B & I - Innate Immunity Flashcards
what does innate immunity entail
recognition of traits shared by broad ranges of pathogens, using a small set of receptors
is innate immunity slow or fast
innate immunity has rapid response
is innate immunity faster or slower than adaptive immunity
faster
what are the barrier defenses of innate immunity
skin, mucous membranes, secretions
what are the internal defenses of innate immunity
phagocytic cells, natural killer cells, antimicrobial cells, inflammatory cells
what does the humoral system consist of
soluble factors such as antimicrobial peptides that directly kill bacteria and antibodies which are produced by B lymphocytes
what does cellular immunity consist of (think of cells)
myeloid cells (innate) or lymphoid cells (adaptive)
does the innate immune response change or strengthen over time
no
is your innate or adaptive immunity the immediate and first-line defense against an infection
innate immunity
what do all living things have
some ability to discriminate between self and non-self
which (innate or adaptive) is more primordial
innate
does innate response have memory
no - what you are born with is what you will always have
what does defence against viruses rely on
cellular immunity - need to be able to distinguish infected from normal cells
what type of pathogens are bacteria (extracellular or intracellular?)
mostly extracellular (live outside cells)
what does defense against bacteria rely on
innate mechanisms and phagocytosis
defence against complex multicellular organisms, such as protozoa and parasites, relies on (direct killing by ___________ __________ released by _____________ _______________ __________)
direct killing by chemical mediators released by special myeloid cells
what are the chemical mediators (and how are they released and give one example)
granules filled with cytotoxic chemicals; degranulation releases the toxic inflammatory chemicals such as histamine
what are the three interlinked processes of innate immunity in mammals
- Complement
- myeloid cells and phagocytosis (neutrophils and macrophages)
- pattern recognition receptors
describe complement step
opsonization of microbes by blood proteins and the production of anaphylatoxins that attract and activate phagocytes
describe phagocytosis step
engulfment of the microbe by phagocytes (neutrophils and macrophages) that destroy the organism
describe PRR step (basically what are PRR)
receptors found on many myeloid cells that recognize complex microbial molecular patterns
what are most bacteria distinguished by
the gram stain
describe the features of a gram-positive bacteria
gram-positive bacteria have a thick peptidoglycan cell wall as a defense
describe the features of a gram-negative bacteria
have a thin peptidoglycan layer surrounded by an outer membrane
how are gram-positive bacteria destroyed
requires phagocytosis
can gram-positive bacteria be killed directly by complement?
no
how are gram-negative bacteria destroyed
can often by lysed directly by complement membrane attack complex
what do beta-lactam antibiotics such as penicillin do
block peptidoglycan synthesis
the peptidoglycan wall is involved in antibiotics working because
antibiotics interrupt the synthesis of the bacterial wall
how do neutrophils find infections from the confines of a blood vessel
using neutrophil extravasation
what are the five steps of neutrophil extravasation
- activation
- tethering
- adhesion
- diapedesis
- chemotaxis
what is the definition of neutrophil extravasation?
neutrophil extravasation is the ability of neutrophils to identify the site of infection by recognizing endothelial cells on the inner wall of the capillary that is closest to the infection
describe activation step
chemokines from tissue injury or inflammation activate the local endothelial cells lining the inside of an adjacent capillary wall
describe tethering step
neutrophil tethers to the inside capillary wall
what is the tethering step mediated by
selectins upregulated on endothelial cells and slalyl Lewis X (sLe^x) - a carbohydrate antigen on neutrophils
describe adhesion step
strong binding between neutrophil integrins and ICAM-1 on the endothelium. neutrophil immobilizes and flattens
describe diapedesis step
neutrophil squeezes between endothelial cells into the interstitial space
describe chemotaxis step
neutrophil migrates along a chemical gradient to the site of infection
what happens when chemoattractants such as C5a is released
they radiate away from the bacteria and are sensed by the leading edge of the neutrophil
when neutrophils migrate up the chemoattractant gradient what do they do to actin filaments
polymerize actin filaments at their leading edge and de-polymerize those filaments at their trailing edge
name the complement receptors
CR1, CR2, CR3, CR4
what are these complement receptors (on neutrophils) and what do they do?
they are myeloid cell receptors that bind activated complement deposited on bacteria
what is the main neutrophil receptor and what does in bind to
CR1, binds to C3b
what initiates phagocytosis
cross-linking of the surface CRs
what is opsonization
the process of coating microbes with complement proteins to form complex complement convertases ready for phagocytosis
what are the three pathways of activation
classical, lectin and alternative
neutrophils and macrophages engulf _________ _______ but ignore ___-_________ ____
neutrophils and macrophages engulf opsonized bacteria but ignore non-opsonized cells
what are FcR
the receptors that recognize antibodies that have coated the surface of bacteria
what are IgG and IgM
antibodies that recognize various antigens - epitopes on the surface of bacteria. they bind and coat the bacteria in antibody
list the 7 steps of FcR (antibody) mediated phagocytosis
- antibody (IgM and IgG) bind to bacterial antigens
- exposes the antibody Fc region
- neutrophil FcR binds to multivalent Fc
- activates phagocytosis
- membrane invaginates forming a phagosome
- fuses with a lysosome to form a phagolysosome
- phagolysosome acidifies and superoxides kill the bacteria
what does the C1 component of complement bind
the back end of the bacteria - Fc receptors will also bind to the back end of the antibodies which initiates the same phagocytic engulfment
name the 5 steps of phagocytosis
ingestion, fusion, acidification, digestion and exocytosis
what happens in ingestion
bacterium is captured by receptors, membrane invaginates into a phagosome
what happens in fusion
the phagosome and lysosome fuse to form a phagolysosome
what happens in acidification
the phagolysosome acidifies with H+ pumped in
what happens in digestion
acidification activates protease and stimulates the production of superoxides such as H2O2 and HOCl which kill bacteria
what happens in exocytosis
expulsion of the digested microbe
what do PRRs do
bind complex molecules that are unique to microbes
What are PAMPs and what are they recognized by
pathogen-associated molecular patterns and they are unique to microbes and are recognized by a set of pattern recognition receptors
do PAMPs change much
no they are part of the innate immune system and thus are evolutionarily stable
what do PAMPs do
stimulate the power switch for the adaptive response
what is the best-known PRR
toll-like receptors (TLR)
what does activation of TLR stimulate
a strong innate response through an important inflammation pathway
what happens if you don’t have the inflammation pathway activated through TLR
you don’t get an effective response - it drives everything
what is the best example of a PAMP
LPS (lipopolysaccharide)
what is LPS
membrane component of all gram-negative bacteria
what is LPS recognized by
TLR4
what are TLRs responsible for
driving the innate response
what do tiny amounts of LPS induce
a very powerful innate response
LPS is a ______
pyrogen
what does LPS do when injected into the bloodstream
causes a fever
what is a pyrogen
something that induces a fever
does LPS need to be removed from anything that is injected into humans?
yes
what does release of LPS by gram-negative bacterial infections do
leads to life-threatening septic shock
LPS is used by PRR to
sense invasion
