Immunology Flashcards
IL1
Causes fever, acute inflammation.
HOT T-bone stEAK meaning
1 - IL1 causes fever "hot" 2 - IL2 stimulates T-cell 3 - IL3 stimulates bone marrow 4 - IL4 stimulates IgE production 5 - IL5 stimulates IgA production 6 - IL-6 stimulates acute phase protein production
IL8
“Clean up on Isle 8”
IL8 recruits neutrophils to clear infection
once it has recruited the macrophages it induces phagocytosis and promotes angiogenesis
IL12
induces differentiation into Th1 subtype
TNFa
what is it produced by (3)
what are threeactions (3)
produced by mast cells, macrophages and Th1 cells mediates septic shock
WBC recruitment via increased expression of selectins and integrins
vascular leakage
formation and maintenece of granulomas
INFg (3 roles) one main role
produced by NK cells and Th1 cells to activate macrophages to kill phagocytosed microbes
- main macrophage activating factor
- activate the phagocyte oxidase system in macs
- makes macrophages become epitheliod cells in granulomas
IL10
attenuates the inflammatory response. decreases MHCII and TH1 cytoines. works along with TGFb
receptors of the innate immunity are encoded in the
germline
TLRs are expressed on
cells of the innate immune system (DC, macrophages, neutrophils, mast cells)
TLR-4 is expressed where and binds what
on the plasma membrane and binds tp LPS
TLR-3is expressed where and binds what
on the endosome and binds dsDNA of virus
TLR 4 can activate what two pathways
1: TLR4 recruits MyD88 –> NFkB –> production proinflammatory cytokines
2: TLR4 recruits TRIF –> interferon regulatory factors (IRF) –> INFa and INF b
Describe the inflammasome pathway
The inflammasome pathway oligomerization of several proteins (NLRP3) in response to microbial products –> caspase 1 activation. Cas1 will cleave pro IL1 to make IL1. ) (remember IL1 –> Feeever)
cell classically responsible for linking the innate and adaptive immune reponses
DCs
plasmacytoid DCs produce
Type 1 INF
what stimulates expansion of NKs
IL15, IL12, IFNa and b
in inhibitory receptor of an NK call binds to?
MHCI - in an infectedc ell, MHC I will be drecreased and so will not be able to engage with the inhibitoyry NK receptor –> killing by NK cells
the body protects against Helminths mainly by
mast cells, basophils and eosinophils
the second signal for the activation of immune cells is provided by
innate immunity molecules such as IL6, C3b, IL12 and by B7 costimulatory molecules int he case of T cells
most commong Ab found in the blood
IgG
which antibodies have 4 repeating Ig domains
IgM and IgE
Which antibodies ahve 3 repearing Ig domains
IgA, IgD and IgG
IgE exists as a
monomer
IgA exists as a
multimer
IgM exists as a
multimer
IgG exists as a monomer
monomer
Ab involved in opsonization
IgG
primary antibody that crosses the placental barrier?
IgG
IgM exists as a
monomer and exists on the surface of B-cell
allotype refers to
polymorphisms in the constant regions of heavy and light chains that differ btw individuals
idiotype
distinguished from one another by their hypervariable regions
epitope
site on antigen that Ab recognizes
valency
number of antigenic determinants posessed by an antigen
affinity v avidity
affinity means Kd, Avidity means number of binding sites
Active v Passive immunity
in active immunity, a microbial antigen is given to a person and they develop immunity to that antigen due to formation of memmory cells. Passive immunity is when you give the serum (with antibodies) from the serum of an immune indivisual, but you do not develop memory.
name of the enzyme that ass random nucelotides to a TCR
TdT : terminal deoxy-transferase
name of the enzyme that rearranges the DNA segments of a TCR
RAG
what is the first signal in the TCR activation series?
the first signal is the binding of a TCR-CD4/8 complex with MHC
what is the second signal in the TCR activation series/
the second signal is the binding of CD28 in the T-cell by B7 on the DC
TH1 cells secrete
INFg
Th1 cells action?
activate macrophages to kill phagocytosed microbes
help B-cells by promoting class switching to complement binding antibodies IgG1 and IgG3
Th2 cells activate
B-cells
Th2 cells secrete
IL4 and IL5
Th17 cells do what?
activate neutrophils
Th17 cells produce
IL17 and IL22
Tregs produce
IL10 and TGFb
what do tregs do?
they help to regulate the immune system and suppress immune rsponses
what kind of t-cell protects against intracellular organisms
Th1 cell
what cytokine drives the induction of a Th1 cell?
IL12 and INFg
what induces TH2 cells?
IL4
Th2 cells produce what?
IL4, IL5
effect of Th2 cells?
IgE antibody induction
direct effect of IL5?
activates esoinophils
drect effect of IL4
IgE antibody production
IL4 and IL13 will illicit
an alternatively activated macrophage
define a classical macrophage, or M1
a macrophage that is activated by INFg. they act in the “classical”way and are involved in killing and phagocytosis
describe alternatively activated macriphages
they are activated by IL4 and IL13 and produce TNFb and IL10. they ahve antiinflammatroy effects and are involved in wound healing
what illicits a TH17 cell?
TGFb, IL6 and IL23
what is the effect of IL17
recruits neutrophils , involved in defending against extracellular bacteria and fungi
IL22 effects?
Promotes inflammation
receptor necessary for B-cell and T-cell joining?
CD40
CD40 and CD40L are expressed on what
CD40 is expressed on the B-cell
CD40L is expressed on the T-cell
what is required for germinal center rxns to start?
CD40-CD40L
hyper IgM syndrome is caused by
mutations in CD40 or CD40 L; these are required for the germinal center rxn of a b-cell where it will undergo class switching. no class switching = only IgM
what is the function of short lived plasma cells
they branch off of the Thelp pathway and secrete yuge amounts of IgM antibody for a short amount of time before dying
long lived plasma cells do what?
they return back to the bone marrow where they secrete a yuge amount of IgG specific to the Antigen
memory B-cell v long lived plasma cell?
re-exposure leads to re-activation and rapid proliferation and antibody secretion. only memory cells these show memory upon re-eposure
How is a CD4+ memory T-cell activated again?
ou only need one signal which can be the TCR and MHC peptide expressed on B-cells.
what types of cells are part of the myeloid lineage?
monocytes, macriphages - aka phagocytes. they are involved in innate immunity
polymorphonuclear cells are
eosinophils, basophils, and neutrophils
cells of the lymphoid lineage
t lymphocytes
b lymphocytes
NK cells
where in the spleen do lymphoctes counter antigen presented by an APC and is activated
in the white pulp
where do T and B lymphoctes enter the lymph node
through the HEV
3 actions of Thelper cells
- produce cytokines to activate macrophages that have phagocytosed antigens
- actiavte neutrophils through cytokines
- help b cells to produce antibodies and T-cells to proliferate
what are TLRs presented on?
TLRs are presented on innate immunity cells: macrophges, DC, neutrophils.
what are the two downstream effects of TLR stimulation?
engaging MyD88 –> activationNFkB and proinflamatory cytokines
engaging TRIF –> activation of IRF3 and production of IFN a&b
what is an inflammasome
it is a multiprotein complex tht activates inflammatory processes
how does the inflammasome work?
assembly of multiple complexes leads to cas1 activation and results in cleavage of pro-IL1 and secretion of IL1
cells that link adaptive and innate response
DC
Dcs produce what in response to infection
INF a
what is the inhibitory signal for NKs
MHCI
difference in B and T cells binding to antigen?
B-cells an bind directly to antigens whereas Tcells can only respond to antigen presented by MHC on an APC
function of IgA
mucosal immunity
function of IgE
immedaite hypersneistiviy and helminths
IgG function (4)
- opsonization,
- complement activation,
- antibody dependent cell-mediated cytotoxicity,
- neonatal immunity
IgM f(x)
naive B-cell antigen receptor. compliment activation
allotype defintion
polymorphisms in the Fc of heavy and light chains that differ btw individuals
idiotype refers to
antibody molecules that can be distinguished by their hypervariable regions
when are antigen - antibody complexes the smallest?
when antigens or antibodies are in excess
first step in recruitment of leukocytes
cells adhere to upregulated selectins
second step in recruitment of leukocytes to a site of inflammation
integrins on the surface of leukocytes get activated by chemokines and itneract with ICAM1 expressed on the surface of the endothelium
what do neutriphils express that help them to get into a site of infxn?
ligands for P and E selectin express LFA1 (binds to ICAM)
what do monocytes express that helps them to get into the site of infxn?
ligands for P and E selectin
VLA-4 that binds to VCAM1
what are acute phase proteins
these are proteins expressed by the liver that coat the microbe surface & f(x) as opsoin
include CRP, serum amyloid proteins and mannose binding lectin
in chronic granulomatous disease
there is a deficiency in NADPH
what are the two systems of killing microbes in macrophages
1 - phagocyte oxidase system
2- proteolytic enzyme productioin
what is the phagocyte oxidase system in marophages
inducible iNos, induced by INFg, geneated ROS, NO and toxic radicals. Can use arginine
what are the proteolytic enzymes in a macrophage?
activated by an increase in pH –> generation of cathespin G
How do neutrophils kill?
- bacterium is phagocytosed by a neutrophil
- The phagosome fuses with granules
- the pH of the phagosome rises and microbe is killed
- pH of phagosome decreases and phagosome and lysosome merge. bacterium degrqaded
- neutrophilic apoptosis
- remnants phagocytosed by a macrophage
acute inflammation will consist of
edema and infiltration by neutrophils
transudate
disturbance of hydrostatic or osmotic pressure. no increase in vascular permeability
exudate
due to inflammation - due to an increase in vascular pereability
main mediators of vasodillation
histamine, NO, PGI2 and PGE2
what is seratonin released by
platelets
the three major pro-inflammatory cytkines are
IL1 IL6 and TNFa
the major antiinflammatory cytokines are
IL10 and TGFb
4 major plasma derived systems that play a key role in inflammation
kinin system
coagulation system
fibrinolytic system
complement system
Factor XII and Hageman factor
when there is damage to the endothelium it gets activated by interacting with negative components wand will activate all of the plasma derived systems. kinin, coagulation, fibrinolytic, complement
what is the kinin system
produces vasoactive kinins, such as bradykinins –> vasodilation, permeability and pain
the clotting system action
induces formation of thrombin –> inflammatory properties
the fibrinolytic system
produces plasmin and degrades fibrin –> inflammation
the complement system
produces C3a and C5a, anaphylotoxins
a burn will cause what type of inflammation
serious
where would you characteristically find fibrinous inflammation?
lining of the body cavities, meninges and pericardium
are the vascular leaks large or small in fibrinous inflammation
they are very large
acute appendicitis is a good example of
a purulent inflammation
what is an abscess
localized collection of purulent inflammatory tissue caused by suppuration in a tissue, and organ or a confined space
2 bacteria that are associted with pseudomembraneous infections
c.diff and diptheria
ulcers are asssociated with what type of necrosis
liquefactive
acute inflammation ends due to what 3 signaling molc.
lipoxins from Arachadonic Acid
resolvins
IL10 & TGFb
langerhans giant cells
in granulomatous inflamamtion activated macrophages fuse to form - nuclei are arrenged around the periphery of the cell in a horshoe pattern
foreign body giant cells
in granulomatous inflammation macrophages fuse - nuceli are haphazardly arranged
granulomas have ____ necrosis in the middle
caseus
shift to the left refers to
when TNF causes release of neutrophils from the BM, including immature forms
see neutrophilia in response to
an acute inflammation
see lymphocytosis in response to
viral infections
see monocytosis in response to
chronic inflammation
see eosinophilia in response to
allergic rxns
rouleaux formations may indicate
acute inflammation: inflammation –>increase in fibrinogen –> decrease in negative charge on RBCs –> increased erythrocyte sedimentation rate
T-cells itneract with macrophages in order to
boost the macrophage response. aka the t-cell is telling the macrophage what to do
TCR cannot bind peptides unless they are bound by an______
MHC
which TCR chain rearranges first?
the TCR b chain because it is more complicated
name of enzyme that rearranges the thymocye to create the CDR
RAG
name of the enzyme that adds random nucelotides to a TCR
TdT
define positive selection
makes sure that a thymocyte can bind to MHC I or II and will make it a CD4 or CD8 positive cell
define negative selection
if a t-cell binds to a “self” antigen presented in the thymus it is marked for killing
what is signal two needed to initiate t-cell activation?
the binding of CD28 on the T cell and B7 on the DC
Tregs produce what
TNFb and IL10
Th1 stiulates what kind of antibody switching?
IgG1 and IgG3
Th2 stimulates what class switching?
IgE
Th1 protect against
intracellular microbes and recruit neutrophils
Th17 cells protect against
extracellular bacteria and fungi
Th2 cells protect against
helminths
which antibodies mediate the complemnt system
IgG and IgM
which antibody is responsible for neutralization of microbes and toxins?
IgG
which antibody is responsible for activation of the classical pathway of complement?
IgG and IgM
which antibody is responsible for mucosal immunity?
IgA
which antibody is responsible for OPSONIZATION of antigens for phagocytosis by macrophages and neutrophils?
IgG
which antibody is responsible for eosinophil and mase-cell mediated defense?
IgE
which antibody is responsible for antibody dependent cellular cytotoxicity
IgG
which antibody is responsible for
neonatal immunity: transfer of maternal antibody across plawcenta and gut
which antibody is responsible for feedback inhibition of B-cell activation?
IgG
What is Fc Rn, what is it used for and how does it work?
Neonatal Fc receptor
It will bind IgG in the endosome and then release IgG - allows recycling of the IgG –> its really long half life
which Ab circulates in the blood?
IgG
which Ab is in the mucosa?
IgA
the binding of the Fc receptor of an antibody that is coating a microbe will bind to a phagocytic cell and cause
phagocytosis, killing of Ig coated cell and degranulation of mast cells and eosinophils
which receptor on an NK cell binds to IgG coated cells leading to phagocytosis of the microbe and killing?
FcgRIII
what receptor on an NK cell will bind to helminth coated with IgE leading to eosinophil deganulation?
FceR1
name of the receptor that transports IgA
poly-ig receptor
what antibodies are transported across the placenta to the baby
IgG
what antibodies do neonates get from breast milk?
IgG
products of the complement system covalently bind
microbial cell surface, ab bound to microbes and ab bound to tissue
what part of the complement system is important for nisseria infections?
Membrane attack complex
for encapsulated bacteria, which complement system will be most effective?
classical due to the MAC
deficiency of what leads to lupus
C2/C4 –> inability to make C3b for clearance via CR1 binding
C1 inhibitor will
is a serine protease inhibitor that will cause th dissociation of C1s ad C1r from C1q
DAF
is an inbitor of complement whihc binds to C3b or C4b, which are components of C3 concertase in classical and alternative, respectively, and keeps them from cleaving C3
S protein
will bind to C7 and C8 of the complement system and prevent them from inserting themsleves into the membrane forming the MAC
CD59
inhibits C9 polymerization –> MAC failure
intracellular microbes induce what kind of T-cells
Th1
extracellular microbes induce what kind of T-cells?
Th2
in fungal infections what kind of immune response is detrimental to the host?
Th2
IFNg induces
macropages
viral replication is inhibited by
INFa and INfb
what kind of T-cell response do you want in parasitic infections?
Th1
what is the prinipal mediator of septic shock?
TNFa
mechanism of antigenic variation for the influenza virus?
antigenic shift
what is antigenic shift
reassortment of virus RNA genomes responsible for influenca virus
what is the purpose of using an adjuvant
adjuvants will illicit innate immune rsponses and ehance T and B cell responses.
the best vaccines produce
a high affinity neutralizing antibody & memory cell
what are the chemotactic factors that neutrophils follow when trafficking to a site of infection
C5a, LTB4, bacterial products and IL8
the MPO system occurs in what cell type
neutrophils and monocytes - NOT macriphages
il8
chemotaxis
IL6
increased liver synthesis of acute ohase proteins
what is granulation tissue
it is the vascularized tissue composed of blood vessels and activated fibroblsts
what recruits cells for granuloma formation
tnf a and INFg
What occurs in healing by primary intention?
fibrin clot –> neutrophilic infilatration –> macrophages –> granulation tissue –> collagen type III –> remodeling to type I collagen
healing by second intention is when
wound contraction is caused due to increased numbers of fibroblasts
cytokine responsible for acute phase protein release from the liver
IL6
INFg induces class swithcing to
IgG
IL4 induces class switching to
IgE
termiantion of acute inflammation by
Lipoxins
resolvins and
TGFb
HSP ROLE
They participate in the process of protecting newly formed polypeptides from misfolding (chaperones) and help the cell get rid of already misfolded or damaged proteins by binding them to ubiquitin and thus making them targeted for digestion by specific proteases (cellular housekeeping)
another name for necoptosis
programmed necrosis
does necroptosis use caspases?
NO
nexroptosis uses what enzymes
RIP1 and RIP3
in what kind of cells does pyroptosis occur in?
occurs in cells infected by microbes
oyroptosis ivoles the actiation of
Cas 1 which cleaves pro-IL1 to make IL 1
SIRTUINS
Sirtuins are thought to promote the expression of several genes whose products increase longevity. Include proteins that inhibit metabolic activity, reduce apoptosis, stimulate protein folding, and inhibit the harmful effects of oxygen free radicals.
Organs with dual blood circulations like intestines and lung undergo what type of necrosis
hemorrhagic
cd16 / FcgRIII is
the receptor that an IgG that is opsonizing a microbe will use to signal to a phagocytic cell
t dependent antigens are usually
polysacharrides
how does e. coli undergo antigenic variation?
pilli mutations
antigenic shift responsible for influenza pandemic
reassortment of virus RNA genome
most effective vaccines are
those that produce high affinity neutralizing Abs nad memory cells
how do adjuvants works
they illicit innate immune responses via IL12 and enhance T cell and B cell responses
when are Th2 responses deady to the host?
Fungi and protazoa
chemotactic agents
LTB4, C5a, IL8
vasodilation is mediated by
prostaglandins
