Ch 2 Cells involved in Immune Responses

Question 1

what are the pro B cell surface markers?

Answer 1

CD 43, CD19, CD20

Question 2

what are the pre B cell surface markers?

Answer 2

CD 43, CD19, CD20, pre-BCR, cytoplasmic u chain

Question 3

what are the surface markers for immature naive B cells?

Answer 3

CD19, CD20, IgM

Question 4

what are the surface markers for a mature naive B cell?

Answer 4

CD19, CD20, IgM, IgD

Question 5

what stage of B cell development does RAG and TdT perform their actions?

Answer 5

Pro

Question 6

what stage of B cell development hosts heavy chain rearrangement? Light chain?

Answer 6

Pro; pre (k or lambda)

Question 7

what chemokine is expressed on naive mature B cells and what attracts that to the lymph node?

Answer 7

CXCL5 on B cells; CXCL13 gradient created by follicular DC in lymph node follicles

Question 8

where does class switching and somatic hypermutation take place?

Answer 8

germinal centers of lymph node follicles

Question 9

what survival factor maintains plasma cells?

Answer 9

BAFF

Question 10

what survival factor maintains memory B cells?

Answer 10

BCL2

Question 11

what process determines if an Ig is membrane bound or secreted?

Answer 11

alternative splicing of primary mRNA transcript; transmembrane and cytoplasmic exons remain in for membrane-bound; spliced out for secreted

Question 12

what are the survival signals for B cells in the periphery and their receptors?

Answer 12

BAFF, BLYSS, APRIL. Receptors: BR3, TACI (early on), BCMA (later)

Question 13

what are B1 cells?

Answer 13

innate; T cell independent; produce natural antibodies of low affinity that respond to microbes and lipids; found in peritoneal cavity and fetus

Question 14

what are marginal zone B cells?

Answer 14

T cell independent; first responders to polysaccharide antigens (develop by 2 years of age…why infants have poor polysaccharide responses)

Question 15

what are B2 cells?

Answer 15

conventional or follicular B cells, including memory B cells and plasma cells; adaptive; T cell dependent; protein antigens

Question 16

what is the name of the molecule that commits T cells to develop?

Answer 16

Notch

Question 17

what chemokine is expressed by naive T cells and what is the chemokine gradient in nodes?

Answer 17

CCR7 directed by CCL19/21 in perifollicular T cell zone (produced by stromal cells in T cell zone); DC in T cell zone express CCL19 and CCL18 (binds to CCR3 on naive T cells)

Question 18

what are markers of central memory T cells?

Answer 18

CD45RA-, CD27+, CCR7+, CD62L+; effector memory T cells lack all aforementioned markers and home to the peripheral sites

Question 19

expression of what draws T cells out of lymph node and back into circulation?

Answer 19

SIP1 via sphingosine-1-phosphate concentration gradient; SIP1 is internalized if T cell binds cognate MHC

Question 20

describe intrinsic pathway of lymphocyte apoptosis

Answer 20

intracellular stress-> Bim -> Bax/BAK-> cytochrome C-> caspase 9 -> caspase 3; Bcl-2 and Bcl-XL inhibits Bax/BAK

Question 21

desribe extrinsic pathway of lymphocyte apoptosis

Answer 21

lethal ligands and/or repeated lymphocyte activation leads to binding FasL (CD178) to Fas (CD95) -> caspase 8 -> caspase 3

Question 22

which cell is CD14++; CD16-

Answer 22

monocytes; CD14 is part of TLR4 and LPS receptor

Question 23

what are chemokines that attract monocytes to lungs?

Answer 23

CCL2, 3, 4 & 5

Question 24

what do macrophages typically express on their surface

Answer 24

CD14, CD16, CD11b/18 (Mac-1), CD33 and CD 36

Question 25

CD 14

Answer 25

highly expressed on monocytes and macrophages; part of TLR4; binds LPS and activates innate immune responses

Question 26

what cytokine promotes granuloma formation and what cell secretes it?

Answer 26

TNFa; secreted by macrophages

Question 27

what disease process leads to uncontrolled activation of macrophages?

Answer 27

hemophagocytic lymphohistiocytosis (HLH)

Question 28

what are criteria for HLH?

Answer 28

fever, splenomegaly, elevated ferritin (>500), cytopenia of >2 cell lines, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis on smear/bone marow, hepatitis, low NK cells, soluble CD25 (IL2 R) >2400

Question 29

what virus leads to fatal HLH? and in what immunodeficiency? What is the mutation?

Answer 29

EBV leads to fatal HLH in boys with XLP; mutation is SH2D1A-> encodes SAP protein

Question 30

what are distinguishing markers for plasmacytoid DCs?

Answer 30

CD 123 (lack CD11c); conventional have CD11c, CD1, CD13, CD14; Langerhans and insterstitial dendritic cells also epxress CD11c

Question 31

what is CD1? what chromosome is it mapped to?

Answer 31

MHC-like molecules that present non-peptide antigens (lipids) to T cells; maps to MHC locus on chromosome 15

Question 32

what immunohistochemical staining would identify Langerhans histiocytosis?

Answer 32

CD1a; CD207

Question 33

True or False: FCeR1 is expressed on mast cells, basophils and eosinophils?

Answer 33

False; not expressed on eos

Question 34

which cell produces PGD2 when activated? and what is the function?

Answer 34

mast cells (not basos or eos); bronchocontriction; vasodilation and increased permeability; LTB4 is also unique to mast cells and is a neutrophil and T cell chemoattractant

Question 35

which cell produces PGE2 when activated?

Answer 35

eos (not basos or mast cells); opposite effect of PGD2; inhibits 5 lipoxygenase activation

Question 36

what lipid mediators are common to mast cells, basos and eos?

Answer 36

LTC4, LTD4, LTE4; also PAF; thromboxane is made by mast cells and eos, but not basos

Question 37

what is c-kit? what is its receptor? what is a pharmacologic target for this?

Answer 37

c-kit is a proto-oncogene; binds kit receptor; imatinib targets

Question 38

what are the mast cell preformed mediators

Answer 38

histamine, tryptase, chymase, carboxypeptidase, cathepsin G

Question 39

where can you find MCtc?

Answer 39

think connective tissue; skin, intestinal and respiratory SUBmucosa, conjunctiva, blood vessels, synovium

Question 40

where can you find MCt?

Answer 40

alveolar and GI mucosa

Question 41

what is the low-affinity IgE receptor?

Answer 41

FcERII; CD 23

Question 42

what allergen has been shown to cleave CD23?

Answer 42

Der-p-1; cleaves from cell surface which serves to increase the production of allergen specific IgE

Question 43

what % reduction is needed in IgE to see clinical efficacy with omalizumab? What is omalizumab?

Answer 43

96% reduction (may take many months; IgG to IgE

Question 44

describe the FCeRI complex?

Answer 44

Can exist as tetramer (a (binds the Fc portion of IgE), b and 2 y chains (main signaling component) or trimer (a and 2 y chains)

Question 45

what is a key receptor that distinguishes MCtc from MCt?

Answer 45

C5a receptor (CD88)

Question 46

what is an important growth factor for basophils?

Answer 46

IL-3 (binds to IL-3R aka CD123)

Question 47

what are the markers measured for basophil activation test?

Answer 47

CD203c; CD 63

Question 48

what is the transcription factor for eos development and what brings them to tissue?

Answer 48

GATA1; CCL-5 (Rantes) and CCL11 (eotaxin1) and CCL24 (eotaxin2)

Question 49

what factors are known to suppress eosinophilia?

Answer 49

bacterial and viral infections (except HIV), fever and steroids

Question 50

what are neutrophil attractants?

Answer 50

CXCL8 (IL8) and LTB4 (also T cell chemotaxis)

Question 51

which granules are enlarged in Chediak Higashi?

Answer 51

primary (azurophilic); contain MPO, defensins, cathelidins, cathepsin

Question 52

what aspect of platelets are targeted by antibodies in ITP? TTP?

Answer 52

GP2b3a; ADAMTS13

Question 53

what are the layers of the epidermis?

Answer 53

Basale, Spinosum, Granulosum, Lucidum, Corneum; Mnemonic: Before Signing Get Legal Counsel

Question 54

what are key cytokines secreted by epithelial cells?

Answer 54

TSLP, IL33, GM-CSF, IL-25

Question 55

what is the target antigen for pemphigus vulgaris? pemphigus foliaceous? Location?

Answer 55

IgG and IgM targeting Desmoglein 3; IgG to desmoglein 1; located in desmosome

Question 56

what is the target antigen for bullous pemphigoid, including pemphigoid gestationis?

Answer 56

IgG (linear at BMZ) to BP 230 or BP180; located in hemidesmosome

Question 57

what is the target antigen for dermatitis herpetiformis? what disease process?

Answer 57

granular IgA to transglutaminase; celiac (linear IgA is seen in IgA bullous dermatoses)

Question 58

what is the CD nomenclature, adhesion molecule location, ligand and ligand location for E-, P- and L-selectin?

Answer 58

CD62E (endothelium), P (endothelium), L (leukocytes); Ligand for E and P = sialyl lewis x on leukocytes; L selectin binds Sialyl Lewis X on GlyCam1/MadCam1 on HEVs

Question 59

what are the 3 key integrins for transmigration of leukocytes? what do they bind and where?

Answer 59

Integrins are all expressed on leukocytes; LFA1 (CD11aCD18) binds to ICAMs in endothelium; VLA4 binds to VCAMs in endothelium; A4b7 binds to MadCam1 in Gut epithelium

Question 60

what does airway smooth muscle upregulate in steroid resistant asthma?

Answer 60

glucocorticoid receptor B (inhib receptor)