Immunology Week 2

Front 1

Within the cytoplasmic compartments of:

- Endoplasmic reticulum
- Golgi complex
- Surface of B cells

Back 1

Location of antibodies

Front 2

Another location of antibodies.

These cells do not synthesize them.

Back 2

Macrophages
Natural killer cells
Mast cells

Front 3

Fc receptors

Back 3

Receptors for bidning Ab molecules

Front 4

All of the locations of antibodies?

Back 4

1. ER/Golgi/surface of B-cells
2. Immune effector cells (maccrophages, Natural killer cells, Mast cells)
3. Plasma (fluid) portion of blood and interstitial fluid of tissues
4. Secretory fluids (mucus, milk)

Front 5

During their synthesis and insertion into the Endoplasmic Reticulum, antibodies are modifed by?

Back 5

- Dissulfide bond formation
- Carbohydrate addition

Front 6

True or False:

Antibody molecules are glycolipids?

Back 6

False: they are glycoproteins

Front 7

The _____ region allows flexibility of the Ab molecule

Back 7

hinge

Front 8

The _____ region provides biological effector function

Back 8

the tail, aka Fc region

Fc = Fragment crystallizable

Front 9

This form of antibody is found primarily on resting B cells

Back 9

Membrane-bound antibody

Ig exists as part of a multisubunit complex known as the B cell receptor complex (BCR)

Front 10

This form of antibody is made by activated B cells.

Back 10

Secreted form of antibody

Front 11

These invariant proteins function in signal transduction to the interior of the cell.

Noncovalently associated with heavy chain proteins

Back 11

Ig-alpha and Ig-beta

Front 12

Signal transduction is mediated by which amino acid?

Back 12

Tyrosine.

Front 13

List the B-cell coreceptor molecules?

Back 13

CD19 (commonly used as a cell surface marker for identifying B-lymphocytes in circulation)
CR2
TAPA-1

Front 14

Is this being downregulated or upregulated?

1. Secreted IgG is able to bind Fc-gamma receptors on B-lymphocytes
2. If the antibody bound to the Fc-gamma receptor is to the same antigen as the B-cell to which it is bound, the B-cell receptor can be cross-linked with the Fc-gamma receptor on that cell.
3. Antigen-induced cross-linking of Fc-gamma and B cell receptors inhibits that particular B cells response.

Back 14

Down-regulation of B-cell activation by secreted antibody

Front 15

Myeloma proteins secreted by fully differentiated B cells (plasma cells)

Back 15

Plasmacytomas

Almost always IgG

Front 16

Light chain proteins found in the urine of patients with advanced multiple myeloma (plasmacytoma)

Back 16

Bence-Jones proteins

Front 17

A disease condition in which large quantities of a specific class of antibody is produced and found in the patient's serum

Back 17

Macroglobulinemia.

specific antibody = IgM

Front 18

Hybrid cell clones produced by the fusion of immune cells. from an immunized animal and a myeloma tumor cell line

Back 18

Hybridomas

Grows heartily in tissue culture without antigen stimulation.

Produces a single type of Ab, called monoclonal

Front 19

What two cells are used in the creation of a hybridoma?

Back 19

1. Immune cells from an immunized animal

2. Myeloma tumor cell line

Front 20

Some uses of monoclonal antibodies

Back 20

Western blots
Fat analysis
Clinical practice

Front 21

The T-cell receptor consists of a heterodimer of what two protein chians?

Back 21

TCR-alpha
TCR-beta

Linked via dissulfide bonds

Front 22

CD4 is a _____-membrane polypeptide

Back 22

trans

Front 23

CD8 is a __________ of disulfide-linked CD8alpha and CD8beta molecules

Back 23

heterodimer

Front 24

Name this process:

1. CLustering of antigen receptors allows receptor-associated kinases to phosphorylate the ITAMS

2. BLK, FYn or Lyn binds to phosphorylated ITAMS (via the SH2 domains)

3. Syk then binds, and cuases activation of:
- Phospholipase C
- Ca2+ release
- Tells cells to proliferate

Back 24

B-cell receptor cross-linking

Syk and Blk can be deficient in autoimmune disorders

Front 25

Name the part of the co-stimulatory receptor complex:

Marker for B-cells
Can be covalently linked to other proteins
Has fyn/lyn and Vav/PI-3K

Back 25

CD-19

Front 26

This molecule phosphorylates Ig-alpha and Ig-beta

Back 26

Vav

Front 27

This molecule augments the proliferation of cells

Back 27

PI-3K

Front 28

Name the part of the co-stimulatory receptor complex:

A complement receptor
Protein that can be placed on other proteins within the cell.

Back 28

Cd21

Front 29

Name the part of the co-stimulatory receptor complex:

Bind to CD21
A degradation product of CD19
Moves coreceptor complex into the receptor complex

Back 29

C3b and C3d

Front 30

____receptors tell the B-cell to halt production of antibody

Back 30

Fc

As more antibody is produced, the more likely negative feedback will occur.

Can be manipulated to prevent fetal rejection in pregnancies

Front 31

This disorder secretes myeloid proteins which wear away at bones

Dark spots appear on radiographs

Back 31

Plasmacytoma

Almost always IgG

Not autoimmune

Front 32

Name the process:

1. In the resting T-Cell, ITAMs are not phosphorylated.
2. Binding of the ligand to the receptor leads to phosphorylation of the ITAMs by CCK and FYN (receptor-associated kinases)
3. ZAP-70 binds to the phosphyrlated zeta chain ITAMS (three of them).
- ZAP-70 is phosphorylated and activated by Lck when the coreceptor (CD4 or CD8) binds to the MHC ligand

Back 32

T-cell activation

Front 33

Name the B-cell phase:

D-J rearrangement of VH variable heavy chain locus

Back 33

1. Early Pro-B cell

Front 34

Name the B-cell phase:

V-DJ rearrangement of VH variable heavy chain locus

Back 34

2. Late Pro-B cell

Front 35

Name the B-cell phase:

VDJ rearranged
Cell surface expression of heavy chain with surrogate light chain (lambda 5/ VpreB)

Back 35

3. Pre-B cell (receptor)

mechanism of allelic exclusion

Front 36

Name the B-cell phase:

B cells ceases DNA rearrangement and undergoes cell division.

Back 36

4. B-cell division

Front 37

Name the B-cell phase:

VDJ heavy chain rearranged and proven to be functional

V to J rearrangement of lambda and kappa light chain gene loci

Back 37

5. Pre-B cell

Front 38

Name the B-cell phase:

Expresses membrane IgM alone.

Negative selection of autoreactive B cells.

Back 38

6. Immature B-cell

Front 39

How long do immature B-cells last unless stimulated by foreign antigen?

Back 39

3-6 weeks.

Front 40

When introduced to foreign antigen, B-cells undergo two different processes...what are they?

Back 40

1. Isotype switching
2. Somatic hypermutation

Front 41

These cells are a major source of IgA, IgG and IgE.

Long-term production of antibody.

Interacts with Th (key point)

Back 41

Plasmablasts

Front 42

These cells are terminally differentiated, fully committed to Ab production.

No interaction with Th (key point)

Many migrate to bone and lasts for long periods of time.

Back 42

Plasma cells.

Front 43

Plasma cells need what IL in order to keep pumping out antibodies?

Back 43

IL-6

Front 44

An Recombination signal sequence on one chromosome cannot bind the same locus on the homologous chromosome.

Back 44

Main point: The V, D and J can only recombine within the same locus on the same chromosome

Front 45

What is the most common mechanism for recombination?

Back 45

Generation of an excision loop of DNA

Alters the germ-line configuration in THAT B or T cell, not the progenitor cells.

Front 46

After recombination, do introns exists at the V-D-J or V-J joints?

Back 46

No

Front 47

True/False: DNA recombination occurs to fuse the J and the C segments

Back 47

False!

NO DNA recombination occurs to fuse the J and C segments.

This occurs by splicing mRNA.

Front 48

The Recombination Signal sequences consists of three things:

1. A conserved block of 7 nucleotides
2. Nonconserved 12 or 23 bp segment
3. A conserved block of nine nucleotides.

Define each term.

Back 48

1. Heptamer
2. Spacer
3. Nonamer

Front 49

The arrangement of RSS's in the immunoglobin heavy-chain gene segments occurs (before/after) V-J joining

Back 49

Occurs before

Front 50

More emphasis:

C segments (do/do not) fuse with J segments of DNA

Back 50

Do not!

Front 51

Name the enzyme:

mediates recombination of V, D and J segments for both T and B cell antigen receptors

Back 51

Recombinase activating gene 1 and 2 (RAG1/2)

Front 52

Which enzyme is responsible for combinational diversity?

Back 52

RAG 1/2

Front 53

Name the enzyme:

Adds junctional diversity to V, D and J recombination joints for both T cell and B cell antigen receptors.

Back 53

Terminal deoxynucleotidyl transferase. (TdT)

Adds nucleotides randomly to junctions.

There is an exonuclease (not TdT) that subtracts nt's as well.

Front 54

What enzyme is repsonsible for junctional diversity?

Back 54

TdT

Front 55

Together with junctional diversity, combinational diversity, how many unique IgH genes/L are available?

Back 55

10^13 unique B cell clones are possible

Front 56

Name the process:

The surrogate light chain enables expression of successfully rearranged VDJ-IgH gene products at the cell surface, where these products can engage in signaling.

Signaling from the Pre B cell receptor results in downregulation of the RAG expression and stops IgH rearrangement.

Back 56

Allelic exclusion.

Only one IgH heavy chain allele is expressed.

The B-cell will only have one (not two) antigen specificities

Front 57

Anergy or apoptosis is used against what types of B-cells and when?

Back 57

It is used on immature B and T cells before they acquire immunocompetence.

Front 58

Why do IgM and IgD on the same B cell have identical antigen specificities?

Back 58

They have identical VH and VL domains

Front 59

Do naive B cells express SECRETED forms of IgM and IgD?

Back 59

No. Both IgM and IgD are transmembrane receptors.

Front 60

What is needed for naive B cells to secrete antibodies?

Back 60

Antigenic stimulation.

Front 61

The following events are controlled by __________ splicing:

1. Relative production of IgM and IgD

2. Relative production of transmembrane versus secreted IgM (and IgA, IgE and IgG)

3. IgD is typically not secreted under any condition.

Back 61

differential RNA splicing

Front 62

The purpose of switch recombination is to change the ________ of the heavy chain

Back 62

functionality (not the antigen specificity)

Front 63

IL-4 drives switching to Ig-___

Back 63

IgE

Front 64

Cytokines drive (idiotype/isotype/epitope) switching?

Back 64

Isotype switching.

Front 65

Transforming growth factor beta (TGFbeta) directs switching to the Ig____ isotype

Back 65

IgA

Front 66

Defined as an increase in the affinity of antibody during the progression of an immune response.

Back 66

Affinity maturation

Two types:
1. Somatic hypermutation
2. Antigenic selection of the highest affinity clones

Front 67

Mutational mechanism that introduces random mutations in the VH and VL genes

Back 67

Somatic hypermutation

Front 68

In somatic hypermutation, only mutations in the CDR1, CDR2 or CDR3 might result in a higher affinity antibody.

Back 68

These mutations are enriched by antigen-dependent selection of the highest affinity clones.

Front 69

This region provides conservation of the 3-D structure so that high variable CDR are directed to fold together

Back 69

Framework regions