Innate Immunity 1 Flashcards
what 2 types of surfaces does a pathogen enter through?
- mucosal
- epithelial
what allows a pathogen to cause infection?
pathogen must breach one of the barriers thru various routes of entry
why is human skin resistant to E. coli colonization despite exposure?
- nutrients, pH
- can’t breach
- skin can make antimicrobial protein against gram-neg
what are 4 examples of epithelial surfaces that are barriers?
- skin
- gut epithelium
- respiratory epithelium
- mucosal membranes
how do saliva, hair, mucous, and tears provide innate immunity?
contain molecules that are antimicrobial
what are 2 types of protective substances produced by the epithelial layers?
- acidic pH
- antimicrobial peptides
what are 4 cell types involved in innate immunity?
- neutrophils + other granulocytes
- monocytes/macrophages
- dendritic cells
- NK cells + other innate lymphoid cells (ILCs)
describe the different types of monocytes/macrophages
all have same function but different types based on tissue
what are the 2 types of mature dendritic cells?
- conventional DCs
- plasmacytoid DCs
what are 3 types of molecules involved in innate immunity?
- enzymes
- anti-microbial peptides
- complement
what is an example of an enzyme involved in innate immunity and its function?
lysozyme –> digests peptidoglycan of gram-pos bacteria
what is an example of an anti-microbial peptide involved in innate immunity and its function?
defensins –> disrupt the cell membrane
what is the definition of phagocytosis?
engulfument and internalization of pathogens/pathogen components upon binding to receptors on surface of phagocytes
what are the 3 types of phagocytes?
- macrophages
- granulocytes (neutrophils)
- immature DC
phagocytosis can lead to: (3)
- removal and killing of pathogen
- cleaning debris from killing pathogens
- production of antigenic peptides to present to T cells
what are the 2 types of phagocytes that produce antigenic peptides to present to T cells?
- DCs
- macrophages
how do phagocytes recognize pathogens?
by receptors, usually PRRs
do all PRRs induce phagocytosis? are all receptors involved in phagocytosis PRRs?
no
no
how does indirect phagocytosis occur?
phagocyte recognize opsonins on pathogen surface
what are opsonins?
soluble proteins that are bound to microbial surfaces
what is another name for opsonins?
soluble pattern-recognition patterns
what is the role of opsonins?
enhance phagocytosis
what is the enhancement of phagocytosis called?
opsonization
what is an example of an opsonin?
antibody
what are the 5 steps of phagocytosis?
- phagocytosis initiated by receptors interacting with microbes (PAMP)
- pseudopodia extend from the phagocytic cell
- pathogen is internalized in a phagosome
- phagosome fuses with 1+ lysosomes to make a phagolysosome and lysosomal contents are released
- phagolysosome acidifies and acquires antimicrobial peptides + enzymes to kill microbe
what is a phagosome?
large membrane-enclosed endocytic vesicle that internalizes pathogens
what allows for the acidification and production of antimicrobial peptides/enzymes?
the fusion of phagosome and lysosome
what is unique about neutrophil phagocytosis?
they contain primary and secondary granules in cytoplasm (INSTEAD OF LYSOSOMES) which fuse with phagosomes and produce antimicrobial peptides
what does the phagolysosome do to kill microbes? (4)
- produce antimicrobial proteins + peptides
- low pH
- hydrolytic enzymes
- oxidative attack
what are the 2 types of hydrolytic enzymes produced during phagocytosis?
- lysozyme
- proteases
what does oxidative attack do?
creates ROS to damage microbial membranes and intracellular components
why can phagocytes produce ROS?
phagocytes have a unique NADPH oxidase enzyme complex (phagosome NADPH oxidase)
what happens when ROS is produced by NADPH oxidase?
increased oxygen consumption –> respiratory burst
does the phagolysosome affect innate or adaptive immunity?
both!
what are the 3 roles of the phagolysosome in innate immunity?
- pathogen killing
- pathogen processing
- pathogen presentation to sensory cytosolic receptors
what are the 3 roles of the phagolysosome in adaptive immunity?
- antigen degeneration
- antigen processing
- antigen presentation
what happens to cells that have undergone apoptosis?
they are cleared by phagocytes
how are cells cleared once they die?
the dead/dying cells express DAMPs which signal for them to be eaten
what does DAMP stand for?
Damage-Associated Molecular Patterns
what is CD47?
expressed by healthy cells (most cell types) that signal for them NOT to be eaten
how does CD47 work?
CD47 binds SIRPalpha (signal regulatory protein alpha) on macrophages to INHIBIT PHAGOCYTOSIS
What type of cells express elevated levels of CD47?
tumour cells
where are macrophages located?
they are located at tissue
where are neutrophils located?
they are recruited to the site of infection
what is pus?
dead and dying neutrophils
what do neutrophils produce?
Neutrophil Extracellular Traps (NETs)
what percent of neutrophils produce NETs?
20-60%
what is the role of NETs? (2)
- traps microorganisms to prevent spread
- produce antimicrobial peptides/enzymes
what can granule enzymes in neutrophils do to microbes?
they enter the nucleus to modify histones so CHROMATIN DECONDENSES
what allows for the production of NETs?
once chromatin is decondensed, PM ruptures and cytoplasm/nucleoplasm are released to form NETs
what is the “macrophage of the brain”
microglia
what is the role of microglia?
establishing proper neuronal connections for brain development, memory, learning
what is multiple sclerosis?
inflammatory disease w myelin/neuron breakdown, causing toxic debris
how is toxic debris in MS removed?
by microglia and other macrophages (but this does not fix the missing neurons!)
in general, what are microglia required for?
CNS repair
what happens when the microglia receptor is KO?
cells cannot migrate to site of damage –> no phagocytosis
