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227 Cards in this Set

  • Front
  • Back
What are the 3 direct mechanisms of tissue damage by pathogens?
1. Exotoxin release
2. Endotoxin release
3. Direct cytopathic effect
what are the 3 indirect mechanisms of tissue damage by pathogens?
1. immune complexes
2. anti-host antibody
3. cell-mediated immunity
where are the 4 possilbe sites of infection?
1. interstitial spaces, blood lymph
2. epithelial surfaces
3. cytoplasmic areas
4. vesicular comparmtents
what provides innate immunity in interstitial spaces, blood and lymph? (3)
1. antibodies
2. compliment
3. phagocytosis
what provide innat immunity to epithelial surfaces? (2)
1. IgA antibodies
2. antimicorbial peptides
what provides innate immunity to cytoplasmic areas? (2)
1. Cytotoxic T cells
2. NK cells
what provides innate immunity to vesicular compartments?
activated macrophages
what are the 5 stages of infection?
1. Adherence to epithelium
2. Penetration of epithelium causing local infection
3. local infection triggers innate immunity
4. infection increases with lymphatic spread
5. adaptive immuniy develops
which T cells are involved in the innate response?
gamma/delta T cells
what are the 2 compliment pathways that are involved in innate immunity?
alternative and lectin (mannose binding) pathways
what is the role serpines and alpha2-macroglobulin?
inhibit potentially damaging proteases which microbial cells use for invasion and colonization of human tissues
what is the main defense against everyday invasions?
the mechanical barriers of epithelia and mucosa
what keep pathogens from going between the epithelial cells lining the entirety of the exposed body?
tight junctions
give 4 examples of chemical barriers?
1. Fatty acids on the skin
2. low ph of stomach
3. enzymes lick lysozyme and pepsin
4. antibacterial peptides such as crypidins
what makes it difficult for pathogens to stop and colonize epithelial cells?
their surfaces are washed by air, mucous, and fluids
where do the most immune responses occur?
in the MALT
why is giving antibiotics potentially very damaging to a patient?
it wipes out their normal gut flora allowing harmful pathogens to gain a foothold once repopulation occurs
what are the three types of soluble molecules associated with the innate immune response?
1. opsonins -alternative and lecting pathways of compliment
2. seroins and alpha2-microglobulin
3. Type I interferons
what are examples of type I interferons?
INF-alpha, INF-beta
what is the effect of alternative compliment pathway on microbial surfaces?
it tags the cells for phagocytosis
what is the function of properdin?
stabalizes C3 convertase on microbial surface
what two factors disrupt C3 convertase on microbial surfaces?
1. DAF decay accelerating factor
2. MCP membrane cofactor proteins
what is human serum loaded with to stop the serpins and alpha2-microglobulins?
protease inhibitors
how is serpin deactivated?
proteased cleave serpin and form covalent bond with cut pieces causing a deactivating confromation change
describe the inactivation of alpha2-microglobulin?
protease cleaves the bait region and cleaved alpha2-microglobulin surrounds and covalently binds protease
describe the 4 characteristics of the innate response?
1. raid response (occurs within hours of infection)
2. does not varry from infection to infection
3. limited specificity (repeating epitopes such as LPS or TLR-4)
4. is constant throughout the infection
what happens when compliment binds compliment receptor?
compliment activation followed by opsinization and eventually lysis
mannose containing microbial carbohydrates are recognized by which receptor?
mannose binding lectin (MLB)
what does MLB binding of mannose result in?
compliment activation leading to opsonization
what receptor recognizes phosphatidyl choline and pneumococcal polysaccharides on pathogen surface?
C-reactive protien (CRP)
what does CRP binding of phosphatidyl choline or pneumococcal polysaccharides cause to happen?
activation of compliment leding to opsonization
what is bound to a cell membrane by CD14, MD-2, and TLR4?
lipopolysaccharide (LPS) receptor
where is LPS found?
gram-negative bacterial cell walls
what purpose does LPS receptor serve?
allows cells of the innate immune system to recognize gram negative bacteria
what receptor binds microbial components not found on host cells?
toll-like receptor
what is the funcion fo toll-like receptor?
induces innate immunity
what binds bacterial cell wall components?
nucleotide-binding oligomerization domain (NOD) receptors
what is the function of NOD receptors?
activate innate immunity
which innate immune receptor has many targets including gram-positive, gram-negative, and apoptotic host cells?
scavenger receptors (SRs)
what do SRs initiate?
phagocytosis or endocytosis of bound gram-positive, gram-negative, and apoptotic host cells
what is a key recognition receptor found in dendritic cells, B cells, and macrophages?
Toll-like receptor
what type of molecules do toll-like receptors see? (page 356 notes)
external structures on fungi and bacteria like lipoproteins and internal structures like viral RNA and DNA
TLR1/TLR2 dimer recognizes what?
bacterial parasites
TLR2/TLR6 dimer recognizes what?
Gram-positive
TLR4/TLR4 dimer recognizes what?
Gram-negative
TLR5/TLR5 dimer recognizes what?
Flagellated bacteria
TLR3, TLR7, and TLR8 have what function?
recognize viral double-stranded DNA
TLR9 recognizes what?
bacterial DNA elements
what provides immediate recognition of microbial surface patterns?
pattern recognition receptors (PRRs)
describe the regulation of genes by Toll-like receptors
1. TLR binds ligan
2. TLR transmits signal to MyD88 which begins intracellular singaling pathway
3. at end of pathway NFcappaB and MAP kinases are activated and act as transcription facotrs for certain genes
what happens in X-linked recessive ectodermal dysplasia (EDA-ID)?
NFkB activation (IKK complex) doesn't happen and multiple innate and adaptive pathways are impaired leaving patient susceptible to pyogenic and intracellular pathogens
what are the manifestations of autosomal EDA-ID?
same as X-linked
what happens interleukin-1 receptor doesn't function?
IKK complex cannot form and therefor NFkB deficiency occurs
what are leucine rich, intracellular, protiens which are regulated by pro-inflammatory cytokines?
NOD1 and NOD2
what upregulates expression of NOD1?
IFN gamma alone
what upregulates NOD2 expression?
TNF-alpha, but is augmented by INF gamma
what do NOD1 and NOD2 recognize?
bacterial peptidoglycan(PGN)
NOD1 ligand is mostly found on what type of bacteria?
Gram-negative
NOD2 ligand is mostly found on what kind of bacteria?
Gram-positive and Gram-negative
what is the name of the NOD2 ligand?
muramyl dipeptide (MDP)
Where are all NOD receptors found?
all intracellular
describe the recognition of PGN as it applies to TLR and NOD?
TLR2 recognizes intact extracellular PGN whereas intracellular PGN is recognized by NOD2
what diseases are associated with NOD difficiency?
Crohns, inflammatory bowl disease, and asthma
what do G-coupled proteins cause to happen when chemokines bind to them?
cause cAMP levels to drop
what does a drop in cAMP in inflammatory cells cause to happen?
chemotaxis
what are the two groups of chemokines?
CC and CXC where C stands for cysteine residues and X for an alternative residue or tripeptide
what is the chemokine CCL4 important for?
it acts as an inhibitor of HIV
what are the pro-inflammatory cytokines? (3)
1. IL-1
2. TNF-alpha
3. IL-6
what is the cytokine made by NK and NKT cells that promotes production of TNF-alpha?
TNF-gamma
what is the receptor which is responsible for starting the biological cascade of inflammatory cytokine production?
Toll-like receptor
what is the intracellular trasncription factor that is activated by toll-like receptors and is responsible for inflammatory cytokine gene expression?
NFkB
what are the most important lipid mediated components (formed breakdown of phospholipids of self-cells)involved in the inflammatory response?
prostaglandin and leukotriene A-1 - synthesized from arachidonic acid via the cyclooxygenase and lipoxygenase pathways
prostaglandins are many involved with which inflammatory response?
vascular permeability
leukotrienes are many involved with what inflammatory response?
bronchial smooth muscle contraction
what are the 4 systems that interact when there is endothelial damage?
1. kinin system
2. clotting system
3. fibrinolytic system
4. compliment system
what is the first cell to give of the signal during a infection?
macrophage
what is the first cell to come to the site of damage or infection?
neutrophil
what allows neutrophils to attach to the endothelium of the blood vessels close to the site of infection? (2)
1. adressins
2. selectins
what is the main contributor to pus in an infection?
neutrophils
what stimulates bone marrow to release more neutrophils?
cytokines release by NK cells and macrophages at the site of an injury or infection
what is the second cell to arrive at a site of damage?
a macrophage from a monocyte which has moved into the damaged tissue
what is the purpose of the new macrophages coming into a site of infection or damage?
to mediate inflammation via pro-inflammatory cytokines
in a tissue that is not infected, how many neutrophils do you see?
few to none
compare the half-lives of neutrophils and macrophages?
macrophages live much longer
what is the only action of neutrophils?
neutrophils only are involved in phagocytosis
macrophages activated by INF-gamma produce what in their phagosomes?
nitric oxide
what generates oxygen-dependent radicals in macrophages phagosomes?
NADPH-dependent oxidase
what is the competative action of macrophages that destroy invading bacteria?
the absorb iron and B12 in the area so bacteria lack nutrients to grow
what tells a macrophages that bacteria are present and causes activation of the macrophage?
Toll-like receptors bind lipopolysaccharide
describe the entire series of events associated with binding of lipopolysaccharide with toll-like receptors?
1. LPS binds plasma-binding protein (PBP)
2. CD14 binds PBP bound LPS
3. CD14/LPS binds toll-like receptor 4
what does binding of LPS to toll-like receptor (TLR-4) cause to happen?
activation of NFkB and expression of inflammatory cytokines
what limits the effects of the oxygen radicals released by macrophages on our own tissues?
we have superoxide dismutase and catalase to destroy the radicals
what is the response mediated by IL-1? (4)
1. activates vascular endothelium
2. activates lymphocytes
3. causes local tissue destruction
4. increases access of effecotr cells
what is the ultimate consequence of IL-1 production?
fever and increased IL-6 production
what are the 4 responses mediated by TNF-alpha production?
1. activates vascular endothelium
2. increases vascular permeability
3. increases access of IgG, compliment and cells
4. increases lymph production
what is the ultimate consequence of TNF-alpha production?
fever, mobilization of metabolites, and if widespread, shock
what are the 2 responses mediated by IL-6?
1. lymphocyte activation
2. increased antibody production
what is the ultimate consequence of IL-6 production?
fever, acute-phase protein production by hepatocytes
what is the function of CXCL-8?
chemotactic factor which recruits neutrophils, basophils, and T cells to infection sites
what is the function of IL-12?
activates NK cells and induces differentiation of CD4 T cells into TH1 cells
what are all the cytokines released by macrophages in response to infection? (5)
1. IL-1
2. TNF-alpha
3. IL-6
4. CXCL-8
5. IL-12
what is the cytokine which is involved with activation of the compliment system?
IL-6
how is fever induced by cytokines?
go to hypothalmus and increase heat production, go to muscle and fat to increase energy metabolism to increase heat
what is the purpose of raising body temperature?
increases effectiveness of antibody binding and reduces the environment bacteria have to rapidly reproduce
what is the name of the disorder which is caused by a widespread coagulation of RBCs due to macrophage release of TNF-alpha?
disseminated intravascular coagulation (DIC)
what is the default macrophage?
M2
what is the macrophage that is classically described?
M1
M1 macrophages are stimulated by what cytokines produced by what cells?
IFN-gamma, produced by TH1 cells
M2 macrophages are stimulated by what cytokines produced by what cells?
IL-4, IL13, TGF-beta, produced by TH2 cells
what is the function of M2 macrophages?
anti-inflammation
what are the effector functions of M2 macrophages?
tissue remodeling and angiogenesis promotion
production of mannose binding lectin and C-reactive protein are mediated by which macrophage cytokine?
IL-6
which macrophage cytokine would result in compliment serum levels increasing?
IL-6
what enables neutrophils to arrest and undergo adhesion and eventually transendothelial migration?
integrins
migration of lymphocyte into selective tissues is known as?
trafficking or homing
what allows for induced diapedesis of leukocytes between endothelial cells after the adhere via integrings?
chemokines
how does the cytokine CXCL8 (a chemokine) allow for leukocytes to cross endothelial cells of blood vessels?
It tells the leukocyte where the site of injury is be sitting on the endothelial cell wall close to the injury site
what is the integrin involved in firm adhesion of leukocytes to vessel endothelium?
ICAM-1
mannose binding lectin is a member of what protien famile?
collectins
what does C-reactive protein bind to on bacteria and what is its function?
binds to phosphoyl choline and acts as a opsonizing agent
what is the receptor for the rhinovirus?
ICAM-1
what is the receptor for the encephalomyocarditis virus?
VCAM-1
Neiserria meningitidis and Staphylococcus aureus both interact with what?
CD14 -> toll-like receptors
what does HIV type 1 use as a initial binding receptor?
CD4
what induces resistance to viral infection in cells?
Type I INF's (INF-alpha, INF-beta)
what is the biggest inducer of interferon in self-cells?
presence of double stranded RNA
what does activation of INF cause to happen in cells?
increased expression og MHC class I and antigen presentation
what happens to cells that produce INF?
the are killed by NK cells
Class 2 INFs (INF-gamma) cause what changes in cell expressions?
increase expression of both MHC I and II
NK cells stimulated by type 1 INFs will produce what?
Type 2 INFs
IFN-alpha is usually produced by?
macrophages
IFN-beta is usually produced by?
fibroblasts
what activates NKT cells?
lipid-containing antigens presented by CD1 molecules
what type of MHC's are CD1?
class 1b MHC molecules
what T cells are involved in innate immunity?
IL-17 producing CD4 T cells
what is the function of IL-17
attract neutrophils to site of infection
what B cells are involved in innate immunity?
B-1 cells
are ligands for B1 cells bound to MHC and if so what MHC molecule?
no
are ligands for gamma/delta T cell bound to MHC and if so what MHC molecule?
yes, MHC class 1B
what are ligands for NK cells bound to?
CD1
what is the general recognition function NK cells do?
recognize alteration or absence of MHC class I molecules on virus-infected target cells
what are KIRs?
Killer-cell Immunoglobulin-like Receptors
what is special about KIR NK cell receptors?
the bind to the same place as T cell receptors on MHC class 1 molecules
what are the class I HLA MHC molecules that KIRs can bind?
HLA-A, HLA-B, and HLA-C
what is the function of KIRs?
to both inhibit and activate NK cells depending on the specific receptor
what are the MHC-like molecules which activate NK cells to kill cells which are stressed?
MIC-A, Mic-B, and RAET1
what is the mechanism that NK cells kill other cells?
induce apoptosis via release of granzymes, perforins, and other factors
how can some viruses trick NK cells into letting live in a cell?
the create MHC I-like which tricks NK cells into thinking they are looking at a normal cell (acts as inhibitor to release of apoptotic factors)
do NK cells recognize peptide presented by MHC class I molecules?
no they only recognize the MHC class I molecule as self or foreign, but do not recognize peptide presented
what ensures that self-cells are not attacked by NK cells?
all self-cells have at least one inhibitor ligand for an inhibitory KIR receptor on a NK cell
what do NKT cells recognize?
lipid antigens presented in association with CD1
upons binding lipid antigen associated with CD1, what do NKT cells do?
they produce IFN-gamma or IL-4 which activates NK cells, macrophages, and dendritic cells
what is the first type of T cell to appear in embryology?
gamma/delta T cell
what is the suggested function of gamma/delta T cells?
protection of against infection in epithelial cells
how do gamma/delta T cells know when epithelial cells have been infected?
they recognize stress molecules on epithelial cells
describe the memory response in gamma/delta cells?
there is none
what receptor on NK cells allows them to bind to MIC-A and MIC-B presented by cell in stress?
NKG2D
B-1 cells all produce what antibody?
IgM
the IgM produced by B-1 cells has a general affinity for what?
carbohydrate antigens
what is the suggested function of B-1 cells?
protect body cavity from infection
what is produced within the first 2 days of infection? (4)
1. IFN-alpha
2. IFN-beta
3. TNF-beta
4. IL-12
what occurs in the innate immune response between day 2 and day 6?
NK cell-mediated killing of infected cells
what happens from day 6 to day 10?
T-cell mediated killeing of infected cells, Igm goes to IgG for neutralization
what signaling molecules do virally infected cells produce to let effector cells around them become aware of their infection?
type I interferons (IFN-alpha and IFN-beta)
what happens to the numbers of T cells released from the lymph nodes (efferent lymph duct numbers) during an infection?
the drop very low becuase they are trapped to be presented antigen
what types of antigen do dendritic cells transfer to the lymph nodes?
both intracellular and extracellular presented on MHC class I and II molecules
what cytokine makes NK cells produce INF-gamma?
IL-12
what makes IL-12 in response to antigen binding?
dendritic cells
CD4 T cells which are differentiation during IFN-gamma and IL-12 production become what kind of helper T cells?
TH1 cell
what cytokines do TH1 cell secrete? (3)
1. IL-2
2. IFN-gamma
3. TNF-beta
what delivers antigens from the gut lumen to lymphoid tissues?
M cells
how does IgA get to the gut lumen?
transcytosis through the gut epithelium
where do all the activated lymphocytes of the MALT originate?
peyers patches becuase this is where they are indtroduced to antigen
how do activated lymphocytes of MALT get to the various mucosa from the peyers patches?
in the blood stream
what carries IgG antibodies across vessel endothelium?
Brambell Receptor (FcRB)
what is the antibody Fc receptor found on mast cells specific for?
IgE Fc region
in addition to opsinization, what other function does compliment have in gram+ bacteria?
causes lysis with C9 pore structure
how to T cells get into secondary lymphoid tissue?
they enter via HEVs
what do dendritic cells specifically express that allows them to attract naive T cells?
chemokine DC-CK
how long does it take to get antigen-specific T cells into circulation?
2-days
the presence of what cytokines facors TH1 production?
IL-12 and IFN-gamma
the presence of what cytokines favors TH2 production?
IL-4 and IL-6
what does the cytokine IL-10 act as?
a immunosuppresent cytokine
what produces IL-10 and TGF-beta (switch factor for IgA)?
CD4+CD25+ T regulatory cells
which naive B cells are trapped in secondary lymphoid tissue?
the ones that are bound by antigen specific TH2 cells
where does hypermutation occure?
the germinal center of the lyphoid follicle
how long does it take for a naive T CD4 T cells to become a TH2 cell after an encounter with antigen?
5 days
what forms the primary focus in secondary lymphoid tissue?
newly differentiated TH2 cells with associated B cells proliferate to form primary focus
how do circulating B cells enter secondary lymphoid tissue?
through HEVs
B cells that go straight to the medulla, proliferate (7-6 times), and differentiate into plasma cells live how long?
2-3 days, function mainly in IgM production
what allows B cells to survive hypermutation in the germinal centers?
binding antigen/antibody complexes the fastest on follicular presenting cells (limited antigen to the highest affinity takes it away from lower affinities)
what happens to the B-cells which have high affinity hypermutations?
they migrate to the medulla to replace the current IgM plasma cells and differentiate into IgG producing plasma cells
viruses cause dendritic cells to release what?
IL-12
what does IL-12 do to NK cells?
causes them to release INF-gamma
what does the presence of INF-gamma and IL-12 do to CD4 T cell differentiation?
biases it towards TH1 cells
what are the cytokines made by TH2 cells that inhibit TH1 cell growth?
TGF-beta and IL-10
what cytokine do TH1 cells secrete which inhibits growth of TH2 cells?
IFN-gamma
cytosolic pathogens can only be taken care of by what immune effector cell?
CD8 T cells
intracellular pathogens withing macrophage vesicles are destroyed by which immmune effector cell?
TH1 T cells
pathogens from the extracellular fluid can be destroyed by which immune effector cells?
CD4 TH1 or TH2 cells
why is the TH1 cell important in TH2 activity?
it produces IL-2 which is needed for TH2 proliferation
what is the organims that breaks out of phagolysosomes and infects macrophages?
lysteria
what effector cell is needed to deal with lysteria?
CD8 cytotoxic cells
what do antibodies do for pathogens within macrophage vesicles?
the function only as opsonizing agents
why are TH1 cells necessary to get pathogens which are inside phagolysosomes in macrophages?
the secrete INF-gamms which helps the macrophage become active against the pathogen
what is the role of antibodies in extracellular pathogens?
they act as neutralizing agents and opsonins
in addition to the activty of antibodies, what else helps tag extracellular pathogens?
the classical pathway compliment system classical pathway
memory B cells can be specific for one of which antibody isotypes?
IgG, IgA, IgE
describe a memory B cell
resting B cell which has already undergone isotype switching and can produce high-affinity clones
what allows memory B cells to be very good APCs?
high level of MHC II expression
what is the result of successive immunizations with the same antigen?
increased antibody affinity for the antigen
what is the distinct difference between memory and naive T cells?
the amount of CD45
what are the two types of CD45 displayed on T cells?
CD45R0 and CD45RA
which CD45 is most prevelant on memory T cells?
CD45RO
do naive T cells or memory T cells have more CAMs?
memory T cells
most second exposure infections are mediated soley by what cells?
Memory B and T cells not naive because their affinity is too low to be effective at the same rate as memory cells
what are the cytokines released by CD8 T cells?(3)
1. IFN-gamma
2. TGF-beta
3. TGF-alpha
what are the macrophage effector molecules? (5)
1. IFN-gamma
2. GM-CSF
3. TNF-alpha
4. CD40L
5. Fas Ligand
what releases the macrophage effector molecules?
TH1 cells
what are the B cell activating effector molecules?(4)
1. IL-4
2. IL-5
3. IL-13
4. CD40L
what produces the B cell activating effector molecules?
TH2 cells
what is the interleukin that is involved in neutrophil recruitment?
IL-17
what do you give to Rh negative mothers to prevent their rejection of a second Rh+ fetus?
RhoGAM
what is the function of RhoGAM?
it prevents naive B cells from differentiating into plasma cells which produce antibody against Rh+ antigen, but CANNOT stop memory B cells from making antibody
what is the term given to the ability of some viruses to switch around peices of themselves to avoid recognition?
antigenic variation
what is the technique employed by the herpes virus to escape immune defenses?
it lies dormant until the memory cells have died down and it can succesfully cause an infection
what bacterium prevents fusion of phagosome with lysosome?
mycobacterium tuberculosis