Microbial recognition and responses in innate immunity Flashcards
Define pathogen-associated molecular patterns (PAMPs)
Pathogen-associated molecular patterns (PAMPs): molecules that are common on pathogens (such as viruses and bacteria) but not expressed in vertebrate cells
What PAMPs do gram-negative bacteria express?
Gram-negative bacteria
LPS:
Have liposaccharide on their cell wall- made out of lipid and carbohydrate chains
Flagellin:
Have flagella containing protein called flagellin: this is what makes the bacteria swim
What PAMPs do gram-positive bacteria express?
Peptidoglycan
Have cell wall component called peptidoglycan
Flagellin:
Teichoic Acid
What are the PAMP types for viruses
Nucleic acids
Single stranded RNA
Double stranded RNA
Double stranded DNA
What is a Pattern Recognition Receptor and what does it do?
Pattern recognition receptors (PRRs): Receptors that bind to PAMPs and activate an immune response. PRRs are a key component of the innate immune system
Receptors of the innate immune system (PPRs) are encoded by inherited genes and recognize common molecular patterns typically expressed on microbes but not our own cells
What is the role of PRRs in the innate immune system?
Microbes contain and release PAMPs-> PAMPs activate pattern recognition receptors-> PRRs signal to release cytokines such as type I IFNs, IL-1 and TNFalpha
What are Toll-Like Receptors?
Toll-like receptors (TLRs): A group of structurally related receptors that bind to and recognize different PAMPs
What are the two locations of toll-like receptors in a cell, and what does each type do?
Cell surface TLRs are present on cell surface and will recognize flagellin, LPS…
Will lead to inflammation and formation of pus
Endosomal TLRs respond to nucleic acid- they will cause anti-viral state
How does the antiviral state happen?
1.Virus infects a cell
2. Infected cell secretes type I interferon
3. Sentinel cell called plasmacytoid dendritic cell also secretes Type I interferons in response to virus which bathes infected cells in type I interferons
-These type I interferons bind to the receptors of infected cells
4.Type I interferon binding induces cells to enter antiviral state and offers neighbouring cells protection against virus
-Type I interferon signaling induces production of protective protein inside cells
——This protein is innocuous for healthy cells and only has an effect on infected cells
————This is because in infected cells, there is synthesis of double stranded RNA, which is an obligate intermediate during viral biogenesis
——This protein binds to the viral double stranded RNA-> causes cells to either undergo apoptosis and die, leaving regeneration to the healthy cells in the tissue
What does the antiviral state increase expression of?
-Leads to increased expression of a protein that binds to dsRNA and activates further anti-viral signalling
-Leads to increased expression of apoptosis genes
-Leads to increased expression of an RNase that can degrade some viral RNAs
Summarize the antibacterial innate immunity signalling process from TLR
Signals for antibacterial innate immunity- Toll-like receptors activate NF-kB to induce the transcription of proinflammatory cytokine genes
-Cell surface toll-like receptor binds to a PAMP and dimerizes
-Sends signals into cell that allows transcription factor to migrate into the nucleus, bind to the promoters of these genes and induce expression of proinflammatory cytokines like TNF and IL-1
—–In cytosol, protein complex called NF-kB that travels into the nucleus and induces transcription of those proinflammatory factors by binding to promoters-> leads to cytokine production and inflammation/pus formation
—–NF-kB is usually inhibited by inhibitor in resting cells- TLR signalling causes this inhibitor protein to be degraded so that NK-kB can perform its function
Summarize antiviral innate immunity signalling process from TLR
Signals for antiviral innate immunity- Endosomal TLRs activate the pathway to induce type I interferon secretion and the antiviral state
—Endosomal toll-like receptor binds to nucleic acid PAMP
—Nucleic acid ligates the endosomal TLR which sends signals to induces phosphorylation of cytoplasmic transcription factor
—Transcription factor goes into nucleus to induce transcription of type I interferon genes and leads to type I interferons to be secreted-> induces antiviral state
What is complement and what does it generally involve?
Complement is a cascade of events that lead to inflammation and activates processes that can kill microbes (largely bacteria)
—–Many (but not all) steps in complement activation involve the cleavage of complement proteins into fragments
—–Cleaved fragments of complement proteins usually have some activity: for example, a fragment may form an active enzyme that can cleave other proteins. Some fragments can binding to microbes or initiate inflammation
What are the 3 initial complement pathways?
–Alternative pathway (spontaneous)
——Microbial surface activates complement spontaneously
——The surfaces of self cells have factors that inhibit C3b function-> in contrast, C3b remains active on microbial surfaces which leads to activation of downstream events in the complement pathway
–Classical pathway (antibodies)
——C1q binds antibody on microbe
–Lectin pathway (agglutinin)
——Agglutinin binds microbe
How does the complement pathway work after it has been activated?
Whatever the activation pathway (alternative, classical or lectin), when C3 is cleaved into C3b and C3a, there is a common pathway where in all cases the same mechanism is used to cleave C5 into C5b and C5a
The enzyme that does this is C5 Convertase
Once C5 is cleaved, C5b can help set up a C9 Pore
The C9 Pore is called the membrane attack complex (MAC)
What do all complement activation events converge on?
All complement activation events converge on the cleavage of a protein called C3 into 2 fragments: C3a and C3b
