Block 1 Flashcards
what are cytokines
molecules involved in cell signaling that bind to specific cell surface receptors, mediating a downstream effect
what are 4 examples of cytokines
interleukins
interferons
colony stimulating factors
tumor necrosis factor
what cells are included in the myeloid lineage
granulocytes
monocytes
what cells are included in the lymphoid lineage
agranulocytes
NK cells
what cells are granulocytes
neutrophils
eosinophils
basophils
what are CD markers
antibody tags to tag specific types of cells
what is flow cytometry used for
to phenotype individual cells
in flow cytometry, what does forward scatter look at
how big the cell is
in flow cytometry, what does side scatter look at
degree of granulation
MHC is represented as an __
ID badge
what type of innate immune cells also act as antigen presenting cells
macrophages
dendritic cells
what are naive lymphocytes
lymphocytes before they encounter and respond to an antigen
MHC class I pathway is restricted to __ T cells (CD__ cells)
killer
CD8
MHC class II pathway is restricted to __ T cells (CD__ cells)
helper
CD4
what 2 cell types are phagocytes
neutrophils
macrophages (monocytes in blood)
do phagocytes (neutrophils and macrophages) function as part of the innate or adaptive immune system
innate
phagocytes (neutrophils and macrophages) are important in what bodily response
inflammation
what cell is the first line of defense against microorganisms
neutrophils
are neutrophils more mobile or stationary
mobile
what is the main mechanism of bacterial destruction
oxidative burst (toxic oxygen derived products)
what is oxidative burst
rapid release of superoxide and H2O2
what are the 3 enzymes involved in oxidative burst
NADH oxidase
superoxidase dismutase
myeloperoxidase
what does NADPH oxidase do in oxidative burst
NADPH–>NADP+H+
what does superoxide dismutase do in oxidative burst
superoxide–>H2O2
what does myeloperoxidase do in oxidative burst
H2O2–>HOCl (hypochlorate ions+hydroxyl radicals)
what are neutrophil extracellular traps (NETS)
if a bacteria/virus is too big to handle, neutrophils release nucleus contents
can be used to attach bacteria which are included in a biofilm due to increase size to destroy
how does classical activation of macrophages (M1 macrophages) work
ingestion of apoptotic cells
secretion of cytokines to amplify protective response against microbes
act as antigen presenting cells
how does alternative activation of macrophages (M2 macrophages) work
help to repair damaged tissues
which phagocytes, neutrophils or macrophages, active the nitric oxide system
macrophages
which phagocytes, neutrophils or macrophages, release cytokines
macrophages
on an NBT reduction test, a purple or pink color means oxidative burst is working
purple
are mast cells part of innate or adaptive immunity
innate
what is the function of mast cells
release inflammatory mediators
what 2 main inflammatory mediators are released by mast cells
histamine
tryptase
what receptors do mast cells have
IgE
what is the function of eosinophils
release of major basic proteins by binding to antibody tagged parasites
when are mast cells increased
parasitic infection
allergic response
allergy
aromatic poisoning
what is the main function of dendritic cells
antigen presenting cells
what are the main cells that lead the transition from innate to adaptive immune response
dendritic cells
what type of cells can B cells differentiate into
plasma
what is the purpose of B cells differentiating into plasma cells
plasma cells secrete antibodies (immunoglobulins)
B cells can either be __ or __
naive
memory
T cells can either be __, __, or __
naive, effector, memory
what is the function of B lymphocytes
antibody production
for antibody production, B cells often need help from what other cells
T cells
T lymphocytes can either be killer, helper, or __
regulator
what is the function of innate lymphoid cells
start immune response
secrete cytokines
where are innate lymphoid cells found
within tissues (especially mucosal tissues)
what is the function of NK cells
recognize and kill infected cells
what are the 3 main functions of innate immunuty
inflammation
anti-viral response
eliminate damaged tissue/initiate tissue repair
what are the 3 main physical defenses to microbes
epithelial barrier
cilia
mucous
what is the complement system
an interaction between plasma and surface proteins in defense against pathogens
what are the 3 main functions of complement
opsonization
recruitment of phagocytes (especially neutrophils)
kill microbes
how does an “a” subunit differ from a “b” subunit in complement
“a” floates Away
“b” stays Bound
what is opsonization
coating the surface of a molecule so they can be more easily picked up by phagocytes
what complement proteins form the membrane attack complex
C5b
C6
C7
C8
C9
what is the purpose of the membrane attack complex
create a hole in the bacterial cell membrane
what complement proteins are the main mediators of inflammation (anaphylatoxins)
C3a
C5a
what is the main complement protein of opsonization
C3b
what is the main complement protein for phagocytosis/clearance
C3b
what is the main complement protein for B-lymphocyte activation
C3d
what antibody binding activates the classical complement pathway
which one does more
IgG and IgM
IgM
how does C1 inhibitor (C1 INH) regulate the classical and lectin pathway activation
prevents accumulation of C1r2s2 to prevent complement from becoming overactive
what condition is the result of lack of C1 inhibitor for regulation of complement
hereditary angioedema
overactive complement
what complement pathway runs continuously and spontaneously at low levels in blood plasma
alternative
what 2 regulatory proteins of complement prevent complement from attacking out cells
Factor I
Factor H
what 3 regulatory proteins on mammalian cells prevent complement from attacking our cells
membrane cofactor protein (MCP/CD46)
complement receptor 1 (CR1)- promotes C3b and C4b decay
decay accelerating factor (DAF)
how does Factor I work in complement
it, along with MCP and CR1, degrade C3b and C4b
how does Factor H work in complement
it removes Bb from C3 convertase in alternative pathway
how does decay accelerating factor work in complement
it accelerates the decay of C3 and C5 convertase
what does deficiency in decay accelerating factor (DAF) lead to
paroxysmal nocturnal hemoglobinuria
what is required for membrane attack complexes
an accessible plasma membrane on the target cell
what microbes are resistant to membrane attack complexes
encapsulated bacteria
gram + and acid fast bacteria
nonenveloped viruses
what 2 things inhibits membrane attack complex
CD59 (prevents formation)
S protein (prevents insertion in plasma membrane)
if mammalian cells don’t have CD59 for membrane attack complex inhibition, what is the result
paroxysmal nocturnal hemoglobinuria
how does CR1 (complex receptor 1) work
stimulates phagocytosis
what part of complement is CR1 specific for
C3b
C4b
how does CR2 (CD21) work
it’s part of B cell coreceptor and a receptor for Epstein Barr virus
what 2 systems are used for recognition of problem in innate immune response
PAMPs
DAMPs
what do NOD-like receptors bind to
viral RNA
what do RIG -like receptors bind to
bacterial peptidoglycan
what do cytosolic DNA sensors detect
DNA in cytosol
*DNA should not be in cytosol
what does TLR1:TLR2 recognize
bacterial lipopeptides
what does TLR2 recognize
bacterial peptidoglycan
what does TLR4 recognize
LPS (lipid A) of gram - bacteria
what does TLR5 recognize
bacterial flagellin
what does TLR2:TLR6 recognize
bacterial lipopeptides
what TLRs (Toll-like receptors) are found in an endosome
TLR3, 7, 8, and 9
what does TLR3 recognize
dsRNA
what does TLR7 and TLR8 recognize
ssRNA
what does TLR9 recognize
CpG DNA
what transcription factor is associated with release of proinflammatory cytokines, stimulating adaptive immune response
NF-kB
what transcription factor is associated with release of type 1 interferons, leading to an anti-viral response
IRF7 and IRF3
deficiency in UNC93B leads to susceptibility to ___
viral infections
what are interferons a class of
cytokines
what are the 2 main function of interferons
induce production of antiviral proteins
induce production of double stranded activated inhibitor of translation which induces the antiviral state in neighboring cells
the antiviral response leads to secretion of what type interferons
1
what are the 2 type 1 interferons released during an antiviral response
IFN alpha and beta
once there is increased MHC class 1 expression and antigen presenting in all cells, what cells are activated (in the correct order)
dendritic cells and macrophages then NK cells
cytosolic DNA sensors for PAMPs and DAMPs recognize what and activate what
recognize dsRNA
IFR pathway
what are the 3 types of cytosolic receptors for PAMPs and DAMPs
cytosolic DNA sensors
NOD-like receptors
RIG-like receptors
what do RIG-like receptors recognize
dsRNA and DNA-RNA combinations
what makes up an inflammasome
sensor protein+adaptor protein+caspase1
caspase 1 cleaves __ in an inflammasome
IL-1beta inflammatory cytokine to become active
what are 4 main categories of signaling in the immune system
non-receptor tyrosine kinase based receptor
tyrosine kinase receptor
nuclear hormone
G-protein coupled receptor
which of the 4 main categories of signaling in the immune system causes a change in shape
G-protein coupled receptor
JAK/STAT, which is used as a __ receptor, is a signal transducing activator of ___
cytokine
transcription
how is cytokine signaling mediated by JAK/STAT
every receptor uses a different JAK/STAT complex
the activation of endothelial cells causes cells to move from __ to __ for an immune response
blood to tissues
what causes leukocytes to roll and bind weakly on endothelium to activate endothelial cells for an immune response
selectin binding
what causes leukocytes to stick on endothelium to activate endothelial cells for an immune response
integrins
what type of receptors are chemokines
G-protein coupled receptor
signaling through chemokine receptors induce expression of what
integrins
what are 3 forms of protective immunity against infections located in interstitial spaces, blood, or lymph
complement
phagocytosis
antibodies
what are 2 forms of protective immunity against infections located on endothelial surfaces
antimicrobial peptides (especially in mucous)
antibodies (especially IgA)
what are 2 forms of protective immunity against cytoplasmic intracellular infections
NK cells
cytotoxic T cells
*antiviral response
what is a form of protective immunity against vesicular intracellular infections
T cell and NK cell dependent macrophage activation
innate immunity occurs between __ and __ hours
0-4
adaptive immune response occurs after __ hours
96
what do defensins do
disrupt microbial cell membranes
what do cathelicidins bind
LPS
what are the 5 signs/symptoms of inflammation
redness
heat
swelling
pain
loss of function
what is the immediate reaction of inflammation (before the inflammation process of vasodilation begins)
vasoconstriction
what are the phases of inflammation
- stimulus
- vasoconstriction, mast cell activation
- vasodilation (redness), endothelial cell contraction (leaky blood vessels), transudate release
- diapedesis of erythrocytes (increased sedimentation rate of RBC), rouleaux (stacking) of RBC
- emigration of lymphocytes (especially M2 macrophages)
- resolution (fibrin deposition)
- healing
what 4 things are released by mast cells during an inflammatory response
histamine (increased vascular permeability, vasodilation, pain)
platelet activating factor (recruitment of neutrophils)
prostaglandins (edema)
leukotrienes (chemotaxis to bring in leukocytes)
what enzyme is involved in mast cells chewing their own membrane lipoproteins, causing membrane blebbing and release of components during an inflammatory response, activating the arachidonic acid pathway
phospholipase
what are 2 functions of circulating platelets during inflammation
produce CXCL8 to help move neutrophils from blood to tissues
produce oxygen radicals
what starts the classical pathway of complement
C1 binds to antibody-antigen complex on surface of pathogen
what does C1 cleave in classical pathway of complement
C4 into C4a and C4b
C2 into C2a and C2b
what forms C3 convertase in classical and lectin binding complement
C4b2b
what does C3 convertase cleave in complement
C3
what are the 2 main complement components of inflammation
C3a
C5a
what is the main complement component of opsonization
C3b
what starts the lectin binding pathway of complement
mannose binding lectin protein complexes with mannose on surface of pathogen
what does MBLP cleave in lectin binding pathway of complement
C4
C2
what is C5 convertase in classical and lectin binding complement pathway
C4b2b3b
what forms C3 convertase in alternative complement pathway
C3bBb
what forms C5 convertase in alternative complement pathway
C3 convertase+C3b
what cleaves Factor B into Ba and Bb in alternative complement pathway
Factor D
what causes the initiation of late steps of complement
C5 convertase cleaves C5 into C5a and C5b
what starts the alternative pathway of complement
C3 is cleaved through hydrolysis into C3a and C3b
what are the 4 steps involved in neutrophils beginning rolling to migration
rolling
tight binding
diapedesis
migration
what is involved in the rolling stage of neutrophil movement during an inflammatory response
selectins expressed on endothelial cells weakly bind to carbohydrates on neutrophils
what is involved in the tight binding stage of neutrophil movement during an inflammatory response
LFA-1 integrin on neutrophil and ICAM-1 on endothelial cell create a stronger interaction due to LFA-1 confirmational change induced by IL-1 which is secreted by inflamed tissues
what 2 things allows diapedesis of neutrophils to occur during an inflammatory response
CD31
CXCL8 gradient produced by platelets
if there is low LFA, what happens to blood neutrophil count? why
increases
LFA is needed for neutrophils to go from blood to tissues
what type of inheritance is leukocyte adhesion deficiency
autosomal recessive
what causes leukocyte adhesion deficiency
leukocyte interaction with vascular endothelium is disrupted
what are the effects of leukocyte adhesion deficiency
recurrent bacterial infection
increased blood WBC count
no pus during wound healing (neutrophils don’t get to tissue)
delayed umbilical cord separation
what are 3 proinflammatory cytokines
IL-1beta, IL-6, TNFalpha
what cytokines secreted by macrophages produce fever
IL-6, TNFalpha, IL-1beta
what cytokine secreted by macrophages leads to mobilization of metabolites which act on bone marrow
TNFalpha
what cytokine secreted by macrophages leads to local tissue destruction
IL-1beta
what effect does cytokine release from macrophages have on the liver
release of acute phase proteins
what are the 5 acute phase proteins secreted by the liver following cytokine release from macrophages
C-reactive protein
serum amyloid A
fibrinogen
mannose binding protein
complement components
CD__= hematopoietic stem cell
34
what 3 factors are involved in CD34+ to myeloid lineage
IL-3
stem cell factor
thymopoietin
what factor is involved with myeloid lineage to neutrophils
G-CSF (granulocyte colony stimulating factor)
what factor is involved with myeloid lineage to monocytes
M-CSF (monocyte colony stimulating factor)
what factor is involved in CD34+ to lymphoid lineage
IL-7
what 2 factors are involved in lymphoid lineage to T cells
IL-2
IL-7
what 2 factors are involved in lymphoid lineage to NK cells
IL-7
IL-15
what factor is involved in lymphoid lineage to B cells
IL-4
what are the 2 antiviral cytokines released
IFNalpha
IFNbeta
what are the 3 anti-inflammatory cytokines
IL-1beta
IL-6
TNFalpha
what are the 2 regulatory/M2 cytokines
IL-10
TGFbeta
what is an additional cytokine released by M1 macrophages
IL-12
what cytokine does Th1 release
IFNgamma
JAK/STAT mediates what molecule signaling
cytokines
what occurs with interferon gamma receptor deficiency
macrophages are present but not killing because they can’t interact with T cells
what interferon maintains granulomas
IFNgamma
what is the difference between T cells and B cells in regards to antibody recognition
T cells recognize MHC
B cells can recognize antibody floating around
what are the characteristics of high immunogenicity
foreign proteins of large size
immunogen proteins that are too small may require ___ to increase size
a carrier
foreign proteins and glycoproteins induce T dependent or independent humoral immunity with class switching
dependent
polysaccharides induce T dependent or independent humoral immunity with class switching
independent
what antibodies are involved in class switching
IgM—>IgA, IgG, IgE
what is the purpose of adjuvants in an immune response
they tell the immunes system to pay attention
increases inflammation
what is an epitope on an antigen
the region on the antigen that binds the antibody
what are the 2 different possible forms of epitope shape
linear or conformational
what is a disadvantage of a confirmational epitope
if it is denatured, the antigen antibody binding ability wont be maintained
what is the receptor for B cells vs T cells
B= membrane bound Ig
T= T cell receptor
do T cells or B cells bind soluble antigens (free floating antigens)
B
antigens of B cells are either protein, polysaccharides, lipids, or nucleic acids, while antigens for T cells are only ___
proteins
B cell epitopes are either linear or confirmational epitopes, which are T cell epitopes
linear
is binding of an antibody to antigen covalent or noncovalent
noncovalent
what is the difference between the Fab and Fc region of an antibody
Fab- antigen binding region
Fc- bottom part of antibody
Ig light chains can either be __ or __ chains
kappa
lamba
what are the 5 classes of antibody heavy chains
IgA
IgE
IgM
IgG
IgD
what domain of the antibody, variable or constant, bind the antigen
variable
are hypervariable regions found in antibody light chain or heavy chains
both
how many hypervariable regions are found in hypervariable heavy and light chains
3 on heavy, 3 on light
what is the function of Ig hinge regions
allow flexibility
Ig hinge regions are high in what 2 amino acids
cysteine
proline
why is complement pathway only activated by IgM and IgG
they have a C1q binding site needed for the initiation of complement
what portion of antibodies allows for interaction of immune complexes with other cells and innate with adaptive immunity
Fc
what are the 4 ways of immunoglobulin expression
circulating
transmembrane
secreted
cell bound (signal through receptor)
coding and using a different heavy chain is termed what
class switching
what are Ig allotypes
variants of Ig constant region due to amino acid differences
what CD is associated with stem cells
34
what CD is associated with NK cells
56
what CD is associated with T cells
3
what CD is associated with helper T cells
4
what CD is associated with killer T cells
8
what CD is associated with B cells
19/20
what does CD59 cause
the breakup of MAC
what does CD46 cause
break up of C3 convertase
what 2 things does CD21 do
bind to C3d
act as a receptor for Epstein Barr virus
what are antibody idiotypes
unique shape of an antibody variable region
what 2 antibody classes have a J chain
IgM
IgA
what antibody is most common in serum
IgG
what antibody can cross the placenta
IgG
what does IgG provide protection against
blood borne pathogens
what allow for the long half life of IgG
IgG recycling
what is IgG recycling
FcRn (neonate) binds to IgG in an acidic endosome
endosome is recycled and IgG is released back into blood
what differs in the 4 subclasses of IgG
number and arrangement of disulfide bonds
which IgG subclass is best at activating complement
IgG3
which IgG subclass is the most common
IgG1
which IgG subclasses are best at opsonization
IgG1
IgG3
when is IgG4 increased
allergy and anti-inflammatory reactions
which antibody can perform agglutination and precipitation
IgG
what is antibody dependent cell-mediated cytotoxicity
antibody binding to cell leads to opsonization for killing rather than phagocytosis
performed mostly by IgG
what is hemolytic disease of the newborn
mother makes antibodies against baby’s RBC= opsonization of baby Rh+ RBC for phagocytosis by it’s liver cells
what is IvIg
purified, polyclonal Ig pooled from plasma of many donors, used in those with autoimmunity
what is the difference between what the affinity constant and dissociation constant of an antibody tells us
affinity constant- how fast antibody can bind
dissociation constant- how long antibody can bind for
a low or high dissociation constant makes for a better antibody
low
what does it mean to say IgA has a high avidity for antigen
it can still stay bound even though there may be lower affinity due to increase in binding sites
what antibody is reactive to ABO blood groups
IgM
what antibody is the most efficient for complement activation
IgM
what is the first antibody to respond
IgM
where is the main location of IgA
mucosal surfaces
what antibody is the most effective viral aglutinator
IgA
what antibody can be transferred through breast milk
IgA
what allows for IgA and IgM protection against digestive enzymes
secretory component due to J chain
what antibody is not found in serum
IgD
what is the main function of IgD
initial antibody triggering of B cells while bound to the membrane on B cell surface (B cell development)
what 2 antibodies are found on the surface of mature B cells
IgD
IgM
what antibody response to allergic reactions and parasitic infections
IgE
what is multiple myeloma
malignant plasma tumor producing monoclonal antibodies
what is the function of phage display
a gene encoding a protein of interest is inserted into a phage coat protein gene, causing the phage to display the protein on the outside. And containing the gene for the protein inside, resulting in a connection between genotype and phenotype.
These displaying phages can be screened for other proteins, peptides or DNA sequences, in order to detect interaction between the displayed protein and those other molecules
what are the 2 types of antibody light chains
kappa (60%)
lambda (40%)
