Immunology Flashcards
What factors stimulate monocyte differentiation into macrophages?
M-CSF
GM-CSF
What factors influence development of dendritic cells from CD34+ stem cells?
GM-CSF
SCF
TNF-a
IL-4
TGF-B1
What is the common progenitor cell of histiocytes?
CD34+ stem cells
What type of adhesion molecule is expressed by all leukocytes?
Beta 2 integrins (CD11/CD18)
What type of beta-2 integrin is expressed by Langerhans cells and interstitial dendritic cells?
CD11c
What beta-2 integrin is expressed by macrophages?
CD11b (and CD11d by macs in spleen/bone marrow)
What is expressed on the cell surface of Langerhans cells?
C-type lectin
Langerin
What tissue does not contain interstitial dendritic cells?
Brain
What markers are expressed by interstitial dendritic cells in the skin?
CD1a
CD11b
CD11c
MHC class II
CD90 (Thy-1)
What are the only cells that can activate naive T-cells?
Dendritic cells
Where are classical dendritic cells found?
Dermis
Name 4 stimulators of type 1 classical dendritic cells
dsRNA (TLR3)
LPS (TLR4)
flagellin (TLR5)
nucleic acids (TLR7/9)
What do type 1 classical dendritic cells express on their surface once activated?
MHC I
What cytokine do type 1 classical dendritic cells secrete once activated?
IL-12
What 2 cytokines suppress IFN-gamma production in the hair follicle and account for immune privilege in the follicle?
alpha-MSH
TGF-B1
What factors stimulate type 2 classical dendritic cells?
IL-10
TGF-a
histamine
PGE2
parasitic worms
LPS
Where are plasmacytoid dendritic cells found?
Bone marrow
Blood
Lymphoid organs
What are the primary stimulators of plasmacytoid dendritic cells?
viral nucleic acids
What cytokine is secreted in large amounts by plasmacytoid dendritic cells?
IFN-a (type I interferons)
What cells contain Birbeck granules?
Langerhans cells
What cytokines encourage Langerhans cells to migrate from the epidermis to the lymphatics?
TNF-a
IL-1Beta
Where are Merkel cells found?
Tylotrich pads
HF bulge
What happens to immature dendritic cells if they do not encounter antigens within a few days?
They die
What stimuli cause immature dendritic cells to mature?
IL-1
TNF-a
PAMPs
DAMPs
What type of MHC are exogenous antigens attached to?
MHC class II
What type of MHC are endogenous antigens attached to?
MHC class I
What type of T-cells are activated by IL-12 secretion from dendritic cells?
Th1
What type of T-cells are activated by IL-1 and IL-6 secretion from dendritic cells?
Th2
What TLRs are involved in dendritic cell activation of Th1 cells?
TLR3
TLR4
TLR5
TLR7
TLR9
What TLRs are involved in dendritic cell activation of Th2 cells?
TLR1
TLR2
TLR6
What cytokine secreted by dendritic cells will activate Th17 cells?
IL-23
What type of T-cell will develop when IL-12 is absent?
Th2
What type of T-cell will develop when IL-12 is present?
Th1
What are the 3 mechanisms of immune tolerance by dendritic cells?
T-cell anergy
Clonal deletion
Induction of Tregs
What are the IHC markers for Langerhans cells in dogs?
CD1c
CD11c
CD80
MHC-II
What is the relationship between # of Langerhans cells and atopy?
Langerhans cells are increased in dogs with atopy
What type of immunity is reliant on complement?
Innate
What IHC markers are expressed by T helper cells?
CD4+ (CD3+, CD8-)
What marker is expressed by cytotoxic T-cells?
CD8+ (CD4-, CD3+)
What factor is essential for mast cell development?
Stem cell factor (c-kit ligand)
Which MHC molecule presents antigens to CD4+ T-cells?
MHC II
Which MHC molecule presents antigens to CD8+ T-cells?
MHC I
What IHC markers are expressed by Tregs?
CD3+
CD4+
CD25+
FoxP3+
What IHC markers are expressed by NK cells?
CD3+
CD16+
CD56+
What is the function of Tregs?
Suppress function of other T-cells
What marker is expressed by memory B-cells?
CD27
What type of T-cell are Th17 cells?
CD4+ (T-helper cell)
What type of T-cell are Th1 cells?
CD4+ (T-helper cell)
What type of T-cell are Th2 cells?
CD4+ (T-helper cell)
What is the site of maturation of B-cells?
Bone marrow and spleen
What is the site of maturation of T-cells?
Thymus
What type of adhesion molecule is responsible for low-affinity adhesion of circulating WBC to endothelial cells?
Selectins
What selectins are expressed by endothelial cells?
E-selectin
P-selectin
Which endothelial cell selectin is stored in granules and rapidly expressed in response to histamine?
P-selectin
What selectin is produced in response to IL-1 and TNF during infection?
E-selectin
What is the major ligand for P-selectin expressed by circulating leukocytes?
Sialyl Lewis X
What type of selectin is expressed on leukocytes?
L-selectin
Which chemokines recruit neutrophils?
CXCL1
CXCL8 (IL-8)
What allows for high-affinity binding of leukocytes to the endothelium during rolling?
Chemokines on endothelial cells binding to receptors on leukocytes
What ligand binds to integrin VLA-4 on on leukocytes?
VCAM-1 (on endothelial cells)
What ligand binds to integrins LFA-1 and Mac-1 on leukocytes?
ICAM-1 (on endothelial cells)
What type of junction must be disrupted in order for leukocytes to leave the blood and enter tissue?
Adherens junctions between endothelial cells
What chemokine receptors are expressed by neutrophils to allow for chemotaxis?
CXCR1
CXCR2
What chemokine receptor is expressed by monocytes to allow for chemotaxis?
CCR2
What chemokine is produced by tissue cells to recruit monocytes to tissue?
CCL2 (binds to CCR2 on monocytes)
What cell wall lipid serves as a PAMP for gram-positive bacteria?
Lipoteichoic acid
What cell wall lipid serves as a PAMP for gram-negative bacteria?
LPS
What are DAMPs?
endogenous molecules released by damaged/dying cells
What is the term for the class of receptors that recognize PAMPs and DAMPs?
PRRs (pattern recognition receptors)
What TLR do motile bacteria bind to?
TLR5
TLR11
(flagellin binding)
What TLR binds to dsRNA?
TLR3
What TLRs binds to ssRNA?
TLR7
TLR8
What TLRs are activated by heat shock proteins and HMGB1?
TLR2
TLR4
Which TLRs are expressed on the plasma membrane and sense extracellular PAMPs?
TLR1
TLR2
TLR4
TLR5
TLR6
TLR11
TLR12
What TLRs are expressed within cells on the ER and endosomal membranes?
TLR3
TLR7
TLR8
TLR9
TLR10
TLR13
What protein in the endoplasmic reticulum is essential for TLRs to localize to endosomes?
UNC-93B (deficient individuals are susceptible to viral infections)
What is one of the primary transcription factors that is activated when a TLR is bound?
NF-kB
Which TLR is NOT involved in the activation of NF-kB?
TLR3 (it activates type I interferons)
What 3 type of PRRs are present in the cytosol rather than on cell membranes?
NOD-like receptors
RIG-like receptors
cytosolic DNA sensors
What TLR recognizes DNA viruses?
TLR9 (+/-TLR3)
What TLRs recognize protozoa?
TLR9
TLR11
TLR12
What TLR regulates TLR2 responses and suppresses inflammation?
TLR11
What TLRs have been associated with Leishmania disease progression in dogs?
TLR2 upregulation
TL4 downregulation
TLR7 downregulation
TLR9 downregulation
What type of lymphocytes predominate in generalized demodicosis?
CD8+
What do RIG-like receptors sense?
Viral RNA
What do C-type lectins recognize?
Microbial carbohydrates
What type of C-type lectin is expressed by Langerhans cells?
Langerin (CD207)
What does TLR4 recognize?
LPS
What does TLR5 recognize?
Bacterial flagellin
What does TLR1 recognize?
Bacterial lipopeptides
What does TLR2 recognize?
Bacterial peptidoglycan
What does TLR3 recognize?
dsRNA
What does TLR6 recognize?
bacterial lipopeptides
What does TLR7 recognize?
ssRNA
What does TLR8 recognize?
ssRNA
What does TLR9 recognize?
CpG DNA
dsDNA
What does TLR11 recognize?
Profilin
Flagellin
What does TLR12 recognize?
Profilin
What does TLR13 recognize?
Unmethylated bacterial RNA
What cells of the skin are the most versatile sensors of PAMPs and DAMPs?
Dendritic cells
What cytokine is produced by ILC1s (innate lymphoid cells)?
IFN-gamma (intracellular microbe defense)
What transcription factor is expressed by ILC1s?
T-bet (similar to Th1 cells)
What cytokines are produced by ILC2s (innate lymphoid cells)?
IL-5
IL-9
IL-13
(helminth defense)
What transcription factor is expressed by ILC2s?
GATA-3 (like Th2 cells)
What cytokines are produced by ILC3s?
IL-22
IL-17
(extracellular bacteria and fungi defense)
What IHC markers would denote an NK cell?
CD3-/CD56+
What is the primary cytokine produced by NK cells?
IFN-gamma
What proteins are contained within NK cell granules and are released when NK cells are activated?
Perforin
Granzymes
Which cytokines activate NK cell-mediated killing?
IL-12
IL-15
An NK cell recognizes MHC class I on a potential target. Is the target cell likely to be killed?
No–the NK cell will be inhibited so that killing does not occur (normal cells should express MHC class I)
Which part of complement is triggered by mannose-binding lectin?
Lectin pathway
What part of complement is triggered by the binding of C1q to the Fc portion of microbial antibodies?
Classical pathway
What part of complement is triggered by the recognition of microbial surface structures by C3?
Alternative pathway
What proteins make up the membrane attack complex?
C5b
C6
C7
C8
C9
What protein serves as an opsonin in the complement cascade?
C3b
What pathway of complement is antibody-mediated?
Classical pathway
What antibody is most efficient at complement-binding?
IgM (>IgG)
What is the function of the membrane attack complex?
Cause cell lysis
What is the function of complement?
Opsonization
Promote phagocytosis
Stimulate inflammation
Name the 3 most important inflammatory cytokines of the innate immune system.
TNF-a
IL-1
IL-6
What are the main cell types that produce TNF-a?
Macrophages
Dendritic cells
IL-12 and IFN-gamma are secreted during antigen presentation to a naive T-cell. What cell is it likely to become?
Th1 cell
IL-1, IL-6, and IL-23 are secreted during antigen presentation to a naive T-cell. What cell is it likely to become?
Th17 cell
IL-4, IL-25, IL-33, and TSLP are secreted during antigen presentation to a naive T-cell. What cell is it likely to become?
Th2 cell
What is the effect of IL-6 on B-cells?
Promotes antibody production
What cytokine inhibits macrophage and dendritic cell activation (i.e. anti-inflammatory)?
IL-10
What is the term for the antigen-binding portion of an antibody?
Fab region
What part of an antibody molecule is involved in effector functions?
Fc region
Which 2 antibodies are involved in complement activation?
IgG
IgM
What is the function of MHC molecules?
Bind and display peptides to be recognized by CD4+ and CD8+ T-cells
What chemokines attract APCs into LN for presentation to T-cells?
CCL19
CCL21
(bind to CCR7 receptor on dendritic cells)
What type of MHC molecule is expressed on almost all nucleated cells?
MHC class I
What is the main cytokine that stimulates expression of MHC class II?
IFN-gamma
What are the 4 major subsets of CD4+ T-cells?
Th1
Th2
Th17
Treg
What is the defining cytokine of Th1 cells?
IFN-gamma
What is the major function of Th1 cells?
Macrophage activation
What are the defining cytokines of Th2 cells?
IL-4
IL-5
IL-13
What are the main effector functions of Th2 cells?
Mast cell and eosinophil activation
What are the defining cytokines of Th17 cells?
IL-17
IL-22
What are the major functions of Th17 cells?
Neutrophil recruitment and activation
What chemokine receptors are expressed in high levels by Th1 cells (but not Th2)?
CXCR3
CCR5
What chemokine receptors are expressed in high levels by Th2 cells?
CCR3
CCR4
CCR8
Which chemokine receptor is expressed in high levels by Th17 cells and what is its ligand?
CCR6
Binds to CCL20
What type of organism drives Th1 cell development?
Intracellular microbes
What type of organism drives Th2 cell development?
Helminths
What type of organism drives Th17 cell development?
Fungi
Some bacteria
Which ligand is present on Th1 cells and serves to activate macrophages to kill intracellular bacteria?
CD40L
What antibody is likely to be produced by a B-cell when stimulated by IL-4?
IgE
What cytokine is the primary activator of eosinophils?
IL-5
What cytokines are important for CD8+ cell differentiation?
IL-2
IL-12
IL-15
IL-21
type I interferons
What are the major cytotoxic proteins in granules of CD8+ T-cells?
Granzymes
Perforin
(same as NK cells)
What are the 2 mechanisms of cytotoxic T-cell-mediated killing?
Perforin and granzymes
Fas and FasL
What is the primary cytokine produced by CD8+ T-cells?
IFN-gamma
What complement pathways are activated by extracellular bacteria?
Alternative
Lectin (if the bacteria express mannose on their surface)
What type of bacterial infection requires cell-mediated immunity: intracellular or extracellular?
Intracellular
What is generated by COX-2?
Prostaglandins
What combination of cytokines is responsible for sickness associated with inflammation (fever, lethargy, malaise)?
TNF-a and IL-1
What cytokine is a “master regulator” that triggers and maintains allergic inflammation at barrier surfaces?
TSLP
What type of cell does IL-25 attract?
Eos
What cytokine family is IL-31 a member of?
IL-6
Which histamine receptor plays a major role in IL-31 release?
H2
What is CXCL8 also known as?
IL-8
What 2 chemokines are major neutrophil attractants?
CXCL8
CXCL2
