Innate Immunity 2 Flashcards
What cells can carry out phagocytosis?
Neutrophils and Macrophages
What are the innate immune cells?
Neutrophils
Macrophages
Dendritic cells
Natural Killer cells
What do cytokines do to blood vessels?
Dilate them, making them more permeable which allows immune cells to pass through
What is leukocyte extravasation?
The movement of leukocytes out of the circulatory system and towards the site of tissue damage / injury
What are examples of cell adhesion molecules?
ICAM-1 and ICAM-2
Where are cell adhesion molecules located and what do they bind to?
Found on the endothelium and they bind to interns on leukocytes
What are integrins?
Transmembrane proteins that are involved in the adhesion of cells to each other and also to their substrates.
What is phagocytosis?
The capture and digestion of foreign material
What are examples of opsonins?
Complement components (C3b)
Collectins (e.g. MBL)
Antibodies
What are examples of phagocytic receptors?
Complement receptors
Fc receptors
Mannose receptors
Scavenger receptors
What are the steps of receptor mediated phagocytosis?
1) Phagocytic receptor recognises a component of microbial surface and binds to the microorganism
2) Microorganism gets internalised by receptor-mediated endocytosis
3) Fusion of the endoscope with a lysosome forms a phagolysosome and the microorganism gets broken down
What are neutrophil extracellular traps (NETs) and how do they work?
A special form of cell death that some neutrophils can undergo when activated (NETosis)
During this, nuclear chromatin gets released by cells - trapping microorganisms and aiding phagocytosis
What do Pattern Recognition Receptors (PRRs) recognise?
Pathogen-Associated Molecular Patterns (PAMPs)
What are some examples of PRRs?
Toll-like receptors (TLRs)
NOD-like receptors
Rig-I like receptors (RLRs)
Cystosolic DNA sensors (CDS)
What does DAMPs stand for and where are they released from?
Damage-assocaited molecular patterns
Released from necrotic cells
Due to the rapid evolution of microorganisms, what do PAMPs detect?
Highly conserved and essential components of microbes
E.g. cell wall structures and nucleic acids
What are the two sections of Toll-like receptors?
Extracellular side which has LRRs (Leucine-rich repeats) that are the site of pathogen binding
Cytosolic with a TIR-domain which is a conserved stretch of roughly 200 amino acids
How are TLRs able to form heterosexual/homodimers?
TLR-1 and TLR-2 have binding sites for lipid side chains of triacyl lipopeptides.
Binding of each TLR to the same lipopeptide then induces dimerisation.
Where can TLRs be found?
Cell surface and endosome surface
Which TLRs are found on the cell surface and which TLRs are found on the endosome surface?
Cell surface = TLR 1, 2, 4, 5 and 6
Endosomal = TLR 3, 7, 8, 9, 1o
What type of microorganism’s products do TLRs detect?
Cell surface = Bacterial
Endosomal = Viral
How is TLR signalling able to aid host defence?
Induces genes involved in host defence (e.g. chemokines and antimicrobial peptides)
What is Waldenstrom macroglobulinemia?
A rare type of non-Hodgkin lymphoma caused by a MyD88 (protein) gain of function mutation.
B cells make large amounts of IgM which can cause excessive bleeding, vision problems and headaches.
Lymphoma cells proliferating in the bone marrow can cause anaemia, neutropenia and thrombocytopenia.
What are Nod-like receptors?
Cytoplasmic PRR molecules and they are nucleotide-binding leucine rich (NLR)
What do the Leucine-rich domains of nod-like receptors bind to?
Peptidoglycan which is present on the cell membrane of most bacteria
What is is the difference between NOD1 and NOD2?
They detect similar, yet distinct, peptides of peptidoglycan.
NOD1 binds to y-glutamyl diaminopimelic acid (mainly gram -ve bacteria)
NOD2 binds to muramyl dipeptide (both gram +ve and -ve bacteria)
What is a NOD2 gain of function mutation associated with?
Early onset of sarcoidosis
What is a NOD2 loss of function mutation associated with?
Susceptibility to Crohn’s disease
What are the two main groups of Nod-like receptors?
NLRCs (C = Caspase recruitment domain)
NLRPs (P = Pyrin domain)
What can activate NLRP3?
- K+ efflux
- ATP
- Reactive oxygen species (ROS)
- Lysosomal damage
What is the inflammasome (formed by NLRP3) essential for the secretion of?
IL-1 and IL-18
Activates them by cleaving their pro-forms
What is a gain of function mutation in NLRP3 called?
Cryopyrin-Associated Periodic Syndromes (CAPS)
What are the two types of Cryopyrin-Associate Periodic Syndromes (CAPS)?
Muckle Wells Syndrome: Can occur spontaneously or be triggered by cold, heat, fatigue or other stresses.
Familial cold auto inflammatory syndrome: Very rare and is triggered by exposure to cold.
What are some of the symptoms of Muckle wells syndrome?
Fever
Rash
Conjunctivitis
Sensorineural deafness
What are some of the symptoms of familial cold auto inflammatory syndrome?
Fever
Urticarial rash
Arthralgia (pain in joint)
Headache
How can both CAPS be treated?
With anakinra (IL-1RA)
What is the cause of CAPS?
Mutation in exon 3 of the NLRP3 gene, which leads to the overproduction of IL-1
What do RIG-I receptors bind to?
Cytoplasmic RNA
What do RIG-I receptors induce?
Pro-inflammatory cytokines and interferons (IFN)
What type of RNA do RIG-I receptors bind to?
Single stranded RNA that contains 5’-triphosphate
What are the stages of the acute phase response?
1) Cytokines (e.g. TNF, IL-6 or IL-1) induce the response during infection and/or inflammation
2) This induces opsonisation and phagocytosis
3) Can activate the complement pathways and it also raises erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
Where are acute phase proteins mainly produced?
The liver
