Immuno Week 4 / Day 1

Front 1

Factors stimulating Th1 development

Back 1

IL-12 by dendritic cells, influences IFN-gamma production by NK cells

Front 2

Transcription factor for Th1 cells

Back 2

TBet

Front 3

Tbet turns on expression of what genes

Back 3

IFN-gamma

Front 4

Th1 cells secrete what

Back 4

IL-2

IFN-gamma

Front 5

Pathogenstrigger tissue macrophages or DCs to secrete...

Back 5

IL-1 and TNF-alpha

Front 6

What do IL-1 and TNF-alpha do

Back 6

Upregulate E- and P-selectin

Upregulate ICAM-1 and VLA-4 on endothelial cells which line the blood vessel

Front 7

What is the purpose of upregulation of selectins and LFA-1 ligands?

Back 7

"Mark" the infected territory

Front 8

Purpose of chemokines

Front 9

CD4 effector cells

Production of TNF-alpha, IFN-gamma, and TNF-beta does what

Back 9

Activates macrophages

Front 10

CD4 effector cells

Production of TNF-alpha and CCL-2 does what

Back 10

Activate endothelial cells

Front 11

CD4 effector cells

Production of IL-3 and GM-CSF

Back 11

Act on Progenitor Cells in marrow

Increases Numbers of Macrophages / Dendritic Cells

Front 12

Co-stimulatory molecule in CD4 - macrophage interaction

Back 12

CD40 / CD40L

Front 13

Th1 cells secrete what to activate macrophages

Back 13

IFN-gamma

Front 14

Consequences of macrophage activation

Back 14

1. Phagosome fusion with lysosome efficiency increased

2. Increased levels of lysosomal enzymes

3. Increase in antimicrobial molecules

Front 15

ChronicGranulomatous Disease caused by mutations in ___________

Causes ___________

Back 15

NADPH proteins

Inability to clear pathogens, chronic stimulation of T cells --> granulomas

Front 16

Enzyme used by foreign organisms to degrade superoxide radicals

Back 16

Catalase

Front 17

Ligand halting immune response

Back 17

CTLA-4

Front 18

Two major ways memory T cells differ from naive T cells

Back 18

Memory cells circulate, naive in lymph nodes

Memory have less stringent activation requirements

Front 19

In an adult what percentage of T cells are memory

Back 19

About 50%

Front 20

Two types of T Memory cells

Back 20

Effector Memory and Central Memory

Front 21

Major CDs for T cell homing to lymph nodes

Back 21

CD62L, CCR7

Front 22

Effector memory T cells

Back 22

CD62L/CCR7 negative

Circulate in tissues

When stimulated by antigen, differentiate into effector secreting IFN-gamma, I-4, IL-5

Front 23

Central memory T cells

Back 23

CD62L/CCR7 positive

Upon stimulation, express CD40L

Help B cells

Front 24

Differences in expressed surface molecules between TM and TE/TN

Back 24

Decreased CD62L / CCR7

Increased CD44

CD45RO vs CD45RA (naive)

Increased bcl-2

Increased CD127

Front 25

What is bcl-2

Back 25

Prevents apoptosis

Front 26

Difference between CD45RO and RA

Back 26

CD45RO more closely associated with CD4 or 8

RO has phosphatase which removes the phosphate on CD 4/8 keeping lck from being activated

Front 27

Cytokines involved in T memory cell proliferation without presence of antigen

Back 27

IL-7, IL-15

Front 28

Transcription factor for differentiation into TReg

Back 28

FoxP3

Front 29

TReg receptor for IL-2

Back 29

CD25

Front 30

Molecules identified on the surface(or secreted) of TRegcells associated with effectorfunctions

Back 30

CTLA-4, TGF-beta, IL-10

Front 31

Defect in FoxP3 causes

Back 31

lethal autoimmunity

Front 32

Gamma/delta T cells express receptors depending on

Back 32

What compartment they're in

Front 33

Vγδ1 receptor recognizes

Back 33

MIC-A and MIC-B

Front 34

Do NK cells have TCRs?

Back 34

No

Front 35

What antigens do NK cells recognize

Back 35

Viral, MIC-A, MIC-B

Front 36

What antigens do NKT cells recognize

Back 36

Lipids presented on CD1d

Front 37

What antigens does Vγ9Vδ2 recognize

Back 37

Metabolic products of invaders

Front 38

Do NK rearrange immunoglobulin genes or receptor genes?

Back 38

No

Front 39

Defining cell surface protein of NK cells

Back 39

CD56

Low expression predominate in blood

High expression in lymphoid tissue

Front 40

How are NK cells different from Tcells?

Back 40

Larger

Have granules (immediate readiness)

NO TCR

No memory response

Front 41

Virally-infected cells produce _________ which starts NK cell proliferation

Back 41

IFN-a and IFN-b

Front 42

People who lack NK cells suffer from persistent

Back 42

viral infections, especially herpes

Front 43

Macrophages activate NK cells by producing

Back 43

IL-12

TNF-a

IL-15

Front 44

Major function of NK-secreted IFN-gamma

Back 44

activate TBET transcription factor in CD4 cells

Front 45

Positive feedback system between NK cells and macrophages

Back 45

NK cells --> IFN-gamma

Macrophages --> IL-12

Front 46

TNF-a induces

Back 46

inflammation

Front 47

NK cell receptor that binds to MIC-A and MIC-B

Back 47

NKG2D

Front 48

Two structural types of NK receptors

Back 48

Immunoglobulin-like and lectin-like

Front 49

What are MIC-A and MIC-B

Back 49

Cell surface proteins produced in response to stress

Front 50

Inhibitory signals to NK cells delivered by

Back 50

HLA-E

HLA-A, B, C

Front 51

What NK receptor recognizes HLA-E

Back 51

CD94:NKG2A

Front 52

HLA-E binds to what

Back 52

Degraded leader peptides of HLA-A, B, and C heavy chains

Front 53

The amount of HLA-E on a cell surface is indicative of

Back 53

The amount of HLA-A, B, and C being made by the cell

Front 54

Do all NK cells have the same KIRs

Back 54

No, each NK cell expresses a random subset of KIR genes, creastes enormous diversity

Front 55

KIRs recognize what

Back 55

Polymorphic determinants on HLA-A, B, and C

Front 56

Is the absence of a negative signal enough to stimulate an NK cell

Back 56

No, needs to have a positive signal

Front 57

What does CD1 do

Back 57

Presents lipid antigens produced by organisms such as mycobacteria

In the absense of these, self lipids

Front 58

What cells express CD1

Back 58

Cells that can be infected with mycobacteria ie dendritic cells

Front 59

What cells express CD1d

Back 59

Epithelial cells in many tissues

Front 60

CD1d presents antigen to

Back 60

NKT cells

Front 61

What receptors do NKT cells have

Back 61

a:b TCR and NK receptors

Front 62

Mismatchedbone marrow cell transplants are a problem because

Back 62

They are allogeneic cells which by definition can express different MHC class I molecules

Get attacked by NK cells

Front 63

NK cells can recognize and kill human cells coated with

Back 63

IgG1 or IgG3

Front 64

Why can antibody-dependent cell-mediated cytotoxicity (ADCC) only occur at a late stage in the primary immune response?

Back 64

Because class-switching to IgG must occur. Faster in secondary responses.

Front 65

NK receptor for FC portion of IgG1 and IgG3

Back 65

FcγRIII (CD16)

Front 66

Placental NK cells

Back 66

Trophoblasts secrete HLA-E, induces NK cells to produce factors that promote vessel growth in placenta

Front 67

Where are B lymphocytes formed

Back 67

Fetal: liver and spleen

Adult: Bone marrow

Front 68

Half life of a B cell

Back 68

3-8 weeks

Front 69

Cells with the potential of becoming a B or T lymphocyte

Back 69

Common lymphoid progenitor CLP

Front 70

Main event of Pro-B stage

Back 70

Rearrangement of heavy chain genes

Front 71

A B cell is "early pre-B" once it expresses

Back 71

Mu heavy chain

Front 72

How many times can a pro-B cell rearrange its heavy chain?

Back 72

Twice - each has two copies of the heavy chain locus, one inherited from mom and one from dad.

If both nonproductive, cell dies

Front 73

Genes involved in heavy chain rearrangements

Back 73

RAG1 and RAG2

Front 74

Two criteria a B cell must satisfy to survive

Back 74

Makes a functional mu heavy chain

Heavy chain must combine with a light chain

Front 75

How are B cell heavy chains tested?

Back 75

VpreB and lambda-5 bind to the heavy chain in similar manner to light chains

"Pre-B cell receptor"

Front 76

Assembly of a heavy chain + surrogate light chain causes expression of what to stop

Back 76

RAG enzymes

Front 77

When do RAG enzymes reappear in B cell development

Back 77

Late pre-B

Front 78

Key growth factors for B cells expressed by stromal cells

Back 78

IL-7 (IL-7R)

Stem Cell Factor (ckit, receptor gone when Pre BCR comes)

Front 79

Immature B cells express what on their surface

Back 79

IgM

Front 80

As B cells mature what do they display on their surface

Back 80

IgM and IgD

Front 81

How do developing B cells deal with sensitivity to self-antigen?

Back 81

1. If strong specificity, apoptosis

2. If moderate sensitivity, rearranges light chain (receptor editing)

Front 82

What surface protein defines B1 cells

Back 82

CD5

Front 83

B1 cells mostly produced during the _____ period

Back 83

fetal

Front 84

B1 cells in adults mostly found where

Back 84

Peritoneal and pleural cavities

Front 85

B1 cells detect what

Back 85

PAMPs, poor specificity for proteins

Front 86

B1 cells are a major source for what disease

Back 86

CLL bc constant renewal can lead to genetic error

Front 87

Where are marginal zone b cells found

Back 87

Marginal sinus of white pulp in spleen

Front 88

What surface receptors are on MZ b cells

Back 88

CD21/35

C3 fragment complement receptors

Front 89

Splenectomy patients lack what population of B cells

Back 89

Marginal zone

Front 90

MZ b cells have a biased BCR repertoire to

Back 90

common environmental bloodborne antigens

Front 91

Where are T cell progenitors produced

Back 91

Fetal: Liver --> thymus in 8-9 wk gestation

Neonate: Bone marrow --> thymus

Front 92

Definitive surface markers of T cells

Back 92

TCR, CD3

Front 93

Regions of thymus

Back 93

Subscapular: committment

Cortex: TCR positive/negative selection

Medulla: Negative selection, maturation

Front 94

DiGeorge syndrome

Back 94

Thymic aplasia

Defect in neural crest

Suboptimal to absent production of T cells

Front 95

Percentage of T cells that are

DN

DP

SP

Back 95

DN: 5%

DP: 80%

SP: 15%

Front 96

Developing T cells are DN in what thymus region

Back 96

subcapsular (7-14 days)

Front 97

Developing T cells are DP in what thymus region

Back 97

Cortex and cortico-medullary junction (4 days)

Front 98

Developing T cells are SP in what thymus region

Back 98

Medulla (7 days)

Front 99

What can be used to stage developing T cells

Back 99

CD4 / CD 8 expression

Front 100

Critical cytokine in T cell development

Back 100

IL-7, turns on RAG

Front 101

Commitment to alpha-beta chain lineage requires _______ rearrangement whereas gamma-delta requires _______

Back 101

one; two

Front 102

TCRg/d T cells found mainly in

Back 102

Epithelial cell surfaces, GI, reproductive tracts

Front 103

What happens after successful rearrangement of the beta chain of T cells

Back 103

Suppression of RAG

Proliferation to DP thymocytes

Front 104

X-SCID is due to

Back 104

Failed IL-7 signaling during development --> no T

Failed IL-4 and IL-21 --> no B cell class switching

Front 105

Treatment of XSCID

Back 105

Bone marrow transplant

Gene therapy

Front 106

What is positive selection in relation to T cells

Back 106

Permitting survival of T cells that can recognize self-MHC

Front 107

What is negative selection in relation to T cells

Back 107

•Eliminates T cells that react too strongly with self-MHC molecules and self-antigen presented by self-MHC.

Front 108

Factor that suppresses CD8 production on an MHC-II recognizing T cell

Back 108

Th-PoK

Front 109

Factor that suppresses CD4 production on an MHC-I recognizing T cell

Back 109

Runx3

Front 110

Negative selection of T cells mostly mediated by

Back 110

Dendritic cells and macrophages presenting self-antigens

Front 111

Cells expressing proteins from other tissues to show to developing T cells

Back 111

Thymic medullaryepithelial cells that express autoimmune regulator (AIRE)

Front 112

Surface factors of Effector CTL cells

Back 112

Reduced CD62L

Presence of ICAM-1 and VLA-1

Increased CD2

Front 113

Cytotoxic T cells produce mainly

Back 113

cytotoxins

Front 114

_______ are the most effective APCpopulation for delivering signals to activate naïve CD8 T cells.

Back 114

Dendritic cells

Front 115

Signal 1 and signal 2 for naive CD8 cells

Back 115

TCR - MHC:peptide

CD28 - B7

Front 116

How do CD4 Th1 cells help CD8 cells?

Back 116

Increase expression of B7 on APCs

Production of IL-2

Front 117

Lytic granules of cytotoxic cells

Back 117

Granzymes, perforin and granulysin

Front 118

Granzyme pathway of destruction

Back 118

Cd8 cells release contents of lytic granules (perforin and granzymes form a multimeric complex with serglycin and granulysin).

Poresare generated in target cell membrane.

Granzymes,perforin, granulysin (human) enter target cell.

Thecytotoxic cell disengages.

Front 119

Necrosis v Apoptosis

Back 119

Necrosis: No DNA fragmentation, leakage of cell contents, inflammation

Apoptosis: DNA cleavage, plasma membrane blebbing

Front 120

How is DNA cleaved in granzyme pathway

Back 120

Granzyme activates caspase 3 --> cleavage of ICAD inhibitor of CAD (Caspase Activatable DNAase)

Front 121

Targets of caspase 3

Back 121

Cleave and disable inhibitor of Caspase Activatable DNAase (ICAD)

Inhibit lamin proteins (cell integrity)

Inhibit nuclear repair enzymes

Front 122

Mitochrondria in apoptosis

Back 122

Swell and leak cytochrome c --> bind to APAF --> activation of pro-caspase 9+3 --> cleavage of ICAD

Front 123

Bax, Bok, Bak

Back 123

Form pores in mitrochondria

Front 124

Bad, bid, puma

Back 124

Inhibit bcl

Front 125

BcLs

Back 125

Inhibit apoptosis

Front 126

Two death pathways of CTLs

Back 126

1.Perforin / Granzyme exocytosis pathway

2.Death Ligand – Death Receptor Pathways

Front 127

What is the FasL-Fas pathway

Back 127

Fas ligand binds to Fas, causes conformational change in death domains inside cell. FADD binds to DDs, recruits caspases 8 and 3. Caspase 3 cleaves ICAD.

Front 128

Homotryptic dimer initiating an apoptotic pathway

Back 128

Fas

Front 129

Fas-FasL pathway most important for

Back 129

controlling proliferation of lymphocytes