Generation of Lymphocyte Antigen Receptors

Question 1

Where do T & B Lymphocytes Develop?

Answer 1

B cells leave bone marrow as immature cells

T cells move from bone marrow to the thymus where they mature and then leave

Question 2

What do the antigen receptors of B and T cells do?

Answer 2

1. Bind epitopes in a highly specific manner

2. Trigger responses in the lymphocytes in which they are expressed.

Question 3

B cell receptors bind what kind of chemical isotopes?

Answer 3

B cell receptors bind non-degraded antigens of many types (proteins, lipids, carbohydrates, nucleic acids, etc.)

Question 4

T cell receptors bind what kind of chemical isotopes?

Answer 4

T cell receptors bind complexes of MHC molecules and peptides (degraded proteins)

Question 5

The antigen receptors require additional components to do what?

Answer 5

transmit signals to the interior of the cell

Question 6

The antigen receptors of lymphocytes have variable and constant domains that do different things what are they?

Answer 6

variable domains that form the antigen binding site and constant domains that maintain overall structure.

Question 7

Are immunoglobulins membrane bound or secreted?

Answer 7

can be BOTH

Question 8

Immunoglobulins are made of what kind of chains that recognize antigens?

Answer 8

variable heavy and light chains

Question 9

T cell receptors are made of what kind of chains that recognize antigens?

Answer 9

variable regions of alpha and beta chains

Question 10

What is the structure of IgG Ab?

Answer 10

Fab region and Fc region

• There are 5 different classes (isotypes) that are functionally different due to constant region differences
• light chains are either kappa or lambda (does not change during class switching)

Question 11

What are the Major Isotypes (Classes) of Antibodies?

Answer 11

IgA, IgD, IgE, IgG and IgM

Question 12

EACH IMMUNOGLOBULIN VARIABLE REGION (HEAVY AND LIGHT CHAIN) HAS 3 REGIONS OF HYPERVARIABILITY THESE ARE CONTACT SITES FOR what?

Answer 12

THE EPITOPE IN THE ANTIGEN BINDING SITE

Question 13

What are the functions of the major classes of Ab?

Answer 13

IgA: mucosal immunity
IgD: naive B cell
IgE: mast cell activation and defense against parasites
IgG: opsonization, completment, ADCC, neonatal immunity
IgM: naive b cell and completment

Question 14

What are allotypic Ab differences?

Answer 14

a difference in the constant region of the heavy chain of Ab that usually only differs by one AA within an isotype

Question 15

What is an idiotypic Ab difference?

Answer 15

difference in variable region that dictates specificity

Question 16

What is the difference between affinity and avidity?

Answer 16

affinity is the strength of a single binding interaction

avidity is multiple binding interactions eg: MHC needed the costimulatory interaction as well

Question 17

What are some important features of TCRs?

Answer 17

made of alpha and beta chains

use AA chains bound to MHC and affinity does not change

CD4 or CD8 simultaneously bind MHC

Question 18

What are some important features of Ig (aka B cell receptors)?

Answer 18

made of heavy and light chains

bind macromolecules and small chemicals and affinity increases throughout immune response

Question 19

How is receptor diversity generated?

Answer 19

1. COMBINATORIAL (MULTIPLE GENE SEGMENTS; VDJ)
2. JUNCTIONAL DIVERSITY
3. MIX AND MATCH PAIRING OF LIGHT AND HEAVY CHAINS
4. SOMATIC HYPERMUTATION *

Question 20

What are the three gene segments that recombine during cellular differentiation and maturation?

Answer 20

The first recombination event is the heavy chain D and J followed by recombination of V with DJ. VDJ then recombines with a constant region gene segment.

Then V and J then recombine and VJ recombine with a C segment to form a transcript for the light chain. light chain (or TCR alpha) then binds to heavy chain (or TCR beta)

Question 21

Which cells have a greater diversity of receptors?

Answer 21

TCR > Ig

Question 22

What is allelic Exclusion?

Answer 22

first heavy chain recombination event occurs on the maternal chromosome and is successful, the heavy chain genes on the paternal chromosome will not rearrange, and the cell will express the maternal gene product only. If the first rearrangement is not successful, rearrangement of the heavy chain genes on the paternal chromosome will occur. If successful, the paternal heavy chain gene product will be expressed. If neither is successful, the cell will die.

Question 23

If Mutations in the Recombination Enzymes (VDJ recombinase) occurs what disease do you see?

Answer 23

autosomal SCID!

Question 24

Steps in the Maturation of Lymphocytes:

Answer 24

Pro B/T cell needs to express on chain of antigen receptor (1st checkpoint) then expresses full antigen receptor (2nd checkpoint) then tested for self recognition

Question 25

Mature B cells express what two forms of Ig?

Answer 25

mature have IgM and IgD

activated* B cells lose the IgD

Question 26

As these have the potential for causing autoimmune pathology, B cells with autoreactive receptors must be removed or functionally inactivated. This process is known as what?

Answer 26

negative selection

Question 27

Steps in maturation of T-cells?

Answer 27

Thymus is major site of maturation. Positive selection is reaction with MHC complexes then negative selection occurs if the cell recognizes self peptide within an MHC.

Question 28

What are double positive T cells?

Answer 28

immature T cells expressing both CD4 and CD8 will undergo selection and then lose the CD molecule that wasn’t selected

Question 29

All lymphoid neoplasms are derived from what?

Answer 29

single cells and are thereby clonal

Question 30

clonal malignant B or T cells can be identified by their what?

Answer 30

unique antigen receptors

Question 31

Clonal malignant cells can be identified in patients by analyzing the antigen receptor what?

Answer 31

genes in T or B lymphocytes. If a large population of clonal cells is present, this information can be used to differentiate clonal neoplasms from polyclonal pathologic processes