Lecture 2 Flashcards
Who is Ilya Mechnikov?
Father of innate immunity
What was Mechnikov’s discovery?
first to demonstrate phagocytosis and usefulness of inflammation
how did Mechnikov demonstrate phagocytosis?
put mango thorn into translucent starfish larvae –> cells gathered around thorn, therefore cells must have purpose
how does Mechnikov’s experiment relate to what we know today?
mimics the neutrophil swarm during infection
what did Janeway theorize?
in order for phagocytes to attack, the innate immune cells must recognize components of microbes –> determine self vs non-self
how do innate immune cells distinguish self vs non-self?
PRRs on innate immune cells recognize microbial component, PAMPs, on microbes
2 examples of PAMPs
- dsRNA
- LPS
What is an immunologist’s “dirty little secret”? how does it work?
adjuvants –> dead mycobacterium and other components that were PAMPs that stimulate immune response
why is there a diverse set of PRRs?
to be able to detect many different microbe PAMPs
why do PRRs follow the idea of “form follows function”
location of receptor determines what PAMP it can detect and therefore downstream effector function
ex. receptors inside the cell bind viral PAMPs
ex. receptors outside the cell bind extracellular pathogen PAMPs
what is a limitation of Janeway’s PAMP hypothesis based on Metchnikov’s observation? significance?
the thorn is not a pathogen but the cells were still able to migrate –> therefore, maybe our immune response senses DAMAGE rather than pathogen/non-self
what is Matzinger’s Danger Theory?
innate immune cells detect danger via indicators of cell stress/dysfunction/death, not just detection of PAMPs
what is the term for things that trigger innate immune cells in the Danger theory?
DAMPs –> microbial and non-microbial inflammatory triggers
2 general types of inflammation inducers
exogenous and endogenous
2 types of exogenous DAMPs
microbial and non-microbial
4 types of endogenous DAMPs
- cell-derived
- tissue-derived
- plasma-derived
- ECM-derived
another name for some endogenous DAMPs?
ALARMINS –> alarm the innate immune cells to activate
4 core components of inflammation
- INDUCERS (stimulants)
- SENSORS (detectors)
- EFFECTORS (cell type)
- MEDIATORS (soluble factors)
what are the sensors in inflammation?
PRRs –> detect pathogens and damage
what are the effectors in inflammation?
basically every cell in our body is an immune cell according to the danger theory because all can detect stress
what are 5 mediators in inflammation?
- cytokines
- chemokines
- anti-microbial peptides
- Ab
- lipid mediators
why do we need mechanisms to control inflammation?
too much inflammation is bad!
what happens if inflammation causes too much tissue repair? (2)
- leads to fibrosis –> compromises elasticity of tissue so it cannot function properly
- excess collagen deposition allows tumour to grow bc immune system cannot interfere with tumour
what happens in chronic inflammation?
system gets so stressed –> leads to tissue malfunction bc body can only handle so much inflammation and stress –> leads to disease
generally, what is the goal of inflammation?
to return to a normal system
does inflammation ever reach homeostasis?
technically the process is continuous and ALWAYS occurring to resist change, just the level of inflammation varies
what did Metchnikoff determine?
the immune system evolved for tissue growth, NOT defense
how did the immune system evolve for tissue growth rather than defense?
the initial role of macrophages was EFFEROCYTOSIS –> remove dead cells
then macrophages evolved to undergo phagocytosis as defense
what do macrophages mediate?
macrophages mediate harmony and disharmony in the body and the level of pathological inflammation
what allows macrophages to mediate harmony and disharmony in the body?
macrophages are found in every tissue
describe tissue-resident macrophages
produced during development and stay in tissue forever –> non-migratory
3 general states of tissues
- homeostasis/regulated harmony
- physiological inflammation
- overt/pathological inflammation
what is the cell state during physiological inflammation?
stressed or malfunctioning
what is the cell state during overt/pathological inflammation?
damaged or infected or dead
describe normal tissue state and then what causes overt/pathological inflammation?
constantly changing (regulated harmony) normally, but signals can become imbalanced and cause overt/pathological inflammation
where does physiological inflammation occur?
just below epithelium
where does overt, protective inflamamtion occur?
within tissue
where does overt, damaging inflammation occur? what can this lead to?
in system circulation –> sepsis
hierarchy of inflammation
regulation relies on function which relies on structure
what are 3 factors that may determine severity of inflammatory response?
- amount of pathogen
- virulence of pathogen
- ability of pathogen to breach epithelium
how does Matzinger’s danger theory differ from Janeway’s self vs non-self concept?
danger theory is more broad –> doesn’t need self vs non-self discrimination
why are adjuvant’s known as immunologists’ “dirty little secret”?
they can stimulate the immune response
if we have immune cells resident to / surveying non-lymphoid organs, why do we need secondary lymphoid organs?
tissue-resident cells are typically innate and secondary lymphoid organs are typically adaptive
secondary lymphoid organs allow for activation of naive lymphocytes so they can proliferate and express certain adhesion molecules to be able to enter other organs
what are the disadvantages of being sensitive to PAMPs and DAMPs?
PAMPs and DAMPs are non-specific and we have less control over it –> can be activated by things we don’t want it to be activated by, like allergens
what allows macrophages to be quick and effective at controlling infection?
- macrophages already in tissues
- always phagocytosing and testing the waters
- have lots of PRRs
