Lecture 3: Innate Immunity II Flashcards
What happens in the innate immune detection of non-self?
- Pathogen Associated Molecular Patterns (PAMP), which are common to many microbes, binds and is identified by the Germline-encoded Pattern Recognition Receptors (PRR) located in the innate immune cell.
- Activation of immune responses, such as inflammation
Examples of PAMPS that are essential microbial structures
- Bacterial Lipopolysaccharide- present on many bacteria.
- Glycoproteins- bacterial glycoproteins have terminal mannose residues, mammalian ones have terminal sialic acid or N-acetylgalactosamine
- Double-stranded RNA- common to many viruses
- Unmethylated CpG DNA- common to bacteria
Characteristics of PRR
- Detection of non-self structures
- Ubiquitous, either as a circulating molecule or through expression on innate immune cells
- Rapidly triggers potent antimicrobial responses
What is a PRR?
Innate immune receptors that detect conserved, essential microbial features.
Active PRRs drive )_________.
Inflammation
Inflammation
mobilization of immune cells to sites of infection
Toll-like receptors are major pattern recognition receptor family. Give an example
Toll knockout in fruit flies leads to uncontrolled infection by fungus
Toll-like receptors (TLRs) are ______ for PAMPs
PRRs
Each Toll-like receptor (TLR) has a distinct ______ and _____, and each initiates a particular ____________.
location and ligands
signaling pathway
How does PRRs differ in structure/function?
- some PRRs are Phagocytic receptors
- some PRRs are not Phagocytic receptors but stimulate the activation of immune cells.
Pathogens can change rapidly. Give an example of this
there are 30,000 known coronaviruses
What is the reason why there are many PRRs?
There are many types of pathogens and it is important to have a recognition system that can recognize any form of any pathogen. That’s why there’s so many PRRs.
Pathogens are disadvantaged by having small _____ and at least some _______(low variation) components: that are targets of PRRs
genomes, conserved
Where do PRRs reside?
cell surface
What do PRRs do or where do they function?
- function in endosomes
- surveil the cytoplasm
- surveil for intact PAMPs, degraded PAMPs, and PAMPs that are never outside of the cell
Where do PRRs get expressed?
PRRs are variously expressed on, or in all leukocytes and boundary cells (endothelium and epithelium), and especially in phagocytic cells.
Almost all TLR signaling leads to the production of ______ and/or _______, which are both transcription factors.
IRFs and or/ NF-κB
IRF
- interferon response factors
- anti-viral response
NF-κB
turns on many immune response gene
RIG-like receptors (RLRs) include ________ and ________ which are related cytoplasmic sensors of viruses.
RIG-I and MDA5
what do RLRs have in common (or similarity) with TLRs?
signaling pathways
RLR dependent signaling can amplify _____ signaling
TLR
Results of PRR signaling
- production of Type I interferon (IFN-I). IFN-I augments innate and adaptive immunity.
- production of various pro-inflammatory cytokines
- induces many other immune response genes
Importance of PRR Innate Immune Signaling
- Speed- TLR signaling is “on” within minutes of detecting microbial PAMP. Initial activation of adaptive immune responses requires days.
- Economy- A limited number of TLR (approx. 10 members in humans, fish have 22+) can detect large numbers of different pathogens.
- Amplification- A localized detection of microbes can result in activation of large, systemic responses.
Why are there so many types of, and redundancy in, pattern recognition?
- To overcome attempts by microbes to evade one or more PRRs.
- Having multiple PRRs that can detect different common features of the same microbe enhances the chance the microbe is detected.
- Cross-talk in signaling pathways induced by different PRRs allows for better control over the type or degree of response.
