Alberts Basic Knowledge Flashcards
How is the innate immune system activated?
The innate immune system is activated by the binding of PAMPs/MAMPs to receptors that can activate the innate immune response.
What are PAMPs/MAMPs?
PAMPs are pathogen-associated molecular patterns and MAMPs are microbial-associated molecular patterns. They can be recognised by receptors of the innate immune system. PAMPs and MAMPs are common to pathogens and microbes, but are absent or sequestered in the host.
How do bacteria defend themselves against viruses?
Bacteria defend themselves from viruses using intracellular proteins called restriction factors, which block viral propagation.
What is the first barrier for pathogens in vertebrates, and how does this barrier defend the host against pathogens?
The epithelial surfaces that form the skin and line the respiratory, digestive, urinary, and reproductive tracts. The epithelia provide both physical and chemical barriers to invasion of pathogens: tight junctions between epithelial cells bar entry between the cells (e.g. keratinised epithelial cells), and a variety of substances secreted by the cells discourage the attachment and entry of pathogens (e.g. sebaceous glands that secrete fatty acids and lactic acids which inhibit bacterial growth). Epithelial cells in all tissues, including those in plants and vertebrates, secrete antimicrobial molecules called defensins. Defensins are positively charged, amphipathic peptides that bind to and disrupt the membranes of many pathogens, including enveloped viruses, bacteria, fungi, and parasites. The epithelial cells that line internal organs such as the respiratory and digestive tract also secrete slimy mucus, which sticks to the epithelial surface and makes it difficult for pathogens to adhere. The beating of cilia on the surface of the epithelial cells lining the respiratory tract and the peristaltic action of the intestine also discourage the adherence of pathogens. Moreover, healthy skin and gut are inhabited by enormous numbers of harmless and often helpful commensal microbes, collectively called the normal flora, which compete for nutrients with pathogens; some also produce antimicrobial peptides that actively inhibit pathogens proliferation.
Which receptors recognise PAMPs?
Pattern recognition receptors (PRRs).
Where are PRRs located, and give an example of its function in that location.
PRRs can be transmembrane proteins and located on the surface of many types of host cells where they recognise extracellular pathogens. For example, on macrophages and neutrophils they can mediate the uptake of pathogens into phagosomes to destroy the pathogens. PRRs can also be located intracellularly, where they can detect intracellular pathogens such as viruses. These PRRs are either free in the cytosol or associated with the membranes of the endolysosomal system.
Which types of PRRs are present in mammals, where are they located, and what do they recognise?
Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs), and C-type lectin receptors (CLRs).
TLRs are transmembrane cell-surface receptors and recognise distinct ligands of various pathogens (e.g. TLR4 recognises LPS and TLR5 recognises flaggelin). NLRs are solely cytoplasmic and recognise a distinct set of bacterial molecules. RLRs are solely cytoplasmic and detect viral pathogens. CLRs are transmembrane cell-surface proteins and recognise carbohydrates on various microbes.
Name examples of important pro-inflammatory cytokines.
Tumour necrosis factor-a (TNFa), interferon-y (IFNy), a variety of chemokines, and various interleukins (e.g. IL1, IL6, IL12, and IL17).
What is the difference between macrophages and neutrophils?
Macrophages are long-lived phagocytes that reside in most vertebrate tissues. Macrophages are among the first cells to encounter invading microbes, whose PAMPs activate the macrophages to secrete pro-inflammatory signal molecules. Neutrophils are short-lived phagocytes that are abundant in blood, but are not present in healthy tissues. They are rapidly recruited to sites of infection by various attractive molecules, including chemokines secreted by activated macrophages and peptide fragments produced from cleaved, activated complement proteins. Recruited neutrophils contribute their own pro-inflammatory cytokines.
What happens if a pathogen is too large to be phagocytosed by phagocytic cells?
Instead of phagocytosing the pathogen, phagocytic cells like macrophages, neutrophils, and eosinophils will gather around the invader. They secrete defensins and other damaging agents and release the toxic products of the respiratory burst. This barrage is often sufficient to destroy the pathogen.
What does the complement system entail?
The complement systems consists of about thirty interacting soluble proteins that are mainly made continuously by the liver and are inactive until an infection or another trigger activates them. These proteins amplify and complement the action of antibodies made by B cells, but some are also secreted PRRs, which directly recognise PAMPs on microbes.
Which viral PAMPs can PRRs recognise? And by which PRRs are they recognised?
Elements of the viral genome like double-stranded RNA (dsRNA), which is recognised by TLR3, and CpG motifs that are recognised by TLR9.
What happens when mammalian PRRs sense viral dsRNA?
When mammalian PRRs sense viral dsRNA, they induce the host cell to produce and secrete two antiviral cytokines, the type 1 interferons interferon-a and interferon-b.
How do type 1 interferons function?
Type I interferons act in both an autocrine fashion on the infected cells that produced it and a paracrine fashion on uninfected neighbours. They bind to a common cell-surface receptor, which activates the JAK-STAT intracellular signalling pathway to stimulate specific gene transcription and thereby the production of more than 300 proteins, including many cytokines.
How do type 1 interferons block viral replication?
They activate a latent ribonuclease that non-specifically degrades single-stranded RNA. They also indirectly activate a protein kinase that phosphorylates and inactivates the protein synthesis in the infected host cell. If these measures fail, the cell undergoes apoptosis to prevent viral replication.
