The evolution of innate immunity Flashcards
What are the core concepts of immunity?
- to discriminate self from non-self
2. to kill or disable an infecting agent
What is innate immunity?
The non-specific immediate response once a pathogen has been detected. Typically defined with having no memory - this is challenged though
What are the different components of innate immunity?
Barriers: - physical (skin) - physiological (low pH, killing things before they get to your gut) Humoral: - pattern recognition receptors (PRRs) - opsonins (complement and antibodies) - anti microbial peptides (AMPs) - cytokines Cellular: - phagocytes - natural killer cells
What drives the evolution of immunity?
> constant evolutionary arms race
stay in the same place
strong selective pressure to find immunity against the pathogen, leading to the host developing some sort of pattern-triggered immunity, which leads to increased pressure being put on the bacteria, which then develops a mechanism to fight the defence.
What did having a huge variety of pathogens enable our ancestors to develop?
Our first ancestors needed to respond to everything and therefore needed:
- a broad spectrum
- non-specific barrier
How can immunity traits be developed?
Over time or introduced individually. Can be direct or convergent evolution
What is an ancient component of the innate immune system that is present in all living organisms?
Antimicrobial peptides
What are antimicrobial peptides (AMPs) and how do they work?
Small peptides that have a very broad spectrum. They use the slight difference in the charge in the membrane to recognise the difference from self & non-self. They have cationic and amphiphilic characteristics. Generally secreted by white blood cells & epithelial cells.
- Bacteria membranes are slightly more negative than ours
○ Once attached to the membrane, a pore will be formed (hole punch mechanism)
○ A leak of the cell will occur
○ Cell will DIE
How did antimicrobial peptides (AMP) evolve?
Through convergent evolution throughout the lineages
Name examples of AMPs.
cathelicidin subfamily; LL-37, BMAP-27
defensin subfamily; α-defensin 4, β-defensin 2
What is the most ancient pathogen recognition system?
Toll-like receptors (TLRs) & NOD-like receptors (NLRs).
What are toll-like receptors (TLRs)?
- proteins that recognise pathogen associated molecular patterns (PAMPs)
- can be extracellular or intracellular (can be patrolling in membranes or outward facing)
- recognises all pathogens
- induce inflammation via NF-kappaB
What are NOD-like receptors (NLRs)?
- proteins that recognise bacterial peptidoglycan (or Strep, stays in the bacterial pathogens)
- solely intracellular
Where can TLRs & NLRs be found in the TREE?
All eukaryotes
What are PAMPs?
Pathogen associated molecular patterns
- molecular structure that is pathogen specific and not found in our cells
- e.g. bacterial lipopolysaccharide (LPS) (a diverse set of microbial molecules that share a number of different general “patterns,”)
- e.g. flagellin found in bacterial flagella, porins in the outer membrane of the Gram-negative cell wall
What are DAMPs?
Damage associated molecular patterns (DAMPs)
- endogenous danger molecules that are released from damaged/ dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs)
- e.g. heat-shock proteins;
altered membrane phospholipids
How do TLRs and NLRs work together to form an apoptotic response?
Inducing inflammation via NF-kappaB response
- recruits other parts of the immune system
- initiates the immune response
How is nucleic acid recognition useful in the innate immune system?
recognises foreign nucleic acids therefore can differentiate between self and non-self
What nucleic acid recognition mechanism does Bacteria & Archae have?
Through the driving force of being attacked by phages, the memory allows bacteria and archae to evolve to having: >CRISPR Archae has an enzyme called > Argonaute - Archae does not have a full RNAi mechanism, but has the major enzyme Argonaute that does the cutting/ splicing > Restriction enzymes - comes from bacteria - self vs non self - recognises invading phage
What nucleic acid recognition mechanism do Eukaryotes have?
> RNAi
- recognises foreign nucleic acids
- has been adapted in research for knockdowns (not knock outs)
How have nucleic acid recognition mechanisms evolved?
Through convergent evolution
Where is the complement system in the evolutionary TREE?
present in most animals
- difficult to pinpoint where it first appeared
What is the complement system?
part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation and attack the pathogen’s cell membrane.
- large no. of distinct plasma proteins that react with each other to opsonise pathogens and activate an inflammatory response
- circulate in the blood as inactive precursors - stimulated by one of several triggers, proteases in the system cleave and activate the cascade
Where are reactive oxygen species (ROS) in the evolutionary TREE?
All eukaryotes
- Archae can protect itself from ROS but there is no evidence that it produces it itself
What are reactive oxygen species (ROS) ?
- highly reactive molecules
- variant species of superoxide (contains oxygen)
- a natural by-product of metabolic processes
- can by synthesised deliberately for as defensive molecules
○ Phagosome maturation
○ Killing the cargo - recent studies have shown that it functions as a second messenger of signal transduction
Where is phagocytosis in the evolutionary TREE?
In some eukaryotes (Protists and animals)
Why is phagocytosis not seen in plants or fungi?
Phagocytosis became an impossibility due to the cell wall
What is the common homologue of phagocytosis present between us and archae? Suggest a reason as to how this came about?
- common homologue of actin & Arp2/3
- When symbiosis was occurring, a simple ancestral cell had an actin cytoskeleton that wasn’t as regulated as it is now. The membrane could push forward. Randomly, a protrusion engulfed something from the extracellular matrix
○ engulfed bacterial
○ That became our mitochondria
Where is programmed cell death in the evolutionary TREE?
Restricted to multicellular eukaryotes
Why would a cell undergo programmed cell death?
selective suicide is used as an immunity mechanism to prevent disease spread
- hope that the pathogen dies with you
- origin is unclear
What can trigger apoptosis/ programmed cell death?
DAMPS, DNA damage, viral infection, mitochondrial signals, receptor activation
What is behavioural immunity?
individual organisms detect the potential presence of disease-causing parasites in their immediate environment, and engage in behaviours that prevent contact with it
- seen in ants and humans (such as ebola etc outbreak, common practice to isolate the patient to stop spreading)
- self-medication such as herbal treatment (limitation of symptoms by behaviour)
What are the major steps in the evolution of innate immunity? (Antisocial Trying Nuggets Caress Round Pink Burgers)
- antimicrobial peptides (AMPs)
- TLRs and NLRs
- Nucleic acid recognition
- complement system
- reactive oxygen species
- programmed cell death
- behavioural immunity
