Innate Recognition Flashcards
(26 cards)
What 2 ways can innate antigen recognition occur?
1) Direct recognition
2) Indirect/Opsonic recognition
What is direct recognition?
Entails special receptors recognising conserved patterns
What is indirect/opsonic recognition?
1) Involves engagement of specific receptors on surface of phagocytic cells with opsonins - molecules mark pathogens for phagocytosis
2) Opsonins includes IgG, IgE and compliments proteins C3b and iC3b
What is the role of Fc receptors (FcyRIIa) in opsonization?
1) Present on surface of phagocytic cells (macrophages, neutrophils and monocytes)
2) Bind to Fc region of antibodies (IgG and IgE) attached to surface of pathogens, facilitating recognition and phagocytosis of antibody-coated microbes
What is the role of complement receptors in opsonization?
1) Particularly CR1 (CD35), CR3 (CD11b/CD18), CR4 (CD11c/CD18) expressed on phagocytic cells
2) Interact with complement proteins (C3b and iC3b) that have opsonized pathogens, promoting attachment and ingestion of opsonised microbes
What are pathogen associated molecular patterns (PAMPs)?
1) Unique patterns present in microbes (microbial signatures)
2) Common to some groups of microbes (bacteria, fungi, viruses and parasites)
3) Absent in humans
4) Crucial for survival thus coded by conserved regions of gene
5) Also recognise endogenous danger molecules released from damaged/dying cells Damage-Associated Molecular Patterns (DAMPs) e.g., ATP
What is the role of DAMPs?
1) Activate immune system by interacting with PRRs
2) Contribute to host’s defense
3) Promote pathological inflammatory responses
4) Examples - S100 proteins, heat shock proteins (HSPs), ATP, HMGBI
What are some examples of PAMPs?
1) Lipopolysaccharide 9LPS) present on outer membrane of Gram-negative bacteria
2) Lipoteichoic acid and peptidoglycan in cell wall of Gram-positive bacteria
3) Flagellin in bacterial flagella
4) ssRNA and ssDNA of viruses
5) Bacterial DNA
6) Viral capsid/proteins
How are PAMPs recognised?
1) Recognised by PRRs
2) Receptors are expressed on plasma membrane of cells such as macrophages, neutrophils, dendritic cells and cellular compartments such as endosomes, lysosomes and cytosols
What are expressed PRRs expressed by?
1) Dendritic cells
2) Macrophages
3) Monocytes
4) Neutrophils
5) Epithelial cells
What are the expression patterns of PRRs?
1) Human neutrophils express TLR1-TLR9 (except TLR3 - for viral recognition)
2) Mast cells lining mucosa and vascular endothelium express TLR1, 2, 4 and 6
3) Monocytes express broad range of TLRs
What are the classifications of PRRs based on locations?
1) Membrane bound - receptor kinases, toll like receptors, C-type lectin receptor
2) Cytoplasmic sensors - NOD like receptors, RIG-1-like receptors
3) Inflammasomes - Multiprotein complexes that help in detection of PAMPs/DAMPs
What types of PRRs are there?
1) TLRs - Toll like receptors
2) CLRs - C-type lectin receptors
3) RLRs - RIGs-like receptors
4) NLRs - NOD-like receptors
What is the role of PRR P2X7 recognising DAMPs?
1) P2X purinoceptor 7 - member of P2X receptor family
2) P2X receptors are ion channels activated by binding of extracellular adenosine triphosphate (ATP)
What is the role of PRR RAGE in recognising DAMPs?
1) RAGE - Receptor for Advanced Glycation End product
2) Multi-ligand cell surface receptor belonging to immunoglobulin superfamily
3) Plays significant role in various physiological + pathological processes
What do NLRs (NOD-like receptors) recognise?
1) Uric acid crystals
2) Mitochondrial DNA released during cellular damage
What do CLR (C-Type Lectin Receptors) recognise?
Endogenous signals from damaged cells
What do AIM2 (Absent in Melanoma 2) recognise?
Double-stranded DNA
What is the role of HMGB1 in DAMPs recognition?
1) Stands for High Mobility Group Box 1, a chromatin-associated non-histone protein
2) HMGB1 is released by cells during injury, inflammation and cell death
What are Toll-like receptors (TLRs)?
1) Associated with defense against bacteria, fungi and viral infections
2) Are membrane spanning proteins
3) Its ligand-binding pocket is ‘horseshoe-shaped’
What is the structure of TLRs?
1) Extracellular - leucine rich repeats, horse shoe shape, binds ligands
2) Intracellular - TIR domain, important for signal transduction
What structures can TLRs come in?
Dimers either….
1) Homodimer
2) Heterodimer
How are TLRs stimulated?
Microbial products lead to activation of signalling pathways that result in induction of antimicrobial genes and inflammatory cytokines
What do TLRs stimulate?
Dendritic cell maturation and results in induction of costimulatory molecules and increased Ag-presenting capacity
