Innate Immunity Flashcards
What are the components of the innate immune system?
(PMN = polymorphonuclear neutrophils, M = macrophages)
What are the 2 types of effector cell lineage?
Myeloid lineage gives rise to phagocytes: PMN, monocytes/M, dendritic cells
Also gives rise to other cells such as basophils, eosinophils, mast cells
Lymphoid lineage gives rise to: NK, innate lymphoid cells, lymphocytes w ltd diversity
Describe NK cells
Recognise and kill virus-infected cells
Recognise and kill malignantly transformed cells sin prior activation
express cytotoxic enzymes for lysis
produce IFN-γ
How do NK cells and macrophages work together?
Mϕ produce IL-12 → activates NK cells
NK cells produce IFN-γ → activate Mϕ → better killing
Useful in killing stubborn bacteria like m.TB
How do NK cells recognise the different types of cells in the body?
NK cells have inhibitory and activating receptors, which give signals.
Inhibitory receptors recognise ligands on healthy cells
Activating receptors recognise infected/stressed cells
NK cells interpret these signals to give a response
Give the reason why NK cells do not attack healthy autologous cells
All healthy autologous nucleated cells have MHC I
Inhibitory receptors recognise self MHC class I
This blocks signals from activating receptors, which prevents NK cells from attacking healthy cells
Give the reason why NK cells are able to attack viral/cancer cells
Virus infected and cancer cells downregulate MHC I
Inhibitory receptors are not ligated by MHC class I
Signals from activating receptors like NKG2D are not blocked, and overwhelm signals from inhibitory receptors
NK cells can thus kill infected/tumour cells
What type of motif do inhibitory receptors contain?
Inhibitory receptors contain ITIM motif. ITIMs engage phosphatases that block signalling pathways from activating receptors
What type of motif do activating receptors contain?
ITAM: add phosphates to promote target cell killing and cytokine secretion by NKs
ITAMs= often not located in cytosolic portion of adaptor molecules (e.g. DAP 12)
ITAMs activate intracellular proteins called adaptor molecules, which transmit the signals from the receptors to the interior of the NK cells.
One such adaptor molecule is DAP 12. The ITAMs are typically located within the extracellular or transmembrane domains of these adaptor molecules, rather than in the cytosolic portion.
How do NKs actually kill target cells?
Degranulation- granules move to NK cell surface when activated, releasing mediators:
Perforin: forms pores → delivery of granzymes
Granzymes A, B, C activate caspases → apoptosis. Granzyme B triggers mitochondrial apoptosis
Delivery of perforin and granzymes must be controlled to not kill healthy cells- so its delivered at the site of contact between NK cell & target
Describe Innate lymphoid cells (ILCs)
What are Lymphocytes with limited diversity?
Combines features of T/B lymphocytes and innate cells
Express Antigen receptors (TCR, BCR)
Recognise ltd number of Ags
Respond in early stages of infection (innate response)
Give examples of lymphocytes with limited diversity
What is Chronic granulomatous disease?
Phagocytes can recognise and engulf pathogens.
BUT, hay a mutation in NADPH component
This causes a defect in oxidative burst, so phagocytosed microbes can’t be killed.
This leads to recurrent infections
What is Chediak-Higashi syndrome?
Rare genetic disease where phagocytes can recognise and engulf pathogens.
BUT, hay defective phagosome-lysosome fusion
phagocytosed microbes can’t be killed → recurrent infections
Defective gene: LYSosomal Trafficking regulator (LYST)- causes defect in lysosome fusion
Describe another clinical manifestation of Chediak-Higashi syndrome
Fewer neutrophils (neutropenia)
Giant granules and therefore giant lysosomes in the cytosol of neutrophils- this prevents fusion of the lysosome and phagosome
neutrophils can’t kill microbes
Describe Leucocyte adhesion defects
Give some complement deficiencies
Give some complement regulatory protein deficiency and the symptoms which can arise from it
