Module 2 Flashcards
what stimulates the differentiation from monoblast to monocyte
M-CSF
unactivated leukocytes are found whee
in circualtion
activation of leukocytes leads to
migration to inflamed tissue
when endothelial cells are activated what happens
there is an increase in adhesiveness for circulating leukocytes
adhesion is mediated by what
selectins and integrins
what are selectins
carbohydrate binding plasma membrane adhesion molecules
what do selectins do
mediate the initial steps of low affinity adhesion of leukocytes to endothelial cells
what types of selectins do endothelial cells express
p-selectin and e-selectin
E and P selectin bind to what
leukocyte ligands PSGL-1
expressed exclusively by cytokine activated endothelial cells and is important for the migration of leukocytes
E-selctin
found in secretory granules of endothelail cells when expressed on the cell surface it mediates the binding of leukocytes, lymphocytes or monocytes
p selectin
CD62L
l selectin expressed on the surface of lymphocytes and is the homing receptor for lymph nodes
CD62L function
homing receptor for lymphocytes
P and E selectin are activates by what cytokines
TNF and IL-1
L selectin is expressed by what cells
neutrophils monocytes t cells and b cells
integrins are composed of what polypeptide chains
alpha and beta
what mediates the adhesion of cells to other cells or the extracellular matrix
integrins
what cells express ICAM-1
activated endothelial cells
what is the ligand for ICAM-1
LFA-1
integrins do what in response to intracellular signals
increase their avidity for ligands through activation
what changes avidity
integrin clustering on leukocyte membrane and confirmational changes that enhance the affinity of ligand binding
what is the receptor for chemokine CCL19
CCR7
what is the function of CCL19-CCR7 binding
t cell and dendritic cell migration into t cell lymph node zones
CXCR5 binds to
CXCL13 BCA-1
CXCR function
b cell migration into follicles
CXCL 12 binds to
CXCR 4
function of cxcr 4
regulates stem cell trafficking, inflammation, and tissue regeneration
CXCR4 mutation causes what
neutropenia WHIM
what is WHIM
mutation causing increase in chemokine signaling and a reduction in peripheral leukocytes
selectin selectin ligand interactions are
low affinity
selectin selectin ligand binding causes what
leukocytes to bind detach and bind again causing a rolling of the leukocyte on the endothelium
what stimulates chemotaxis
TNF and IL-1
TNF and IL-1 do what to endothelial cells
increase expression of VCAM-1 and ICAM-1
what is the first and secound leukocytes to enter sites of infection
neutrophils first and then monocytes follow hours later
Leukocyte adhesion deficiency LAD
a defect in LFA-1 that results in bacterial infections, neutrophils cannot be recruited to sites of infection
lymphocyte recirculation
naive t cells move from the blood to lymph nodes and through lymphatics back to the blood
the process by which different lymphocytes enter the lymph nodes or specific tissues is called
homing
naive t cells enter lymph nodes through what
high endothelial venules HEV
rolling of naive t cells on hev is mediated by
l selectin on the t cell binding its ligand GLYCAM-1 on the HEVS
Firm adhesion of t cells to hevs is mediated by
LFA-1 and VLA-4
what increases the binding affinity of integrins
CCL19
the exit of naive t cells from lymph nodes involves what
sphingosine 1 phosphate S1P
SIP to SIP receptors on t cells does what
stimulates movement of the t cells out of the lymph nodes along a SIP gradient
the SIPR level of t cell in the blood is
low
skin t cells express what
CLA-1, CCR4 and CCR10
CLA-1 binds to
E selectin
gut t cells express
LPAM-1 CCR9 and CCL25
LPAM-1 binds to
MADCAM-1
immature b cells leave the bone marrow and
enter the red pulp of the spleen
in the spleen what happens to b cells
they mature into follicular b cells or marginal zone b cells
follicular b cells migrate via
integrins and CXCL13 to the white pulp
follicular b cells migrate where in the spleen
white pulp
what is the egress of b cells from secoundary lymphatic organs dependent on
SIP
microbial substances that stimulate innate immunity are
pathogen associated molecular patterns PAMPs
Molecules produced by damaged or dying cells
damaged associated molecular patterns DMAPS
cell death caused by apoptosis does not release DAMPS
T or F
true
receptors on innate immune cells that bind pamps are
pattern recognition receptor PRR
PAMPS to
PRR
PPRs are encoded where
germline
what type of cells express PRRs
neutrophils macrophages dendritic cells and endothelial cells
membrane spanning proteins that share a common extracellular structural element LRRS flanked by cysteine rich motifs
TLRs
NLRs
nod like receptors
NOD1 and NOD2 are expressed where
cytoplasm
What do NOD 1&2 do
recognize peptides or components of intracellular bacteria
inflammasome
NLPRs respond to cytoplasmic pamps and damps by forming a signaling complex called the inflammasome to generate active forms of IL-1
RLRs
promote the cynthesis of antiviral type 1 interferons
CDS detect to
cytosolic DNA and activate signaling pathways that trigger anti viral responses like the production of type 1 interferons
STING pathway
major mechanism for the DNA induced activation of type 1 interferons
where is sting found
in the endoplasmic reticulum
what activates sting
microbial dna in the cytosol
upon the detection of microbial dna STING
translocates to the golgi and activats IRF3 that induces the expression of type 1 interferons
DAI binds
DNA and acrivates IRF3
AIM2
recognizes microbial DNA and forms the capase 1 inflammasome to process IL-1 and IL-18
scavenger receptors
mediate uptake of oxidized lipoproteins into cells
what are the major scavenger receptors on phagocytes
CD36, CD68, SRB1
defensins
directly toxic to microbes and activates cells involved in inflammation
cathelicidins
LL-37 has directed toxicity against microbes and can activate leukocytes
natural antibodies recognize
lipid or carbohydrate antigen and IgM antibodies
classical pathway
C1 binds antibodies attached to the surface of a microes
major effector mechanism of humoral immunity
classical pathway
alternative pathway
triggered when c3 recognizes PAMPs on microbes and is activated, spontaneous cleavage of C3 normally occurs at low levels and is inhibited by healthy cells
lectin pathway
uses mannose bindign lectin MBL to recognize terminal mannose residues on microbial surface structures
MBL functions similar to
C1
C3 convertase cleaves
C3 into C3a
C3a does what
stimulates inflammation and helps recruit neutrophils to sites of infection and c3b that binds to other complement proteins on the surface of microbes to form the c5 convertase
C5 convertase cleaves
c5 to c5a which is a chemoattractant and c5b which initiates the formation of the membrane attack complex
pentraxins
plasma proteins that recognize pamps or microbial structures
can activate complement and are increased in response to inflammation
CRP SAP PTX3
acute phase reactants
can activate complement and are increased in response to inflammation
Cells of the myeloid lineage
neutrophils, mononuclear phagocytes and dendritic cells.
Cells of the lymphocyte lineage
NK cells, γδT cells (intraepithelial), and B-1 B cells.
soluble mediators
complement, acute phase reactants, and antibodies
what molecules are found in the phagolysosome
ROS,NO, and lysosomal enzymes
what is the first step of phagocytosis
recognition and binding of the microbe
what PRRs are present on phagocytes
C-type lectins, mannose receptors, TLRs and scavenger receptors
phagocytes have receptors called
Fc receptors
Fc receptors
used for opsonin like antibodies that coat microbes or have complement receptors that bind complement on the surface of microbes
once a microbe binds to a receptor on the phagocyte the membrane zips up to form an intracellular vesicle called
phagosome
TLRs function
works together with cytokine receptors to activate phagocytes
once activated phagosomes fuse with
lysosomes to form phagolysosomes
ROS
reactive oxygen species
ROS function
reactive oxidizing agent that kills micrboes and is called respiratory burst
dendritic cells and macrophages that are activated produce what cytokines
TNF, IL-1, IL-6 which are essential mediators of the innate immune system
stimulates IFN-gamma production by NK cells and helps the differentiation of effector cells of the adative immune response
IL-12
enhances the effector function of NK cells
IL-18
enhances nk cell signaling and growth and survival of t cells
IL-15
