Adaptive Antigen Recognition in the Immune System

Question 1

Describe the structure of a B-cell receptor.

Answer 1

Composed of a surface immunoglobulin and 2 invariant chains (IgAlpha and IgBeta)

IgAlpha and IgBeta function in signal transduction via the use of ITAMs they are attached to in the cytoplasmic side

ITAM=Immunoreceptor Tyrosine based Activation Motif

Question 2

Describe the structure of a T-0cell receptor.

Answer 2

Alpha:Beta Heterodimer

Associated proteins form the CD3 complex, which is involved in signal transduction (CD3Zeta)

Question 3

What is meant by the term Immune Repertoire?

Answer 3

One person makes more different forms of antibodies than all other proteins put together.

Question 4

Gene rearrangement events occur in the absence of antigen explains what process?

Describe this process.

Answer 4

Clonal Selection

Lymphocyte forms clones with a diverse set of receptors

Clones of mature lymphocytes become specific for many antigens

Antigen-specific clones are “selected” by antigens (Note that this shows that the lymphocytes gain diversity and specificity before ever meeting the antigen)

Antigen-specific immune response occurs after clonal expansion

Question 5

What are the 3 mechanisms by which lymphocytes gain receptor diversity? Describe each.

Answer 5

Combinatorial Diversity- Multiple germline genes. V-J or V-D-J somatic recombinations.

Junctional Diversity- Addition fo nucleotides during the process of D-J or V to DJ joining.

Somatic Hypermutation- point mutations occuring in fully assembled V-J and V-D-J regions during an immune response. Provides significant source of Ab diversity.

Question 6

How are the mechanisms of diversity for B cells/antibodies IDENTICAL to T cell receptors?

Answer 6

Production of heavy chain B cells= production of beta chain T cell

Production of light chain B cell= production of alpha chain T cell

Question 7

Somatic hypermutation does not occur in ______

Answer 7

TCRs

Question 8

Describe the process of Combinatorial Diversity.

Answer 8

V(D)J Recombinase is responsible to recombining V, D, and J segments.

Recombination activating genes (RAG1 and RAG2), only made by lymphocytes, encode for these 2 necessary components of recombinase.

Question 9

Describe the process of Junctional Diversity.

Answer 9

At the junction between D and J there is an insertion of Terminal Deoxyribonucleotidyl Transferase (TdT), which catalyzes the random polymerization of nucleotides into DNA.

P nucleotides are added to hairpins in a template manner

N nucleotides are added in a non-template manner

This leads to further diversity in the third hypervariable region (idiotype)

Question 10

The diversity generated by junctional diversity occurs in the ______ region

Answer 10

Hypervariable region

Question 11

For combinatorial diversity, what kind of cells make RAG1 and RAG2?

RAG- Recombination activating genes

Answer 11

Lymphocytes only

Question 12

What cell surface marker is CD19 specific for?

Answer 12

B cells

Question 13

What is the primary site of lymphocyte maturation?

Answer 13

Bone marrow
Thymus

Primary means antigen presentation does not occur here

Question 14

What are the 3 secondary sites of lymphocyte maturation?

Answer 14

Lymph nodes
Spleen
Peyers patches in the intestines

Question 15

What are signals from the pre-BCR responsible for?

Answer 15

Inhibit rearrangement of the Ig heavy chain on the other chromosome so an individual B cell can express one heavy chain that is encoded by only one of the two inherited alleles. This ensures that every B cell will express a single receptor, thus maintaining clonal specificity,

This is called Allelic Exclusion

Question 16

_______ deletes or inactivates cells that display antigen receptors that are self-reactive

Answer 16

Selection

Question 17

________ is acquired by immature B cells that do NOT become activated when challenged with self antigen.

Answer 17

Tolerance

Question 18

What kind of cells can undergo receptor editing to fix tolerance?

Answer 18

B cells only

T cell DO NOT undergo receptor editing

Question 19

What are are the 2 regions of the thymus?

Answer 19

Thymic cortex- outer cortical region

Medulla-inner cortical region

Question 20

In humans, thymic activity peaks during _____ and declines thereafter

Answer 20

Puberty

This is why older people get sick more often

Question 21

Where are thymocytes (immature T cells) found in the thymus?

Answer 21

Within the thymic stroma (outer cortex)

Question 22

When T cells obtain the ability to be CD4+ and CD8+ (double positive) where are they found within the thymus?

Answer 22

Medulla

Question 23

Describe the route of T cells within the body as they go from stem cells to mature T cells.

Answer 23

Stem cells within the bone marrow

Pro-T cells within the outer cortex of the thymus
Double Positive T cells within the medulla of the thymus

Mature Naive T cell in the periphery

Question 24

What is the difference between positive selection and negative selection of double positive T cells?

Answer 24

Positive selection- Recognizes self MHC/HLA and is able to mature into either CD4+ or CD8+ T cells.

Negative Selection- T lymphocytes do not become activated by self antigen. Establishment of central tolerance. Failure of positive selection leads to apoptosis.

Question 25

What is the function of Treg cells? How are they formed?

Answer 25

Function is to inhibit self-reactive helper 1 T cells in the periphery.

These are a small population of self-reactive CD4+ T cells that undergo differentiation to become Treg cells.

Question 26

What 2 surface markers do Treg cells express?

Answer 26

CD4 and CD25** on the surface

Question 27

What unique transcription factor do Treg cells express?

Answer 27

FoxP3

Question 28

Does clonal selection depend on antigens?

Answer 28

NO, clonal selection is independent of antigen

Question 29

For BCRs, describe the recombination process for both heavy and light chains.

Answer 29

Heavy (u) chain:
D-J joining
V-D-J joining
Transcription
Splicing of RNA to get Constant region next to VDJ

Light (kappa) chain:
V-J joining
Transcription
Splicing of RNA to get Constant region next to V(D)J

*Note that light chains do not have a diversity segment

Question 30

For TCRs, describe the recombination process for both chains.

Answer 30

Beta chain:
D-J joining
V-D-J joining
Transcription
Splicing of RNA to get Constant region next to VDJ

Alpha chain:
V-J joining
Transcription
Splicing of RNA to get Constant region next to V(D)J

Question 31

Compare BCR and TCR recombination.

Answer 31

Heavy chains from BCRs and Beta chains from TCRs have the same process

Light chains from BCRs and Alpha chains from TCRs have the same process

Question 32

Which cell, B or T, can undergo receptor editing if negatively selected?

Answer 32

B cells only

This gives the B cell another chance to fix its response to the antigen before it is deleted/apopstosed

Question 33

For B and T cells, which chains do not have Diversity segment?

Answer 33

B cells- Light Kappa or Lambda chains

T cells- alpha chains

Question 34

For B cells and T cells, which chains HAVE the Diversity segment?

Answer 34

B cells- Heavy chain

T cells- Beta chains