Immuno 11: Innate Immunity Flashcards
Parasites are a group of disease-causing agents that include ____ and ____.
worms and protozoa
The tremendous diversity of pathogens has led the immune system to develop 2 critical features. They are:
- specific BCRs and TCRs of equal or greater diversity than pathogens
- wide range of distinct effector mechanisms to combat the pathogens
Pathogens that remain in extracellular locations are best combated by \_\_\_\_ immune responses (complement fixing and neutralizing Ab isotypes) and by \_\_\_\_.
humoral; phagocytosis
Pathogens that grow in the cytoplasm of cells (intracellularly) are cleared primarily by ____ and ____ cells.
CTLs and NK cells
Protection against pathogens that grow in vesicles of phagocytes (intracellularly) is mediated primarily by ____-mediated
activation of ____.
T cell-mediated
activation of macrophages
Direct methods of tissue damage include __________, whereas indirect mechanisms involve ________.
production of exotoxins and endotoxins, and direct cytopathicity of host cells; innate and acquired immune responses of the host
What is molecular mimicry?
indirect mechanism of tissue damage wherein pathogen elicits antibodies specific for host cell proteins
Cryptidins/defensins are ____ ____ produced by ____ cells (lining the small intestine) and by
____.
antibacterial peptides; Paneth cells and neutrophils
How do amphipathic peptides attack bacteria?
they insert into their outer envelope and disrupt their integrity
What prevents bacteria from colonizing in the stomach
acid and hydrolytic enzymes
What component of tears and saliva degrades bacterial cell walls?
lysozyme
What are the two main mechanisms by which normal flora are a defense against pathogens?
- they compete for attachment to epithelial cells, and nutrients
- they produce antibacterial proteins called colicins
If it’s true that complement component C3 is constantly activated at low level in the blood, how does it respond to an infection?
the rate of C3 cleavage increases in the vicinity of some pathogens; also when C3 is cleaved it is rapidly degraded unless a pathogen is present for it to bind to
Factor __ binds to the C3 convertase to stabilize it by preventing Factor __ from dampening the complement activation cascade.
Factor P (properdin); Factor H
Please name the host cell surface proteins that prevent the complement cascade from marking them for uptake and destruction.
- CR1
- DAF
- MCP
What host cell surface proteins interfered with MAC formation on host cells?
CD59 (protectin)
Is factor H a plasma protein or a cell surface protein? What does it do?
plasma protein; it renders C3 convertase susceptible to cleavage by factor I in the process of protecting host cells from complement destruction
What 2 cells initiate the inflammatory response and provide innate cell-mediated immunity (CMI)?
macrophages and neutrophils
Macrophages and neutrophils have what 2 receptors on their surface that allow them to recognize/phagocytose bacterial material?
- PRRs - recognize PAMPs
2. complement receptors - recognize opsonized material
Once pathogens are ingested, what agents do macrophages/neutrophils produce to kill or deactivate the pathogen?
- acid
- toxic oxygen derivatives
- antibacterial peptides/proteins
- competitors
Big duties of macrophages include releasing ____, ____, and to act as ____.
cytokines, phagocytosis, professional APCs
What is considered the first of a series of reactions known as the imflammatory response?
arrival of neutrophils at the site
Neutrophils are specialized for working under ____ conditions.
anaerobic
How long do neutrophils survive after entering inflamed tissue, and what happens to their dead cell body?
they survive about 5-6hrs; the dead cells form pus
True or false: the neutrophil’s granules are formed upon phagocytosis of a pathogen.
False - they are pre-formed and ready to fuse with the phagosome
What are the contents of a neutrophil granule?
hydrolytic degradative enzymes, NADPH-dependent oxidases, and antimicrobial peptides (defensins)
What do NADPH-dependent oxidases generate?
they generate toxic oxygen radicals (superoxide, hydroxyl oxide, and hydrogen peroxide), which give rise to hypochlorous acid (HOCl)
What is the respiratory/oxidative burst?
this is the oxidative attack (production of toxic oxygen radicals) mounted by neutrophils on pathogens; can kill Gram positive and negative bacteria, fungi, and some enveloped viruses
True or false: once neutrophils empty all their granules, they will make more.
False - once neutrophils empty all their granules, they die, hence their short lifespan and all the pus
True or false: once macrophages empty all their lysosomal contents, they will make more.
True - this is how macrophages can live so long
What is netosis?
it’s the process by which neutrophils die while making a NET (neutrophil extracellular trap) that immobilizes pathogens; they expel their chromatin to form the NET and their antimicrobial molecules that attack pathogens caught in the NET
What are the 3 types of PRRs?
- endocytotic PRRs
- signaling PRRs
- secreted PRRs
True or false: endocytotic PRRs promote the attachment, engulfment, and destruction of pathogens by using intracellular signaling.
False - this is all done without intracellular signaling
What do endocytotic PRRs primarily recognize?
carbohydrates
Mannose receptors are an example of ____ PRRs and are present on ____.
endocytotic; macrophages
What kind of endocytotic PRR recognize charged ligands, and on what cells are they found?
scavenger receptors; found on all phagocytes
What is a glucan receptor?
an endocytotic PRR that is found on all phagocytes
Signaling PRRs include the large families of what two receptors?
- TLRs (toll-like receptors) - membrane bound
2. NOD-like receptors - cytoplasmic
TLRs recognize microbial constituents such as …?
LPS, CpG, DNA motifs, DS DNA, flagellin, proteoglycans
Once TLRs recognize their ligand, they initiate production of what?
cytokines - by way of several TLRs associating on the cell surface and initiating an intracellular signaling cascade to the nucleus
____ is the only TLR that is known to bind directly to its ligand, which is ____.
TLR-5; flagellin
Current understanding of NOD-like receptors is what?
these proteins have affinity for microbial products, and when they bind they initiate signaling in production of inflammatory cytokines
What are secreted PRRs?
PRRs that are secreted from host cells. DUH.
What are some examples of secreted PRRs?
MBL, complement receptors, collectins, serum amyloid, CRP, lipid transferases, and peptidoglycan recognition proteins (PGRs)
What pathogen surface groups does MBL recognize/bind?
sugar groups (predominantly), phospholipids, nucleic acids, and non-glycosylated proteins
Once MBL binds a pathogen, what happens next?
MASP-1 and -2 bind MBL
and these MASPs cleave C2 and C4; the products go on in the lectin complement pathway
C-reactive protein (CRP) binds to ____ on pathogens and then becomes a ligand for ___.
phospholipids; C1q
MBL and CRP are both what type of PRR?
secreted PRRs
What is the timeline for immune response to infection?
- innate - 0-4hrs after encounter
- early adaptive - 4-96hrs; will respond if the innate system is overwhelmed/evaded
3.
True or False: early adaptive responses involve recognition mechanisms that are based on relatively invariant receptors and do
not lead to lasting protective immunity.
True
What is the usual role of the early adaptive immune response?
to hold the bacterial infection in check until adaptive immune responses have formed
An important function of the innate immune response is to recruit more ____ and ____ ____ to the site of infection.
phagocytes; effector molecules
____ release a variety of molecules that are involved in the inflammatory response.
phagocytes
Inflammatory responses are characterized by ____, ____, ____, and ____.
pain, redness, heat, and swelling
TNF-α (produced by phagocytes) indirectly induces ____ in the small local vessels (in area of inflammation); this occludes the vessels, thereby preventing flow of blood; this helps to ____ of the pathogen through the bloodstream.
blood clotting; prevent dissemination to other regions of the body
TLR__/TLR__ heterodimers recognize lipoteichoic acid (‘LTA’, a component that is common to gram-positive bacteria) and zymosan (a component of fungi).
TLR2/TLR6
(Aid: 2 and 6 are 2 different “guys”, so two “lines” in Gram +, or they recognize 2 different guys: Gram+ bacteria and fungi)
True or False: TLR5 bind to double-stranded viral RNA.
False - it’s TLR3
Aid: thREE - R = RNA, EE = double stranded, “three” = TLR 3
TLR4 homodimers serve as a receptor for ____.
LPS (lipopolysaccharide, a component found on gram-negative bacteria)
(Aid: 4 and 4 are the same “guys”, so one “line” in Gram -)
Which TLR(s) recognize single-stranded viral RNAs?
TLR7 and TLR8
Aid: they don’t dimerize, they’re single-strands
What are the major end products of the acute phase response?
- liver secretes PRRs (MBL/CRP) to activate complement and opsonize pathogens
- recruitment and activation of phagocytes
- fever
What are the 3 cytokines most responsible for initiating the acute phase response?
IL-1, IL-6, TNF-alpha
How does sepsis lead to organ failure?
when a bacterial infection becomes septic, TNF-alpha is secreted systemically; this still has the effect of activating platelet adhesion, which can cause small vessels to occlude/collapse; this is particularly problematic in some organs, because it can cause them to fail/septic shock/death
Problems fighting a Gram-positive bug could be attributed to deficiency of which TLR(s)?
TLR2/6
Problems fighting a Gram-negative bug could be attributed to deficiency of which TLR(s)?
TLR 4
Which TLR(s) would be effective against parasites? (because they recognize GPI)
TLR1/2 heterodimer
The TLR1/2 heterodimer will bind ____ and ____.
lipopeptides (component of bacteria) and GPI (component of parasites)
TLR9 binds ____ in ____ and ____.
unmethylated CpG-rich DNA in bacteria and viruses
