Lecture 12: Immunodeficiency Flashcards

1
Q

Recall the line of defences of immunity.

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2
Q

Recall the anatomical and chemical barriers of the body.

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3
Q

Recall the features of innate and adaptive immunity.

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4
Q

Recall the cells of the immune system.

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5
Q

Recall the phagocytes.

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6
Q

Recall the production of ROS by phagocytes, Recall the key enzymes.

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  • NADPH oxidase generates Superoxide O2• Forms reactive oxygen species (ROS) e.g. H2O2 & OCl-(hypochlorite)
  • NADPH oxidase inactive in unstimulated phagocytes (not fully assembled)
  • Phagocyte activation results in an NADPH oxidase assembly (p40, p47, and p67 join p22 & gp91 in phagolysosome)
  • Superoxide dismutase (SOD) converts O2-to microbicidal hydrogen peroxide (H2O2)
  • Myeloperoxidase (MPO) converts O2-to microbicidal hypochlorite (OCl-)
  • ROS in itself is insufficient to kill target microbes
  • Now thought ROS cause a K+ influx into phagolysosomes - pH↑ - optimal for antimicrobial peptides/enzymes to act
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7
Q

Recall the complement system.

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8
Q

Recall the outcomes of complement activation.

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9
Q

Recall the overview of the complement system.

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10
Q

Describe NK cells.

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  • Spontaneous capacity to kill tumour and virus-infected cells via ‘natural cytotoxicity’
    • Perforin (pores) and granzymes (cleave caspases > apoptosis)
    • unlike cytotoxic T lymphocytes (CTL), NK does not require prior host immunisation
  • Secrete high levels of IFN-γand TNF (cell proliferation, angiogenesis)
  • Considered the innate equivalent of CD8+ cytotoxic T lymphocytes (CTL)
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11
Q

Recall the cytolytic pathways of NK cells.

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  • CTL clones express a somatically rearranged T cell receptor (TCR) that recognizes MHC class I (MHC-I)-peptide complexes
  • NK cells express an array of non-rearranged, germline-encoded ACTIVATING and INHIBITORY receptors:
    • Activating receptors e.g.NKG2D bind to ligands on ‘stressed’ cells e.g. MICA
    • Inhibitory receptors e.g. Killer Ig-like receptors bind to MHC-I
  • NK cells important for catching virus-infected or tumour cells that downregulate MHC-I to evade CTL
  • CTL or NK cell activation results in the polarized release of perforin and granzymes into the target cell
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12
Q

Describe antibodies.

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13
Q

Recall antibody functions.

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14
Q

Recall how extracellular bacteria is critical for the clearance of extracellular bacteria and viruses.

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15
Q

Recall the removal of immune complexes.

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16
Q

Recall the T cells.

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  • CD4+ T-Helper (TH) lymphocytes activated by antigens on antigen-presenting cells (APCs) -secrete cytokines which stimulate different mechanisms of immunity and inflammation
  • CD8+ Cytotoxic T lymphocytes (CTL) recognise antigens on infected cells and kill these cells via cytotoxicity -perforin (pore)/granzymes (cleave caspases > apoptosis)
  • Cell-mediated immunity’ – immune responses (phagocyte activation, Ag-specific CTL responses) that don’t involve antibodies (humoral immunity)
17
Q

Recall the immunodeficiency disorder.

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18
Q

What is PID?

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19
Q

Recall the types of PID.

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20
Q

Describe the disease CGD.

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21
Q

Recall CGD pathology (molecular and cellular features).

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  • Microorganisms produce catalase -destroys any residual H2O2 in CGD phagocytes (immune evasion!)
  • Uncontrolled infections stimulate a chronic T cell-mediated immune responses
  • Granuloma formation -the characteristic histologic appearance of activated macrophages
  • IFN-γ therapy enhances transcription of NADPH oxidase complex components and superoxide production by CGD neutrophils
  • Significant improvement after CGD neutrophil superoxide production restored to ~10% of normal levels
22
Q

Describe complement deficiency.

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  • Deficiency in one or more of the complement proteins
  • Can be either inherited (primary) or acquired (secondary)
  • Often result in weaker immune response to infection
23
Q

Recall how complement deficiency relate to autoimmunity

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24
Q

What is acquired complement deficiency?

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25
Q

Recall how defects in adaptive immunity are classified.

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26
Q

Describe PAD.

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27
Q

Recall how maternal antibody plays a role in delayed diagnosis of PAD.

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28
Q

Describe Agammaglobulinemia.

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29
Q

Describe SCID.

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30
Q

Describe Familial LHL.

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31
Q

Recall the pathological features of Familial LHL.

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32
Q

Recall the mutation variants of familial HLH.

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33
Q

Recall the molecular features of HLH-associated inflammation

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34
Q

What is secondary immunodeficiency?

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  • Also know as acquired immunodeficiency i.e. ’during life’
  • Noninherited
  • Wide spectrum of presentation and severity
  • Major predisposing causes of infection and death
  • Relatively common e.g. compared to rare PIDs
  • Manifestations
    • increased frequency of common infections
    • unusual complications of infection -opportunistic infections