Innate Immunity Flashcards
Components of innate immune system
Barriers
Cells: myeloid lineage, lymphoid lineage
Soluble molecules
Myeloid lineage
Phagocytes (neutrophils, macrophages, dendritic cells), mast cells, eosinophils, basophils
Lymphoid lineage
NK cells, innate lymphoid cells, lymphocytes with limited diversity
NK cells
- Kill tumour cells and virus infected cells
- Express cytotoxic cells
- Release produces interferon gamma
- They contain granules containing perforin and cytolytic enzymes (granzymes a +b)
- Can kill cells without prior activation
- Work with macrophages: Macrophages produce cytokine IL-12 which activates NK cells which produce interferon gamma which activates macrophages
How do NK cells recognise healthy cells?
Healthy cells express MHC class 1 on surface
NK cell inhibitory receptor contains an ITIM motif which recognises MHC class 1
This activates protein tyrosine phosphatase which removes the phosphate group from the activating receptor, which stops it activating a response
Activating signals < inhibitory signals
How do NK cells recognise infected cells?
Infected cells reduce their expression of MHC class 1 on surface = less binding of inhibitory receptor
Infected cells also express ligands on surface which are recognised by the activating receptor ITAM motif
This activates protein tyrosine kinase which adds a phosphate group to the activating receptor, initiating the activating cascade
Activating signals > inhibitory signals
How do NK cells kill cells?
They have granules containing perforin and granzymes a and b in their cytosol
Delivered at site of contact between NK cell and target cell to prevent killing of neighbouring healthy cells
Perforin creates holes in infected cells membrane so granzymes can enter and trigger apoptosis
Granzymes activates caspases which kill the cell by cleaving its DNA
Granzyme B initiates the mitochondria apoptotic pathway
What are innate lymphoid cells?
These are cells of the innate immune system
These do not need activating
They do not express T cell receptor
MAIN MECHANISM : PRODUCE CYTOKINES
ILC 1
Th1 like
Defence against viruses
ILC 2
Th2 like
Allergic inflammation, defence against helminths
ILC 3
Th17 like
Gut protection against bacterial infection
Lymphocytes with limited diversity
Lymphocytes which express both T cell receptor and B cell receptors
Respond in early stages of infection
Recognise limited number of antigens
Human NK cell deficiency
When there is a deficiency or absence in NK cells
Leads to patient getting frequent and more fatal viral infections such as herpes simplex virus
Chronic granulomatous disease
When cell can’t produce reactive oxidative species needed to kill pathogens in phagosomes
Chediak-Higashi syndrome
When lysosomes fuse with each other instead of fusing with phagosomes = pathogen in phagosome can’t be lysed
Neutrophils have giant granules in cytosol
