Part 2 Flashcards
what happens if anatomical barriers fail
an infection begins
second line activates
how long does the second line take to activate
4 to 96 hours
what happens if the second line fails
recruitment of effector cells, PAMPs is recognized, effectors activated, and inflammation.
Moves onto the third line.
how long does it take for the third line to activate
96+ hours
how long does the first line take to activate
0-4 hours
what is portal of entry
the preferred entry a pathogen takes in order to infect the host
how are most pathogens contracted
through the mouth and respiratory tract
what are the most common portals of entry
Mouth/respiratory tract, GI tract, reproductive tract/other, external surface, wounds/abrasions, insect bites.
what are the features that allow pathogens to evade and penetrate
Capsules around the cell wall, usually a sugar layer (anthrax).
Specialized cell walls that allow pathogens to survive harsh environments.
Lysogenic convergence: change outer appearance so IS doesn’t recognize pathogens later.
what kind of cell walls do Gram positive bacteria have
thick cell walls
what does being Gram positive do for the bacteria
allows it to survive in harsh conditions
what do GPs secrete
exotoxins and endotoxins
examples of GP exotoxins
A-B exotoxins; superantigens (mounts a super strong immune response; so much so that it can kill you).
examples of GP endotoxins
Streptokinase: anti-coagulant
Collagenase: swims through your skin; breaks connective tissue apart (Flesh-eating bacteria).
what features do Gram negative bacteria have
a cell membrane, then a thin cell wall, then an outer membrane.
what do GN bacteria secrete
endotoxins
examples of GN endotoxins
LPS.
LPS is attached to the outer membrane.
Outer membrane is covered in LPS.
LPS acts like an extra layer of protection.
what are the four locations of pathogens
Interstitial spaces, blood, and lymph
epithelial surfaces
cytoplasm
vesicles
what are the extracellular locations
Interstitial spaces, blood, and lymph
epithelial surfaces
what are the intracellular locations
cytoplasm
vesicles
examples of pathogens found in the Interstitial spaces, blood, and lymph
Viruses, bacteria, protozoa, fungi, worms.
what is the protective immunity of interstitial spaces, blood, and lymph
complement, phagocytosis, antibodies.
examples of pathogens found on epithelial surfaces
Worms, gonorrhea, helicobacter pylori
protective immunity of epithelial surfaces
Antimicrobial proteins, antibodies (especially IgA)
IgA is found in all secretions: sweat, mucus
IgG is found in blood
pathogens found in cytoplasm
Viruses, chlamydia, protozoa
protective immunity of the cytoplasm
NKs and cytotoxic T cells (96 days to be fully activated)
pathogens found in vesicles
plague, legionnaire’s
Prefer to be in vesicles to evade immune responses.
protective immunity of vesicles
T cell and NK dependent macrophage activation.
what does inflammation depend on
depends on severity (# of damaged cells)
what is the second line’s intracellular defense mechanism
NK cells
what is the second line’s extracellular defense mechanism
phagocytic cells
what is the third line’s intracellular defense mechanism
CD8 cytotoxic T cells
what is the third line’s extracellular defense mechanism
antibodies from the B cells
what does the third line need for both intra and extracellular defense
Both require CD4 helper T cells to be activated.
what does the Skin, gut, lungs, eyes/nose/oral cavity all have
tight junctions
what are tight junctions
proteins that seal the areas between cells.
what are desmosomes
like buttons with fibers that anchor cells together.
what are gap junctions
openings between the cells, so that cells can share whatever goes through.
what does fungus like in the first defense? what pathogen does it attract?
Fungus likes keratin (athletes foot).
what is the mechanical washing of skin and gut
longitudinal flow of air and fluid
what is the mechanical washing of lungs
movement of mucus by cilia.
Goblet cells
what is the mechanical washing of eyes, nose, mouth
tears, nasal cilia.
what chemicals are in the skin
fatty acids, B-defensins, lamellar bodies, cathelicidin.
Sebum (fatty acid) prevents hair from becoming brittle.
Sebum is toxic, preventing bacteria from getting in pores/hair follicle.
what chemicals are in the gut
low pH, enzymes (pepsin), A-defensins, RegIII, cathelicidin.
what is in the crypt of gut cells
A-def and RegIII extremely acidic.
C-type lectins (proteins that bind sugars): RegIII
A-def is amphipathic protein
chemicals in the lungs
pulm surfactant, A-def, caths.
chemicals in eyes, nose, mouth
enzymes in tears and saliva (lysozyme), histatins, B-defs.
what do all first line components have
a microbiota
Bacteria want same bacteria/environments.
how do NK cells kill
the directed release of lytic granules or by inducing death receptor-mediated apoptosis via the expression of Fas ligand or TRAIL.
what is Gram-positive’s thick cell wall is made out of
peptidoglycans (NAG and NAM)
how are NAG and NAM connected vertically
peptide bridges
what are the NAG and NAM peptide bridges called
B(1,4) glycosidic bond
what does lysozyme target
B (1, 4) glycosidic bonds
what does phospholipase A2 degrade
digests phospalipids
how do defensins degrade
attach to the membrane and create a pore.
what are the granules in granulocytes made of
filled with defensin proteins (A, B, T)
where are alpha defensins found
the primary granules
what charge are active defensins
Cationic is the active portion.
what are zymogens
proteins that must be cleaved in order to function.
what line are antimicrobial proteins found in
second line
where are complement proteins produced
liver
what are serine proteases
enzymes that cleave peptide bonds in proteins
what three complement proteins cause inflammation
C3a, C5a, and C5b
what does C3 get cleaved to
C3a and C3b
what is the order in which complement proteins are cleaved
C1 > C4 > C2, C3, C4-9
what are the four guiding principles of immuno
recognition, effector function, regulation, memory
what do all complement pathways converge to
C3
what are effector functions
the function of each immunological component
an essential link between innate and adaptive immunity.
what are the effector functions of complement proteins
Recruit phagocytic cells to infection sites and promote inflammation.
Opsonization to trigger phagocytosis (This is most important)
Apoptosis
what is avidity in immuno
overall binding strength
what is special about mannose
is has specific patterns
what is affinity in immuno
the strength of bonding at one specific site
what is the lectin
any protein that binds to sugars.
how many lectin pathways are there
4
what are the four lectin paths
MBL
Ficolin (M, L, H)
what does mbl recognize
NAG
Mannose
Fucose
characteristics of the mbl monomer
3 monomers come together to form a monomer.
Trimeric clusters
A total of 18 binding sites.
what does mbl have high avidity to
mannose and fucose residues (MASP-2 and MASP-1)
how is ficolin different from mbl
Different carb-binding domain.
what does ficolin recognize
NAG (Gram negative and positive)
Teichoic acids (Gram positives)
what does ficolin bind to
oligosaccharides containing acetylated sugars.
what is the first step of lectin pathway
Activated MASP 2 (MBL or ficolin) cleaves C4 to C4a (weak trigger of inflammation) and C4b, which binds to the microbial surface.
second step of lectin pathway
C4b then binds C2, which is cleaved by MASP 2, to C2a and C2b, forming the C4b2a complex.
what is a C3 convertase
anything that has the potential to cleave C3 to C3a and b.
example of C3 convertase in Lectin pathway
C4b2a
third step of lectin pathway
C4b2a cleaves C3 to C3a and b, which binds to the microbial surface or to the convertase itself.
fourth step of lectin
One molecule of C4b2a can cleave up to 1000 molecules of C3 to C3b. Many C3b molecules bind to the surface of the microbe.
where is the newly formed C3 protein bound to in step five
thioester bond
what is the downside of the thioester bond
Thioester is very reactive.
Water can react and turn off the bond to C3.
step six of lectin path
Cleavage of C3 releases C3a, and a change in conformation of C3b allows the thioester bond to react with a chemical group on the pathogen surface.
final step of lectin pathway
Thioester bonds on C3b/C4b create covalent bonds on the surface of cells/pathogens.
what are the two outcomes of the lectin pathway
can result in C3b binding to the pathogen surface
Or C3b is inactivated by hydrolysis (water binds to the thioester bond).
what proteins are in the classical pathway
C1, 2, 4 3
how many C1 proteins are there
C1q, r, and s
what classical protein is similar to MBL
C1q
what classical protein is similar to MASP2
C1s
which classical protein is a serine protease
C1s
what does C1s cleave to classical
C4 and C2
what does C4b do classical
binds to pathogen and opsonizes it
Binds C2 for cleavage by C1s
what does C4a do classical
peptide mediator for inflammation
what does C2a do classical
cleaves C3 and 5
what does C2b do classical
precursor to vasoactive C2 kinin
what does C3b do classical
many molecules of c3b bind to the pathogen and act as opsonizers.
unitiate amplification via alt pathway
binds c5 for cleavage by c2b
what does c3a do classical
peptide mediator for inflammation
what is the function of the alternative pathway
Makes sure classical and lectin are stronger reactions
what are the four main components of alt pathway
C3
factors b, d, p
first step of alt pathway
C3b deposited by classical or lectin pathway C3 convertase.
C3b binds factor B
Bound factor B is cleaved by plasma protease factor D into Ba and Bb.
second step of alt path
C3bBb (C3 convertase) cleaves many C3 to C3a and C3b.
third step of alt path
C3 undergoes spontaneous hydrolysis to C3(H2O), which binds to factor B allowing it to be cleaved by factor D to Ba and Bb.
C3(H2O)Bb complex (C3 convertase) cleaves C3 into C3a and b rapidly unless it binds to the cell surface.
Happens in your bloodstream as it isn’t attached to a cell.
fourth step of alt path
Factor B non covalently binds to C3b on the cell surface and is cleaved into Bb.
what is the strongest trigger of inflammation
C5a
which proteins impact blood vessels to increase vascular permeability and cell-adhesion molecules.
C3a, C5a, C4a
why is increased permeability of vessels important
allows increased fluid leakage from vessels and extravasation of immunoglobulin and complement molecules.
more migration of macros, PMN, and leukocytes
what cytokine triggers inflammation
TNF alpha and histamine
how are holes formed in the membrane for complement system
C5 convertase cleaves C5
Converts into C5a and C5b
To C6 to C7 to C8 to C9
C8 has a hydrophobic region, which can interact with the membrane
Wedges itself into the membrane.
C9 binds to polymerize into the MAC, which forms a hole in the membrane.
how is the complement system turned off
protectin (CD59)
How do the 3 pathways carry out effector functions
Complement receptors (CRs 1-7)
Macrophages have CRs
Bacterium is coated with C3b
When only C3b binds to CR1, bacteria is NOT phagocytosed.
C5a can activate to phagocytose via CR1.
