Lecture 12: Immunodeficiency Flashcards
Recall the line of defences of immunity.
Recall the anatomical and chemical barriers of the body.
Recall the features of innate and adaptive immunity.
Recall the cells of the immune system.
Recall the phagocytes.
Recall the production of ROS by phagocytes, Recall the key enzymes.
- 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
Recall the complement system.
Recall the outcomes of complement activation.
Recall the overview of the complement system.
Describe NK cells.
- 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)
Recall the cytolytic pathways of NK cells.
- 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
Describe antibodies.
Recall antibody functions.
Recall how extracellular bacteria is critical for the clearance of extracellular bacteria and viruses.
Recall the removal of immune complexes.
Recall the T cells.
- 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)
Recall the immunodeficiency disorder.
What is PID?
Recall the types of PID.
Describe the disease CGD.
Recall CGD pathology (molecular and cellular features).
- 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
Describe complement deficiency.
- 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
Recall how complement deficiency relate to autoimmunity
What is acquired complement deficiency?
