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11
Q

When/What co-stimulatory activity does a Dendritic Cell produce?

A
  • Immature Dendritic Cell
    • Constitutively express low levels of B7 (CD80/86) and other co-stimulatory molecules
      • up-regulation of CD80/86 with activation
  • Mature Dendritic Cell
    • Constitutively express high levels of B7 (CD80/86)
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12
Q

When/What co-stimulatory activity does a Macrophage produce?

A
  • Must be activated to express co-stimulatory molecules (induced)
    • upregulation of CD80/86 with activation
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13
Q

When/What co-stimulatory activity does a B-Cell produce?

A
  • Must be activated by antigen binding antibody before they express co-stimulatory molecules (induced)
    • up-regulation of CD80/86 with activation
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14
Q

What are the T-cell activation properties of a Dendritic Cell?

A
  • Activate:
    • Naïve T-cells
    • Effector T-cells
    • Memory T-cells
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15
Q

What are the T-cell activation properties of a Macrophage?

A
  • Activate:
    • Effector T-cells
    • Memory T-cells
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16
Q

What are the T-cell activation properties of a B-Cell?

A
  • Activate:
    • Effector T-cells
    • Memory T-cells
17
Q

What are the two processes of MHC molecule presentation?

A
  • Cytosolic pathway:
    • presentation of antigen on MHC Class I molecules
    • requires intracellular protein synthesis of the endogenous antigen
  • Endocytic pathway
    • presentation of antigen on MHC Class II molecules
    • requires the endocytic uptake of exogenous antigen
18
Q

How are MHC Class I molecule produced?

(Hint: 5 steps)

A
  • Endogenous antigen tagged with ubiquitin
  • Tagged antigen enters proteasome
    • IFN stimulates → switch of beta subunits of proteasome to make “Immunoproteasome”
      • better at breaking down molecules for MHC molecule
    • antigen broken down into peptides
  • Peptide binds to transporter protein heterodimer complex TAP 1 & TAP 2
    • transports peptides to lumen of RER
  • Calnexin prepares and stabilizes MHC Class I for loading
  • Peptide loaded onto MHC Class I Molecules
    • ERAAP helps peptide fit into peptide-loading complex
    • once loaded the peptide-loading complex dissociates
19
Q

How is a newly assembled peptide-bound MHC Class I molecule get to the cell surface for expression?

A
  • Leaves RER packaged in a secretory vesicle
  • Vessicle undergoes further processing at Golgi complex
  • Exported from Golgi to outer cell membrane
20
Q

How are MHC Class II molecules produced?

(Hint: 7-8 steps)

A
  • Antigen internalized into APC via endocytosis or phagocytosis.
    • use clathrin-coated vesicle
  • Antigen degraded in phagolysosome or endosome.
    • low pH for degradation
  • MHC Class II receptor molecule assembled simultaneously in RER
    • alpha and beta chain coupled with an invariant chain (CD74)
    • blocks binding of endogenous antigen
  • MHC complex routed through RER to Golgi
  • Invariant chain is digested, leaving CLIP fragment
  • MHC Class II molecule catalyzes exchange of CLIP for antigenic peptide
    • HLA-DM mediates exchange
    • HLA-DO regulates exchange
  • Class II MHC-peptide is transported to plasma membrane
21
Q

What is the age of onset of diseases associated with MHC Class I Deficiency vs. MHC Class II Deficiency?

A
  • MHC Class I Deficiency
    • older age of onset
    • 3-18 yoa
  • MHC Class II Deficiency
    • younger age of onset
    • failure to thrive during infancy
22
Q

What is the disease susceptibility associated with MHC Class I Deficiency vs. MHC Class II Deficiency?

A
  • Class I
    • chronic respiratory infections
    • ability to fight some viral infections
    • deficiency does not directly decrease ability to fight off capsulated bacterial infections
    • low CD8+ T-cell count, normal CD4+ T-cell count
  • Class II
    • increased susceptibility to pyogenic and opportunistic infections
      • opportunistic pathogens like fungus
    • failure of T-cells to respond to specific pathogens
      • low CD4+ T-cell count, normal CD8+ T-cell count
    • moderate to severe hypogammaglobulinemia
23
Q

What ratio of CD4+:CD8+ T-cells would you expect in a MHC class I deficiency and why? What ratio would you expect in a MHC class II deficiency and why?

A
  • Normal ratio of CD4:CD8 = 2:1
  • Class I deficiency = 9:1
    • profound deficiency of CD8+
  • Class II deficiency = 1:3
    • profound deficiency of CD4+
24
Q

What are some causes of MHC class I and MHC class II deficiencies?

A
  • Class I
    • autosomal recessive inheritance
    • trafficking problem, trouble getting MHC Class I molecule to cell surface
  • Class II
    • autosomal recessive inheritance
    • defect in regulation of expression of the MHC Class II genes
      • transcription factors required to regulate their coordinated expression

IHO Week 4 - WLB (13 decks)

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