innate immunity Flashcards
monocytes
circulating precursors to dendritic and macrophages
macrophages
tissue resident around the body, phagocytic and antigen presenting
dendritic cell
differentiate in the tissue, phagocytic and antigen presenting, travel to lymph nodes to activate t cells
neutrophils
circulating cells, highly phagocytic granulocytes
eosinophils
circulating cells, responed to IgE, can degranulate to remove parasites
basophil
circulating granulocytes in very low numbers
mast cell
tissue resident, source of cytokines, can degranulate
t lymphocytes
helper and cytotoxic, recircultae through lymph nodes, activated by dendritic cells
natural killer cells
innate immune cells which infected cells using granule contents
b lymphocytes
produce antibodies, activated by t cells, become antibody secreting plasma cells
innate immunity
barriers and deffences already in the tissue and the blood stream
adaptive immunity
t and b cells, focused at specific pathogen, antibodies or memory response
what happens if barriers are breached
- fragments of cells are released due to damage
- they bind to receptors
- induces inflammation through inflammatory cytokine release
4 cardial signs of inflammation
- redness
- heat
- swelling
- pain
pro inflammatory cytokines
- Interleukin - IL-1B, IL6
- Tumour necrosis factor - TNFa
effects of pro-inflammatory cytokines on the tissue
- pro-inflammatory cytokines are released into the tissue
- can act on the endothelial cells of blood vessels to weaken the tight junctions between cells = more permeable
- cause blood vessels to increase in diameter, increasing and slowing blood flow
- swelling in tissue can sensitise nerve endings in the skin, causing pain
what are DAMPs
danger-associated molecular pattern molecules
what are PAMPs
pathogen associated molecular patterns
- resident in barrier tissue with pattern recognition receptors on them
how to toll like receptors work
- change to transcription and cytokine released
1. recognition of pathogen transmits signal to the nucleus
2. protein NFkB assembles and bind the DNA instructing the cells to produce new proteins
3. include pro-inflammatory cytokines and cell surface molecules
how do phagocytic receptors work
- induce internalisation of pathogen
1. pathogen is recognised by receptors and phagocytosis is induced
2. pathogen is internalised in a phagosome, fuses with a lysosome containing antimicrobial peptides, lysozyme and nitric oxide
3. pathogen is broken down
what are the external receptors
- toll like receptors
- phagocytic receptors
what are the internal receptors
- cytoplasmic
- endosomal
what are complement proteins
collection of small proteins produced by the liver which circulate in the blood and are active once in the tissue
what are chemotaxis
controlled by chemokines, depending on tissue and point of infection different chemokines are produced
stages of neutrophil recruitment
- neutrophils circulate in the blood and bind weakly to E-selectin via their proteoglycans
- infection - pro-inflammatory cytokine and chemokines are released
- IL-1b and TNFa up regulate adhesion molecules on the blood vessels at the sight of inflammation, CXCL8 adheres to the lumen of the vessels
- neutrophils attached to E-selectin and rolls along the vessels before attaching via ICM-1 and LFA-1. neutrophils follow the chemokine to the site of infection
what are in the neutrophil granules
antimicrobial proteins and peptide which disrupt and digest microbes
how do adhesion molecules work
- neutrophils recognise adhesion molecules the proteoglycans and LFA-1
- toll like receptors cause macrophages to produce chemokines CXCL8, dense at macrophage where bacteria is, diffuse through into the tissue, macrophages follow the chemokines from the blood vessels to the macrophages
- neutrophils and phagocytic - engulf the bacteria
what does TNFa do when it binds to the cytokines
produces nitric oxide - causes vasodilation
how does intracellular pathogen recognition work
- damage is recognised by DAMP receptors
- this induces cytokine release
- the pathogens inside the cells must be recognised a different way by internal pathogen recognition receptors
stages of toll like receptors
- recognition of the pathogen within the endosome transmits a signal to the nucleus
- a protein called IRF assembles and bonds the DNA instructing the cells to produce new proteins
- these are INFa and INFb
how do NOD receptors work (intracellular receptor)
- lead to NFkB activation and in some cases IRF
- induces transcription of pro-inflammatory cytokines and defensisins
how do RIGs work (intracellular receptors)
- recognition of viral RNA in cytoplasm activates IRF3
- induces expression of interferon beta
what are the effects of interferons
- INFb signals to cells around: blokes viral protein synthesis, promotes viral RNA degradation, inhibits assembly, MHC expression
- induces chemokines to recruit lymphocytes
- activated NK cells
- activates dendritic cells and macrophages
what do MHCI cells do
- constantly put peptides on cells
- expressed by all nucleated cells
- allows constant surveillance
what do MHCII cells do
only expressed by antigen presenting cells
stages of MHCI processing
- proteins in the cytosol are continually sampled through the proteasome and broken down into small proteins
- small peptides are passed through the endoplasmic reticulum to be placed on MHCI
- MHCI delivered to the surface for presentation - immune system detects virus being presented on the cells recognises it as not self
NK cells
- have inhibitory and activating receptors to identify when a cell is infected with a pathogen
- granules kill cells and produced interferon
- granules of perforin and granzyme
what does perforin do
proliferates the cell to insert granzymes into the cell with the virus into to digest the virus
nk cell interaction - cell survival
- normal levels of MHCI presenting self-peptide on cells induces a negative signal which overcomes the signal from activating receptor
nk cell interaction - cell undergoes apoptosis
- altered MHCI on cell isn’t recognised
- positive signal from activating receptors activates the NK cells
- absence of reduction of MHCI allows the activating signal to induce the NK cell
stages of NK cell interaction
- the virus attaches to the cell and infects it
- the viral protein in the cytoplasm can become processed through the MHCI pathway
- additionally recognition of the virus by TLRs indues the release of IFNb which signals both paracrine to neighbouring cells and autocrine
- this induces the release of IFNa and makes neighbouring cells less permissive to viral infection
- NK cells release perforins and granzymes which kill the virus infected cell
what does INFa production do to NK cells
- INFa production recruits NK cells
- upregulates NHCI and NK activating ligands
stages of recognition of intracellular bacteria
- whilst extracellular they can be recognised by receptors and phagocytosed
- the phagocyte will try and kill the bacteria by fusing a lysosome, some bacteria thrive in the acidic conditions and survive
- other can directly penetrate or escape from phagosomes into the cytoplasm
- when in the cytoplasm the bacteria can be recognised by receptors such as NOD which activate NFkB
- pro inflammatory cytokine are released by depending on pathogen IL-12 is also secreted
stages of NK cells enhancing macrophage function
- macrophages produce chemokine and IL12 after phagocytosing the pathogen
- NK cells are attracted and activated by the IL12 and IL15 to proliferate and produce IFNy
- INFy activates macrophages to make them more aggressive and enhance pathogen destruction
what is autophagy
the recognition of macrophages by NOD2
what are the stages of autophagy
- stalled phagosomes and free bacteria can be engulfed again through autophagy - recycling components of cell to keep it healthy
- they autophagosomes merges with a lysosome and the pathogen is destroyed allowing it to present antigens on MHCII
- antigen is presented on MHCII
what do the dendritic cells do in innate immunity
they connect innate immunity to adaptive immunity
