I And I B And T Cell Development

Front 1

What is the order of B cell development?

Back 1

Pro B cell --> Pre B cell (large, then small) --> Immature B cell -->Mature Naive B Cell

Front 2

_ drives the maturation process of B cells, it is required for maturation

Back 2

IL-7

Front 3

Stromal cells are located in the _, interact directly with _ cells, and are responsible for the secretion of _, most importantly being _

Back 3

bone marrow;
Pro and Pre B cells
cytokines, such as IL-7

Front 4

On a molecular level, the early pro B cell is undergoing what gene rearrangements?

What about in the late pro B cell?

Back 4

Heavy chain Dh to Jh rearrangement


Then, Vh to DhJh rearrangment. Once the VDJ are next to eachother, this is called a pre B cell

Front 5

At the pre B cell stage, the B cell begins to express a _ chain

Back 5

mu

This is associated with a surrogate light chain molecule and the Igalpha and Igbeta polypeptides.

Front 6

When the mu chain and surrogate light chains reach the cell surface of the pre B cell, the cell will do what?

Back 6

halt any more rearrangement of the heavy chain genes, the cell will begin rearrangment of light chain genes.

Production of surrogate light chains will cease and thus the pre b cell receptor disappears

Front 7

_(#) light chain isotype(s) is expressed on the membrane of a B cell

What are they?

Back 7

one

either Kappa or Lambda....NOT both.

Front 8

Immature B cells express _ on the cell surface

Back 8

IgM (either mu/kappa or mu/lambda)

Front 9

The pre B cell will first rearrange the _ gene on it's first chromosome, if that doesn't work it will try _ on it's second. If neither of these are successful it will go back to the first chromosome and _, then _ on the 2nd

Back 9

kappa light chain gene, kappa

lambda, lambda

If these aren't successful, the cell will undergo apoptosis

Front 10

The early mature B-cells express low levels of _

Back 10

IgD; they have coexpression of IgD and IgM

These cells are the exported from the bone marrow to the lymphoid organs where IgD expression increases

Front 11

B1 cells are characterized by expression of _ on the cell's surface.

Back 11

CD5

Front 12

Rearranged heavy chain genes in B1 cells are less diverse, Therefore, antibodies produced by these cells are _, and _

Back 12

Low affinity
Binds to many different antigens (polyspecificity)

Front 13

T/F B1 cells are continuously made in the bone marrow throughout the life span

Back 13

False.

With time, B1 cells are no longer developed in the bone marrow, In adults, B1 cells are maintained through cell replication in the peripheral circulation. They are often the source for B cell tumors due to their ability for self renewal

Front 14

A mature, naive B cell becomes activated by an _

Back 14

antigen specific CD4 T helper cell (2)

Front 15

Plasma cells are the last step in _ cell development. They are _ and cease to _.

Back 15

B Cell; terminally differentiated and cease to divide

Front 16

(T/F) Plasma cells are the last phase of B cell development and therefore fully express cell surface immunoglobulins and MHCII molecules

Back 16

FALSE

They DO NOT express cell surface igs or MHCII molecules

Front 17

(T/F) Plasma cells can respond to antigens and present them to the T cell

Back 17

FALSE! They do not express cell surface Igs, and therefore cannot respond to antigens or interact with T cells

Front 18

There are two lineages of T cells, what are they?

Back 18

alpha beta (more common) and gamma delta

Front 19

Thymocytes originate from _, and migrate to the _ to become mature

Back 19

bone marrow stem cells

thymus

Front 20

T cell receptors are composed of 2 different polypeptide chains, what are they?

Back 20

variable region and constant region

Front 21

Progenitor T cells enter the thymus and interact with _ cells, who express _

Back 21

thymic stromal cells, who express t cell specific adhesion molecule CD2.

At this point, the progenitor cells do not express TCR complex or co receptors (CD4 and 8). As a result, They are called double negative cells

Front 22

Double negative thymocytes express _ and then _.

After they slow expression of the first, what happens ?

Back 22

CD 44, and then CD 25

Once expression of CD44 decreases, TCR genes begin to rearrange.

Front 23

If a productive β chain is rearranged first, the β chain is assembled with a _

Back 23

surrogate α chain (pTα) , forming a pre T cell receptor

After this, gene rearrangement is halted, and then restarted using only alpha, gamma, and delta loci

Front 24

Pre-T cell receptor induces the development of the precursor T-cells to _

Back 24

the “double positive” phase

this is when t cells express both CD4 and CD8

Front 25

What is special about CD3 T cells?

Back 25

They are of gamma delta rearrangment

Front 26

T cells undergo positive and negative selection.
Positive selection is critical in determining _ (other than survival of thymocytes whose TCRs recognize antigens bound to self)

Back 26

whether a double-positive T-cell will become a CD4 or a CD8 cell

Front 27

With MHCI, the thymocyte becomes _
With MHCII, the thymocyte becomes _

Back 27

CD8

CD4

Front 28

An Ig Isotype is _

An Ig allotype is _

An Ig idiotype is _

Back 28

An isotype is a classification of different immunoglobulin molecules based mainly on amino acid sequence. (ie. IgE vs IgA)

Allotypes are identifiable allelic variations in the constant regions of the heavy or light chain genes.

- Idiotype refers to unique features of the antigen binding site (comprising both H and L chain variable regions) that determine the antigen specificity of a given Ig molecule.

Front 29

What are the three major functions of the Antibodies?

Back 29

Neutralization, Opsonization, Complement Activation

Front 30

Neutralization is performed mostly by what antibodies?

Sensitization of mast cells is performed by what Ab?

What Abs function to activate the complement system?

Back 30

IgG and IgA (to a lesser extent, IgM)

Mostly IgE, and a little bit of IgG1 and IgG3

IgM, IgG3, and a little bit of IgG1, IgG2, and IgA

Front 31

What Ab's function to Opsonize Antigens?

Back 31

Mostly IgG1, and to a lesser extent, IgG3, IgG4, and IgA

Front 32

IgG is mostly distributed where?

What about IgA?

Back 32

Diffused into extravascular sites;

It's transported across the epithelium?

Front 33

The hypervariable region of the H- and L-chains are brought together to form a hypervariable surface which is the _

Back 33

antigen binding site.

Front 34

An _ is a small chemical complex (relative to the size of the macromolecule or cell of which it is a part) that determines the specificity of an antigen-Ab interaction. Aka, antigenic determinant.

Back 34

epitope

Front 35

Regarding the light chains in B cells, . The 1st and 2nd hypervariable regions are completely within the V segment and the 3rd hypervariable region is determined by _

Back 35

the junction between V and J segments.

Front 36

_ can be secreted or membrane bound, but _ is only found as a membrane bound form.

Back 36

IgM

IgD

Front 37

_ occurs in B cells at the time of initial activation with antigen

Back 37

Ig Class Switching

Front 38

In Ig Isotype switching, _remains the same, whereas, the _ is changed.

Back 38

Antigen specificity

effector function

Front 39

_ occurs in mature B cells in secondary lymphoid organs following B cell activation by a T dependent antigen

Back 39

somatic hypermutation

Front 40

The TCR requires help from four invariant membrane proteins in order to be _.

These proteins include the CD3 complex (3) and the zeta chain

Back 40

to be transported from the ER to the cell surface.

Without CD3, the TCR cannot be transported to the plasma membrane, and is eventually degraded.

Front 41

DNA rearrangement within the a-chain locus will result in deletion of the _ locus

Back 41

d-chain locus.

this is because the delta locus is located within the alpha chain locus, between Valpha and J alpha genes

Front 42

In comparing TCR and Ig,
TCR loci have fewer _, TCR genes show greater _, they do not exhibit _, and do not undergo _.

Back 42

V segments; junctional diversity, somatic hypermutations, isotype switching.

Front 43

_has the greatest influence on success or failure of transplants.

Back 43

MHC also called HLA, Huma Leukocytic Antigen, although this term is human specific and MHC is not

Front 44

MHC Class I molecules are involved in the regulation of _ cell function

Back 44

NK

Front 45

NK cells kill_ and _, bc the expression of MHC I is altered

Back 45

tumor cells that cells that are infected in viruses

Front 46

MHC Class II presents antigen to _ cells.

MHC Class I presents antigen to _ cells

Back 46

CD4

CD8

Front 47

In the MHC I molecules, the Peptide binding groove is formed by the _ and _ domain,_ is the only one that has a transmembrane domain; it is also the domain that binds to the _

Back 47

alpha 1 and alpha 2

alpha 3; binds to CD8 co receptor

MHC class I has heavy and light chains (alpha and beta

Front 48

MHC Class II structure has _ and _ domains, no _.

The _ domain binds to the CD4 co receptor

Back 48

2 alpha and 2 beta, no heavy or light

Beta 2 binds to the CD4.

Front 49

MHC Class _ accomodates smaller peptides, whereas MHC CLass _ accomodates peptides of 10-30 residues, and allows for the peptide to flow beyond the groove

Back 49

MHC Class I

MHC Class II

Front 50

Class I MHC is expressed on _ cells

Class II MHC is expressed on _

Back 50

all nucleated cells,

antigen presenting cells and activated T cells

MHC CLASS I IS MORE PREVALENT

Front 51

Important Isotypes for MHC Class I are _, for MHC Class II they are _

Back 51

ABC (highly polymorphic, present Ag to CD8 cells, form ligand for NK cells)

PQR (highly polymorphic, directly present to CD4 cells)

Front 52

MHC gene complex is found on what chromosome?

Back 52

Short arm of Chromosome 6

Front 53

Expression of almost all the MHC II molecules is under the influence of _, (which is produced by _cells)

Back 53

IFN-gamma

CD4 TH1 (during adaptive response), and NK cells (during innate response)

Front 54

Absence of CIITA causes _ due to _

Back 54

severe immunodeficiency due to nonproduction of MHC Class II molecules and lack of CD4 function

Front 55

Polymorphism of HLA-DR is almost entirely by _contribution

Back 55

b chain

Front 56

_ is when a small fragment of one HLA allele is replaced by a similar gene…ie the homologous section of another allele within the same gene.
_ is when this recombination event involve 2 separate genes.

Back 56

Interallelic conversion or segmental exchange

Gene conversion

Front 57

The _is responsible for the variability found in the MHC molecule

Back 57

Peptide binding group

Front 58

A set of anchor residues that determine the binding of peptides to a particular MHC isoform is called _

Back 58

peptide-binding motif.

Front 59

What does the T cell recognize?

Back 59

Peptide-MHC Complex

Front 60

This restriction in antigen specificity of T cells due to MHC is called _

Back 60

MHC-restriction

Front 61

(t/f) In the absence of infection, all MHC molecules still contain peptides

Back 61

true!

Front 62

MHC molecules bind peptides via_ on the peptide

Back 62

“anchor residues”

Front 63

T cells that respond to complex of peptide and allogenic MHC molecules are called _ cells

Back 63

alloreactive T cells.

Alloreactivity is a common problem in case of organ transplantation.

Front 64

T cell recognizes _

Back 64

processed peptides,

Front 65

Super antigen binds to the _ region of TCR and to the _

Back 65

Variable beta region, and to the outer surface of MHC class II

Ex: Toxic Shock Syndrome of staphylococcus

Front 66

What type of T cells fight infections?

Back 66

alpha beta

Front 67

CD8 cells fight _ infections such as _, they are also called _

Back 67

intracellular (viral), cytotoxic T cell

Front 68

CD 4 cells fight _ infection. They are AKA _.
2 types:
TH1 cells activate _
TH2 cells stimulate _

Back 68

extracellular; T helper cells.

activate tissue macrophages and CTLs to phagocytose and kill extracellular pathogens

TH2 stimulate B lymphocytes to differentiate into plasma cells make antibodies

Front 69

Plasma cells are _ prominent,

Back 69

golgi (bc it is a secretory cell)

Front 70

CD4+ and CD8+ T cells preferentially recognize antigens sampled from the _ and _ pools, respectively

Back 70

extracellular and cytosolic

Front 71

_ are small chemicals that fail to induce an immune response, this is due to lack of size and complexity

Back 71

haptens

Front 72

Soluble peptides will be recognized by CD4 cells (T/F)

Back 72

False.

They must be in the context of antigen presenting epitopes

Front 73

effector T cells activate _ and _by production of cytokines and by expressing surface molecules

Back 73

macrophages (TH1) and B (TH2) lymphocytes

Front 74

Different antigen presenting cells have different outcomes. For example:
Dendritic cells produce_
Macrophages produce _ and _
B cells produce _ and _

Back 74

Dendritic cells only produce effector T cells

Macrophages produce effector T cells, but also become activated themselves

B cells activate effector T cells, and differentiate into plasma cells

Front 75

Tissue born antigen generates immune response in_ When it is blood born this is in the _

Back 75

lymph nodes.

spleen

Front 76

primary follicles are _, secondary follicles are _

Back 76

naive B cells, activated B cells

Front 77

Langerhan cells are _ found in the _

Back 77

dendritic cells found in the subcutaneous tissue

Front 78

Dendritic cells come from _ precursors

Back 78

myeloid

Front 79

In all cells, cytosolic proteins are degraded by a large protein complex called the _

Back 79

proteosome

Front 80

Regarding MHC Class I molecules, Peptide fragments are transported across the endoplasmic reticular membrane by another protein, embedded in the membrane, called_

Back 80

Transporter associated with Antigen Processing (TAP).

The peptides are usually 8-10 amino acids long

Front 81

Peptides presented by MHC class I molecules are generated in the _

Back 81

cytosol

Front 82

Newly synthesized MHC class I molecules and b2 microglobulin are translocated to the _

Back 82

endoplasmic reticulum (ER).

(Here they complete their folding and load peptide, which is aided by proteins known as chaperones.)

After leaving the ER, the MHC is in a membrane bound vesicle

Front 83

On entering ER, MHC I molecules bind a membrane protein, _. This protein stabilizes the class I heavy chain until beta2 microglobulin binds.

Back 83

clanexin

Front 84

Defficiency of _ cause a rare disease called bare lymphocyte syndrome.

Back 84

TAP protein


which binds the heavy chain of MHC Class I during development

Front 85

Class II molecules bind peptides derived from _

Back 85

extracellular sources .

They are internalized, forming intracellular vesicles. Eventually, these become acidifies due to proton pumps, which will break down the vesicle contents to generate peptides. The vesicle then fuses with MHC class II molecules

Front 86

_ blocks binding of peptides to MHC class II in vesicles.

_ facilitates the release of the above molecule allowing peptides to bind

Back 86

CLIP

HLA-DM

in other words, Peptide loading is facilitated by HLA-DM

Front 87

What is the source of protein antigens for Class II MHC molecules?

Class I?

Back 87

Endosomal/lysosomal proteins, mostly internalized from extracellular environment

Cytosolic proteins, mostly synthesized in the cell, may enter cytosal from phagosomes

Front 88

TAP in the ER is involved with Class (I or II) MHC pathway?

HLA-DM is involved in Class (I or II) MHC pathway?

Back 88

Class I

Class II

Front 89

Class I MHC - (extracellular/intracellular)

Class II MHC - (extracellular/intracellular)

Back 89

Intracellular

Extracellular