Innate immunity Flashcards
What are examples of effector cells, in specific phagocytes, that stem from the myeloid lineage?
- Polymorphonuclear cells
- Monocytes
- Dendritic cells
What are examples of effector cells that are part of the myeloid lineage and are not phagocytes?
- Basophils
- Eosinophils
- Mast cells
What are examples of effector cells that stem form the lymphoid lineage?
- Natural killer cells
- Innate lymphoid cells
- Lymphoids
What do natural killer cells recognise and do and example cells?
Recognise infected & stressed cells and kill them
-Kill virus-infected cells
-Kill malignantly transformed cells(tumour cells)
What do enzymes do natural killer cells produce and what do they do to target cells?
express cytotoxic enzymes (lyse target cells)
What protein do natural killer cells produce?
produce interferon-γ (IFN-γ)
How are malignant tumour cells killed by natural killer cells?
Kill malignant tumour cells without prior activation
In comparison to malignant tumour cells, how are target cells killed by natural killer cells?
CD8+ T cells need to be activated and differentiate into CTL (cytotoxic T lymphocytes) to kill target cells
What are there many of in the cytosol of natural killer cells?
Many granules in the cytosol
What proteins are present in the cytosol of natural killer cells
- Perforin
- Cytolytic enzymes
What are the specific cytolytic enzymes in the cytosol of natural killer cells?
Granzymes A and B
How does macrophage cooperation work in natural killer cells?
- NK cells collaborate with macrophages in killing microbes
- Macrophages produce IL-12 which activates natural killer cells
- Natural killer cells produce IFN-γ which activates macrophages, allowing enhanced macrophage killing of phagocytosed microbes
What are inhibitory receptors on natural killer cells?
- KIRs (killer inhibitory receptors)
- NKG2A (C type lectin receptors)
- Leucocyte Ig-like receptors
What do inhibitory receptors on natural killer cells recognize?
Inhibitory receptors recognise ligands on healthy cells
What are the activating receptors on natural killer cells?
- NKG2D, KIRs, CD16
- Adaptor proteins: DAP10, DAP12
What do activating receptors on natural killer cells recognise?
- Activating receptors recognise infected/stressed cells
What do all autologous nucleated cells have?
All healthy autologous nucleated cells have MHC I
What happens in the interaction between inhibitory receptors on natural killer cells and MHC class I
- Inhibitory receptors recognise self MHC class I
- This results in a blockafe of signals from activating receptors
- Ultimately leading to NK cells not attacking healthy autologous cells
What do virus infected cells and malignant(cancer) cells do to MHC I?
Downregulate MHC I
What are the steps involved in the recognition of target cells by natural killer cells?
- Activating receptors (NKG2D) recognise ligands that
are induced on unhealthy cells (stressed, infected by
microbes, malignantly transformed cells) - Signals from activating receptors overwhelm the signals from inhibitory receptors, especially if MHC I is also reduced or lost in unhealthy cells
–Virus inhibits MHC I expression
-NK cells attack and kill virus infected / cancer cells
What is the structure of an inhibitory receptor on natural killer cells?
-Extracellular:
–KIR3DL
–KIR2DL
-Intracellular:
–ITIM(Immunoreceptor tyrosine-based inhibitory motif
What is the structure of an activatory receptor on natural killer cells?
-Extracellular:
-KIR3DS
-KIR2DS
-Intracellular:
–ITAM(Immunoreceptor tyrosine-based activation motif)
–DAP12
What do ITIMs engage in?
ITIMs engage phosphatases that block the signalling
pathways triggered by activating receptors
What do ITAMs engage in and what does this promote?
ITAMs engage protein tyrosine kinase-mediated signalling events (promote target cell killing and cytokine secretion by NK cells)
Where are ITAMs often located?
ITAMs are often located not in activating receptors but in cytosolic portion of adaptor molecules (e.g. DAP12)
How do perforins work?
-Forms pores
–Delivery of granzymes
What type of granzymes are there and what do they initiate?
-Granzymes A,B and C
–Initiate apoptosis
Where are perforins and granzymes delivered and what is this to prevent?
Delivered at the site of contact between NK cell & target
-Prevents killing of neighbouring healthy cells
What do granzymes activate and what does this lead to?
Granzymes activate caspases which lead to apoptosis
What can granzyme B trigger?
Can trigger mitochondrial apoptotic pathway
What do innate lymphoid cells have a similar function to?
-Similar function to lymphocytes
What do innate lymphoid cells not express?
do not express TCRs (T cell receptors)
Do innate lymphoid cells proliferate of differentiate?
no clonal expansion (proliferation) & no differentiation
What is the main mechanism in innate lymphoid cells?
main mechanism: produce cytokines
What are the different type of innate lymphoid cells dependent on?
different types of ILCs depending on type of cytokines
What are the different types of Innate lymphoid cells and what T helper cell are they like?
-ILC1 is Th1 like
-ILC2 is TH2 like
-ILC3 is TH17 like
What ILC are natural killer cells related to?
NK cells are related ILC 1
What cytokines is ILC1 linked with?
IFN-γ
What cytokines is ILC2 linked with?
IL-5, IL-13
What cytokines is ILC3 linked with?
IL-17, IL-22
What is IFN-γ involved in the defence against?
Defence against viruses
What is IL-5 and IL-13 involved in the defence against?
Defence against helminths, allergic inflammation
What is IL-17 and IL-22 function?
Intestinal barrier function and lymphoid organogenesis
What do both T/B lymphocytes and innate cells express?
Both express Ag receptors (TCR and BCR)
What is there a mutation in and a defect in chronic granulomatous disease and what does this mean?
-Mutation in NADPH component
-Defect in oxidative burst
-This means phagocytosed microbes can’t be killed
What is defective in chediak higashi syndrome and what does this mean?
-Defective Phagasome-lysosome fusion
-This means phagocytosed microbes can’t be killed
What happens to the neutrophil count in chediak-Higashi syndrome?
Decreased number of neutrophils(neutropenia)
How does chediak-Higashi syndrome appear on a blood smear?
giant granules in the cytosol of neutrophils
What do giant granules in a blood smear of neutrophils suggest?
Giant granules = Giant lysosomes
What gene is defective in chediak-Higashi syndrome?
-Lysosomal trafficking regulator(LYST)
-Defect in lysosome fusion
How do neutrophil chemotaxis work?
- Rolling
- Integrin activation by chemokines
- Stable adhesion
- Migration through endothelium
What does a deficiency in C2, C4, C1q complement result in?
Result in SLE-like syndrome
What does a C3 complement protein deficiency result in?
frequent serious infections with pyogenic
bacteria (e.g. Staphylococcus aureus, etc.)
What does a deficiency in C5-C9(MAC) deficiency result in?
disseminated infections with
Neisseria (N. meningitidis, N. gonorrhoeae)
What complement protein deficiency causes hereditary angioedema?
C1 INH deficiency
What is there an incresed clevage of in C1 INH deficiency?
Increased cleavage C4, C2
What are the clinical presentations of hereditary angioedema?
oedema in skin/mucosa → abdominal pain, vomiting, diarrhoea, airway obstruction
What deficiency causes paroxysmal nocturnal haemoglobinuria and what recurring event occurs?
DAF, CD59 deficiency
-Recurrent intravascular haemolysis (RBC lysis)
