Innate immunity Flashcards
Innate barriers for skin
Epithelial cells, Flow of air, Fatty acids, Antibacterial peptides, Normal flora
Innate barriers for gut
Epithelial cells, Flow of fluid, low pH, Pepsin enzyme, Antibacterial peptides, Normal flora
Innate barriers for lungs
Epithelial cells,
Mucus movement by cilia
Innate barriers for eyes/nose
Epithelial cells,
Tears,
Nasal cilia
Lysozyme in tears
How omega 3 fatty acids influence innate immunity
Reduce proinflammatory cytokine production, antidiabetic
How complex plant polysaccharides influence innate immunity
Tumour suppression, cytokine production, reduced oxidative DNA damage
What are phagocytes called in
- blood
- liver
- skin
- CNS
- lung
- blood: monocyte
- liver: Kupffer cells
- skin: Langerhans cells
- CNS: microglial cells
- lung: alveolar macrophage
How phagocytes distinguish self from non-self
PRR on phagocyte receptors recognise PAMPs
How phagocytes kill pathogens
- Acidic environment
- Respiratory burst
- Contain lysosomes which destroy pathogen
- Induce secretion of pro-inflammatory cytokines
- activated NFkB
What happens during respiratory burst
- Activated NADPH converts O2 to superoxide O2-
- O2s converted to H2O2 by superoxide dismutase
- H2O2 converted to hypochlorite ions and hydroxyl radicals by peroxidase enzymes and iron
Function of NFkB
Controls DNA transcription, cytokine production, cell survival
Can be first responder to harmful cellular stimuli.
Regulates genes involved in innate and adaptive immune response: T cell development, maturation, proliferation
Induces secretion of pro-inflammatory cytokines
What induces NFkB
Reactive oxygen species, TNF-alpha, IL-1beta, bacterial lipopolysaccharides, ionising radiation, cocaine, etc
Which cytokines are secreted by macrophages
IL-1, 6, 8, 12, TNF-alpha
IL-1, 6 activate lymphocytes
IL-8 recruits neutrophils, basophils, T cells
IL-12 activates NK cells
TNF-alpha increases vascular permeability (also involved in shock)
What are toll-like receptors
Recognise patterns not found in vertebrates (characteristic components of pathogenic organisms)
Induce inflammatory cytokines
How long does innate immunity take to respond
Rapid: 0-4h
What activates and inhibits NK cells
Activation: not required
Inhibition: MHC-1 (often suppressed in virally infected or cancerous cells)
How to NK cells kill virus-infected cells
They do not recognise specific Ag (no TCR/BCR equivalent)
Express Fc-gamma-RIII: receptor for IgG1 and IgG3 (on viral protein at cell suraces)
Fc-gamma-RIII binds to IgG through cross linking
Cell death through apoptosis (same mechanism as CD8 cells)
NK cells also secrete IFN-gamma, which activates macrophages. Macrophages secrete TNF-alpha and IL-12 which further promote action of NK cells
List the phagocytes and where they are found
MACROPHAGES: in connective tissue e.g. GI tract, bronchi, liver, spleen
GRANULOCYTES: NEUTROPHILS, EOSINOPHILS, BASOPHILS: not present in healthy tissue
DENDRITIC CELLS: present in healthy tissue in contact with external environment (skin, nose, lungs, stomach, intestines) + blood (immature in blood)
What parts of innate and adaptive immunity are used against viruses
Innate:
- interferon (inhibits virus replication, increases expression of MHC-1 and MHC-2)
- NK cells (apoptosis)
Adaptive:
- CD8 cells
- Complement
Note: Ab are not so useful for defending bodies against viruses
Functions of APCs (3 types of cells)
DC: activate T cells to move to site of infection. Constant updating of what’s happening at site of infection.
Macrophages: Restimulate activated T cells (T cells undergo apoptosis once stimulus is removed)
B cells: Express high levels of MHC to present antigen to T helper cells. High affinity for antigen due to somatic hypermutation
Describe intrinsic cell death pathway
Mitochondria swell and leak, releasing cytochrome C.
Cytochrome C binds to Apaf-1
The resulting complex activates pro-caspase 9 and 3, which cleaves and releases CAD.
CAD enters nucleus and cleaves DNA
Describe extrinsic cell death pathway
Fas ligand binds to and trimerises Fas.
Clustering of death domains in Fas cytoplasmic domains allows Fas to recruit FADD via its death domain.
Clustered death effector domains of FADD recruit pro-capsase 8.
3 functions of inflammation
- Induce local blood clotting
- Recruit effector cells from blood into infection site
- Promote repair of injured tissue
