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149 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What 2 cell types can pluripotent hematopoetic stem cells diffentiate into?
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1) Common lymphoid progenitor.
2) Myeloid stem cell. |
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What 5 types of cells can common lymphoid progenitors differentiate into?
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1) B lymphocyte
2) NK cell 3) NK-T cell 4) T lymphocyte 5) Flt3+ DC precursor |
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What 7 types of cells can myeloid stem cells differentiate into?
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1) Flt 3+ DC precursor
2) CFU-GM (granulocyte-macrophage) 3) CFU-Eo (eosinophil) 4) CFU-Baso (basophil) 5) CFU-MC (mast cell) 6) CFU-Meg (megakaryocyte) 7) CFU-E (erythrocyte) |
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What 2 stem cell types may give rise to Flt 3+ DC precusors?
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1) Common lymphoid progenitor
2) Myeloid stem cell |
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What 2 cell types may arise from a Flt3+ DC?
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1) Plasmacytoid dendritic cell
2) Dendritic cell |
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What 2 stem cell types may give rise to (non-plasmacytoid) dendritic cell?
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1) Monocyte
2) Flt 3+ DC precusor |
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What are 2 cytokines that are produced by neutrophils in substantial amounts?
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1) TNF
2) IL-12 |
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What are 2 characteristic cytokines that are produced by monocytes/macrophages?
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1) IL-12
2) IFN-gamma |
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What are 2 subtypes of macrophages?
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1) Classically activated macrophages
2) Alternatively activated macrophages |
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What are 2 functions of classically activated macrophages?
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1) Proinflammatory cytokine production. What 4 cytokines, in particular?
2) Antibacterial activities |
1) IFN-gamma
2) IL-6 3) IL-12 4) TNF |
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What 3 cytokines induce formation of "alternately activated macrophages"?
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1) IL-4
2) IL-10 3) IL-13 What is the function of alternatively activated macrophages and what 3 cytokines do they produce? |
Function to release antiinflammatory cytokines:
1) IL-10 2) IL-1 receptor antagonist 3) TGF-beta |
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What is the hallmark cytokine responsible for eosinophil production and survival?
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IL-5
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True or false: all MHC bearing cells can be induced to express APC function?
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True, if stimulated appropriately.
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What is the function of plasmacytoid dendritic cells?
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Function in antiviral host defense.
What is the hallmark cytokine that plasmacytoid dendritic cells produce? |
Type I interferons
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What chromosome contains the MHC gene complex?
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Chromosome 6 (short arm)
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What chromosome contains the beta-2 microglobulin chain?
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Chromosome 15
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What domain of the MHC class I molecule interacts with CD8?
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alpha-3 domain
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What domains of the MHC class I molecule contain an Ig-domain?
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alpha-3 domain, beta-2 microglobulin
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What domains of the MHC class I molecule contain the antigen binding groove?
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alpha 1 and alpha 2
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What MHC class is associated with "endogenous" antigens?
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Class I
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What is the proteasome?
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A cytoplasmic protein that digests cytosolic proteins into peptide fragments that can be transported for presentation by MHC class I molecules.
What cytokine induces production of the immunoproteasome? |
IFN-gamma
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4 steps from cytosolic protein to antigen presentation in MHC class I?
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1) Degradation by proteasome/immunoproteasome.
2) Transport into ER by TAP 3) In ER, loading onto protein-binding groove under direction of Tapasin, Calreticulin and oxidoReductase Erp57 (TCR!!!) 4) beta-2 microglobulin induces dissociation of calnexin and stabilizes complex for transport through golgi to exocytic vessicles to cell surface. |
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What is "cross presentation"?
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When proteins are endocytosed and displayed to T-cells via MHC class I molecules.
In what infectious process is cross presentation especially important? |
Viral infections.
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What domains create the antigen binding groove in the MHC class II molecule?
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alpha-1 and beta-1
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What domain interacts with CD4 on MHC class II molecules?
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beta-2
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What chaperone protein assists the invariant chain (Ii) into a binding position in the antigen binding groove?
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Calnexin
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What class of MHC molecule utilizes the invariant chain (Ii) for stabilization prior to antigen binding?
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Class II
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What molecule catalyzes the exchange of an invariant chain (Ii) for an antigen?
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HLA-DM
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What HLA type is associated with anklyosing spondylitis?
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HLA-B27
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What HLA type is associated with a much higher risk of IDDM?
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HLA-DQ2/DQ8
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What HLA type is associated with protection from IDDM?
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HLA-DQ6
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What HLA type is associated with nonresponsiveness to Hep B vaccination?
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HLA-DR3 (you have to go to the DR 3 times for Hep B vaccination)
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What 2 HLA haplotypes are associated with seronegativity after measles vaccination?
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HLA-DRB1*03
HLA-DRB1*0201 |
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What MHC class does CD1 resemble?
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MHC class I
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What 2 types of molecules are presented by CD1?
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glycolipids
glycosphingolipids |
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What are MICA and MICB?
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stress-inducible MHC class I-related chains A and B?
What is their function? Where are their genes located? |
Function to serve as targets for gamma-delta T-cells.
Genes located in between the MHC class III complex and the MHC class I genes on chromosome 6. |
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Do NK-T cells express CD4 or CD8?
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Neither. (They are double negative.)
What do NK-T cells recognize? |
Glycolipid antigens presented by CD1d molecule.
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What is the function of NK-T cells?
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Immunoregulatory.
What are 4 key cytokines that NK-T cells release? |
IFN-gamma, IL-4, GM-CSF, TNF
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What enzymes initiate the rearrangement of V(D)J regions in lymphocytes?
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RAG1 and RAG2
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What 6 enzymes repair cleaved V(D)J segments?
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DNA-dependent protein kinase (DNA-PK), Ku, XRCC4, XLF, DNA ligase IV, Artemis. (Art KU D D X X)
Are these enzymes lymphocyte specific? |
No!
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What is the role of TdT?
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TdT (terminal deoxynucleotidyl transferase) adds nucleotides to some of the VDJ junctions, providing extra junctional diversity
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In what section of the thymus do prothrombocytes differentiate, proliferate and rearrange their TCR beta chains?
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The subcapsular space
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In what section of the thymus does alpha chain rearrangement occur, potentially forming a functional mature TCR?
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cortex
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In what section of the thymus does positive selection occur?
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cortex
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In what section of the thymus does negative selection occur?
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medulla
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What protein is expressed in the thymic medulla that is responsible for negative selection?
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autoimmune regulator (AIRE)
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What syndrome is caused by defective expression of AIRE?
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autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
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What protein is not expressed in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy?
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AIRE
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What percentage of developing T cells survive postive and negative selection in the thymus?
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<5%
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Where are gamma-delta T cells generated?
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Not the thymus (extrathymic compartment)
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What components make up the CD3 complex?
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CD3 gamma
CD3 delta CD3 epsilon CD3 zeta |
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CD28 interacts with what stimulatory ligands?
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CD80 or CD86
Which one is on the T-cell? APC? |
CD28 on T-cell
CD80/86 on APC |
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What is the role of CD45?
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Deactivating T-cell activation pathways/
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In the blood, are T-cells mostly CD4 or CD8?
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CD4
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What characteristic nuclear protein is expressed in natural T-reg cells?
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Foxp3
What characteristic CD markers are expressed in natural T-reg cells? |
CD25, CD4
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What 2 characteristic cytokines are expressed in natural T-reg cells?
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IL-10, TGF-beta
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What characteristic natural T-reg cytokine can act in membrane-bound form, requiring cell-cell contact?
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TGF-beta
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What are the two types of T-reg cells?
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1) Natural T-reg cells
2) Adaptive (induced) T-reg cells |
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What cytokine drives the production of adaptive T-reg cells?
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IL-10
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What 2 cytokines are characteristically produced by adaptive T-reg cells?
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IL-10!!!!!
TGF-beta |
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What epigenetic features are required for stable Foxp3 expression?
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DNA methylation and histone acetylation around the Foxp3 promoter.
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What characteristic nuclear protein is expressed in adaptive T-reg cells?
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Foxp3 (variable expression)
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What percentage of T-cells in the blood are CD4-CD8- (double negative)?
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5-10%
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What cytokine is characteristically produced by Th0 cells?
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IL-2
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What is the characteristic cytokine that drives Th1 development?
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IL-12
What 2 cell types characteristically produce IL-12? |
Macrophages and NK cells.
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What is the characteristic cytokine that drives T-cell differentiation toward a Th1 phenotype?
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IL-12
What 2 cell types characteristically produce IL-12? |
Macrophages
NK cells |
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What is the characteristic cytokine that drives T-cell differentiation toward a Th2 phenotype?
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IL-4
What 3 cells types characteristically produce IL-4? |
NKT cells
Basophils Mast cells |
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What are the 2 characteristic cytokines that drive T-cell differentiation toward a Th17 phenotype?
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TGF-beta
IL-6 What cell types characteristically produce these cytokines to drive Th17 differentiation? |
Unknown
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Expression of what nuclear transcription factor is characteristic for Th1 T cells?
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Tbet (T-box transcription factor)
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Expression of what nuclear transcription factor is characteristic for Th2 T cells?
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GATA3
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Expression of what nuclear transcription factor is characteristic for Th17 cells?
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RORC2 (retinoic-acid-related orphan receptor c isoform 2)
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What are the 3 cytokines characteristically produced by Th1 cells?
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IL-2
IFN-gamma lymphotoxin |
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What are the 5 cytokines characteristically produced by Th2 cells?
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IL-4
IL-5 IL-9 IL-13 GM-CSF |
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What are the 2 cytokines characteristically produced by Th17 cells?
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IL-6
IL-17 |
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In general, what type of Th cell supports cell-mediated immunity?
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Th1
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In general, what type of Th cell supports humoral immunity?
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Th2
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In general, what type of Th cell supports neutrophil response to extracellular bacteria
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Th17 (supports neutrophil response)
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What adjuvant has recently been shown to demonstrate the feasability of reprogramming the Th2 response to a Th1 response?
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CpG DNA
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How does a superantigen work?
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By binding, without proteolytic processing, to both a MHC molecule outside the antigen-binding groove and to TCR proteins outside of their antigen-MHC binding site.
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Is the amino terminus of an antibody the constant or varible region?
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variable
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Is the carboxy terminus of an antibody the constant or variable region?
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constant
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On what chromosome is the kappa light chain encoded?
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chromosome 2
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On what chromosome is the lambda light chain encoded?
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chromosome 22
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On what chromosome is the heavy chain locus?
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chromosome 14
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How many different exons encode the various constant regions of the immunoglobulin protein?
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9 (IgD, IgM, 2 IgA, 4 IgG, IgE)
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What cytokine is produced by bone marrow stromal cells to drive differentiation of stem cells to the b cell lineage?
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IL-7
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What immunoglobulin chain is rearranged first: lamda, kappa or heavy?
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Heavy.
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During b cell development, when is TdT expressed?
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During the time of D-to-J and V-to-DJ rearrangement.
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What 2 proteins act as surrogate light chains?
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lambda5
VpreB |
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What are the 2 molecules that are associated with membrane-bound immunoglobulin to facilitate intracellular messaging?
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Ig-alpha
Ig-beta |
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What are the 3 proteins that compose the B-cell coreceptor complex?
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CD19
CD81 CD21 (complement receptor 2) |
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Quick B-cell activation pathway (9 steps)?
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1) Src family kinases (blk, fyn, lyn) phosphorylate ITAM's on Ig-alpha and Ig-beta
2) Syk tyrosine kinase activated 3) BLNK activated 4) Phospholipase C activated 5) Guanine nucleotide exchange factors 6) Activation of protein kinase C 7) Calcium mobilization 8) Ras/Rac-dependent activation of mitogen-associated protein kinases 9) Activation of new gene transcription |
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How are IgM and IgD expressed at the same time?
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Alternate RNA splicing of VDJ exon to mu or delta exons.
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What 4 enzymes mediate immunoglobulin isotype class switching?
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1) RNA editing enzyme activation-induced cytidine deaminase.
2) uracil DNA glycoslyase 3) APE1 (endonuclease) 4) DNA-PK (DNA repair enzyme) |
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What cytokine is characteristic for driving class switching to IgG1 and IgG3?
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IL-10
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What 2 cytokines are characteristic for driving class switching to IgE?
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IL-4
IL-13 |
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What cytokine is characteristic of driving class switching to IgA?
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TGF-beta
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What 4+ enzymes are required for somatic hypermutation?
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1) activation-induced cytidine deaminase.
2) uracil DNA glycosylase 3) APE1 4) DNA repair enzymes |
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Is CD40 expressed on B-cells or T-cells?
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B-cells
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Is CD40L expressed by B-cells or T-cells?
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T-cells
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What happens to CD80/CD86 expression when B-cells take in antigen?
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Increased expression of CD80/CD86.
How does a T-cell respond when presented with presented with both antigen and CD80/86 |
T-cell increases CD40L expression (which consequently drives class switching in B cells)
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On what chromosome does CD40L reside?
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X chromosome
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What characteristic genetic defect results in x-linked hyper IgM syndrome?
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CD40L deficiency
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What characteristic genetic defect results in autosomal recessive hyper IgM syndrome?
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CD40 mutations
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Does somatic hypermutation occur in most T-cell independent antibody responses?
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No.
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What chemical is especially important in regulating the egress of cells out of lymphoid tissues and into the circulation?
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lycophospholipid sphingosine-1-phosphate
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What system is used by most cytokines to initiate gene transcription?
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Jak-STAT
Specific janus kinase (Jak) associates with the cytoplasmic domain of the cytokine receptor; Jak phosphorylates its respective STAT protein, causing the STAT protein to dimerize and translocate to the nucleus |
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What does Jak3 deficiency cause?
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SCID
How? |
Absent signalling of gamma-c protein, a subunit of several cytokine receptors
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What 6 cytokines use gamma-c protein as part of their receptor?
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IL-2
IL-4 IL-7 IL-9 IL-15 IL-21 |
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Where is gamma-c protein encoded?
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X-chromosme.
Why is this important? |
x-linked SCID
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What is STAT1 deficiency associated with?
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Susceptibility to mycobacteria and variable increase in susceptibility to viral infections.
Why? |
Impaired ability to respond to Type I or Type II interferons.
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What is heterozygous STAT3 mutation associated with in humans?
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Autosomal dominant hyper IgE syndrome.
Why? |
Deficiency of Th17 differentiation.
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What is STAT4 deficiency associated with?
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Impaired Th1 development due to defective IL-12 signal transduction.
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What TLR is activated by CpG DNA?
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TLR9
Why is this important? |
It is the molecular basis for diverting Th2 to a Th1 responses.
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MyD88 deficiency is assocaited with what type of infection?
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Life-threatening, recurrent pyogenic infection.
How? |
Defective signalling through TLR common pathway.
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Are nucleotide-binding domain leucine-rich repeat proteins cytosolic or membrane bound?
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Cytosolic.
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What type of receptor recognizes intracellular signals of cellular damage, such as uric acid crystals?
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NLR's (nucleotide-binding domain leucine-rich repeat proteins)
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Upon activation, what 2 molecualr pathways can NLR's activate?
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1) Apoptosis
2) NF-kappa beta transcription to induce a broad proinflammatory respons |
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What 3 cytokines are characteristically produced by the inflammasome?
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1) IL-1
2) IL-18 3) IL-33 |
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How does alum work, on a molecular level, to promote antibody response?
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Alum is taken up by phagocytic cells. NALP3 activated. Inflammasome activated.
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What 3 proteins compose the inflammasome?
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1) NALP3 (a NLR)
2) Capase 1 3) Apoptosis-associated-speck-like protein containing a capase recruitment domain (ASC) What happens if one of these proteins is absent or defective? |
No response to alum as an adjuvant for the antibody response.
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What is dectin-1?
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Transmembrane receptor that contributes to the innate immune response.
What does it bind? |
beta-glucans on the cell walls of yeast
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What are the 3 major collectins in human subjects?
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Mannose binding lectin
Surfactant protein A Surfactant protein D What do they recognize? |
Microbial carbohydrates.
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What are the 3 major types of pentraxins?
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Short pentraxins
C-reactive protein Serum amyloid P-component |
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What 4 types of molecules does C-reactive protein bind?
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bacterial low density lipoproteins
bacterial polysaccharides apoptotic host cells nuclear material What does it induce? |
Complement
Phagocytosis |
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What 3 types of molecules does serum amyloid p-component bind?
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microbial carbohydrates
nuclear substances amyloid fibrils |
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What types of molecules do ficolins bind?
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Carbohydrates
What happens after binding? |
Complement activation through the lectin pathway.
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What are chitinases?
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enzymes that digest chitin, a major constituent of the cell walls of fungi, helminths, insects and crustaceans.
Why are they important? |
Chitin is a potent inducer of Th2 response, levels of chitinase are dramatically increased in the lungs of asthmatic subjects and may be a target for drug development in asthma.
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Where do NK cells develop?
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The bone marrow.
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What 2 cytokines characteristically play a role in the differentiation of NK cells?
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IL-2
IL-15 |
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How is the cytotoxic activity of NK cells inhibited?
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Inhibitory receptors that recognize MHC class I molecules (in absence of MHC class I, cells are targeted)
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What 2 pathologic mechanisms are inhibited by NK cells?
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Viral infection
Tumor |
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What is the activating signal for the classical complement pathway?
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Antigen-antibody complexes.
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Classical complement pathway (in order).
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C1, C4, C2, C3, C5, C6, C7, C8, C9
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What is the activating signal for the alternate complement pathway?
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microbial structures that neutralize inhibitors of spontaneous complement activation.
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What is the activating signal for the lectin complement pathway?
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mannan-containing microbes with plasma MBL
What 2 proteins are associated with activation of the lectin pathway? |
MBL associated serine protease 1 and 2.
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Deficiency of c4 or c2 leads to what clinical disease?
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lupus-like immune complex diease.
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Deficiency of decay-accelerating factor leads to what clinical disease?
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paroxysmal nocturnal hemoglobinuria
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What cell types express selectins?
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leucocytes
endothelial cells What cell types express selectin ligands? Are selectin-selectin ligands high affinity or low affinity? |
Leucocytes
Low affinity |
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What cell types express integrins?
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leucocytes
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What is the ligand for lymphocyte function-associated antigen 1 (CD11a/CD18, alpha-L/beta-2) integrin?
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intercellular adhesion molecule 1 (adhesion molecule)
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What is the ligand for very late antigen 4 (CD49d/CD29, alpha-4/beta-1) integrin?
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vascular cell adhesion molecule (adhesion molecule).
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What is the ligand for Mac-1 (CD11b/CD18, alpha-M/beta-2) integrin?
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intercellular adhesion molecule 1/C3b (adhesion molecule)?
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What are LFA-1, VDLA-4 and Mac-1?
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Integrins
Where are integrins expressed? What are the ligands for integrins? |
Integrins are expressed on leucocytes.
Ligands for integrins are expressed on vascular endothelium and are called immunoglobulin domain cell adhesion molecules |
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What cellular homestastic function do TNF family molecules induce?
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Apoptosis.
Through what type of receptor does TNF family pathway induce apoptosis? |
Type I TNF receptor
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What ligand characteristically transmits apoptotic signals during thymic T-cell selection?
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Fas
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What clinical problems arise from a defect in Fas or FasL?
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Autoimmune disorders with prominent lymphoproliferation.
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What cell type is converted to fibroblasts in tissue changes that lead to fibrosis?
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epitheleal cells
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Levels of thymic stromal lymphopoeitin are increased or decreased during pregnancy?
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Increased
Leading to production of what cytokine by placental dendritic cells? |
IL-10
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