(Section B: Immunology) Lecture 13: T-Cell Immunity I

Question 1

What theory did Paul Erhlich come up with?

Answer 1

Side Chain Theory

Question 2

What lymphatic organ did Jacques Miller research in 1960?

Answer 2

Thymus

Question 3

What did the removal of the thymus have on mice?

Answer 3

• Could no longer make antibodies in response to immunization
• Could longer immunologically reject a skin graft

Question 4

What were cells produced by the thymus called?

Answer 4

T Cells
* “T” for “thymus”

Question 5

What lymphatic organ did Max Cooper research in 1965?

Answer 5

Bursa of Fabricius in birds

Question 6

What effects did the removal of the Bursa of Fabricius have on chickens?

Answer 6

• Could not produce antibodies
• Could still reject skin grafts

Question 7

What cells did the Bursa of Fabricius produce?

Answer 7

B Cells
* “B” for “bursa”

Question 8

Where are B cells produced in mammals?

Answer 8

Bone marrow (“B” for “bone marrow”)
* Area rich in cytokines, growth factors, HSC, endothelial cells etc

Question 9

How do B Cells and T Cells look?

Answer 9

They look similar to each other

Question 10

What types of T and B Cells are there?

Answer 10

• T helper cells (Th)
• T cytotoxic cells (Tc)
• B cells

Question 11

What are the cell receptors for T and B Cells?

Answer 11

• B-cell receptors (BCR) on B cells
• T-cell receptors (TCR) on T cells

Question 12

What molecule(s) are present on T cells?

Answer 12

• CD4 molecules on Th cells
• CD8 molecules on Tc cells

Question 13

Describe:

BCR Structure

Answer 13

Comprised of 4 proteins
* 2x Light chain
* 2x Heavy chain

Question 14

What regions are both the TCRs and BCRs comprised of?

Answer 14

• Antigen-binding site
• Variable region (V)
• Constant region (C)
• Transmembrane region
• Cytoplasmic tail

Question 15

Where is the variable region in BCRs?

Answer 15

The light and heavy chain region where the antigen-binding site is

Question 16

Why are they called variable regions?

Answer 16

The amino acid sequences in these regions can vary

Question 17

What is the difference between B cell receptor and antibody?

Answer 17

They are the same molecule
* One is membrane-bound, the other is secreted
* One has a hydrophobic segment, the other has a hydrophilic segment

Question 18

Describe:

TCR Structure

Answer 18

2 proteins
* alpha chain
* beta chain

Question 19

Where is the variable region in TCRs?

Answer 19

The alpha and beta segments of the two proteins

Question 20

Do BCRs and antibodies have the same antigen specificity?

Answer 20

Yes, and they both bind antigens directly

Question 21

What is an antigen?

Answer 21

A molecule recognized by a BCR or TCR

Question 22

Are the secreted and membrane bound forms of BCR encoded by different genes?

Answer 22

No they are encoded by same genes

Question 23

What is an epitope?

Answer 23

The molecular surface that interacts directly with BCRs or TCRs

Question 24

What can larger antigens do to BCRs?

Answer 24

Can crosslink BCRs
* Large multivalent antigens will bind to multiple BCRs ands cluster them together
* This is because BCRs have multiple binding sites (2)

Question 25

What effect does crosslinking BCRs have on signals?

Answer 25

Multiple activated BCRs will strengthen the signal produced

Question 26

Describe:

Signal Transduction by BCRs

Answer 26

1. Lyn (tyrosine kinase) phosphorylates Ig alpha and Ig beta
2. BLNK protein brings another tyrosine kinase - Syk - onto Ig alpha and beta
3. Syk phosphorylation sends out additional signals

Question 27

How do TCRs differ from BCRs?

Answer 27

1. They don’t crosslink (only 1 binding site)
2. Only recognize peptides (8-24 amino acids) presented by MHC
3. Stabilized by CD4 or CD8

Question 28

Do individual B and T cells make receptors of multiple specificity?

Answer 28

No, each individual cell makes a receptor for one unique epitope
* Different cells may have a receptor for different epitopes, but each cell will only have one type

Question 29

What are BCRs and TCRs encoded by?

Answer 29

Recombined Genes

Question 30

What did Hozumi and Tonegawa discover in 1976?

Answer 30

Genes that encode antibodies and B cell receptors are located in various regions of the genome
* Consist of V, D, and J segments

Question 31

How does genetic recombination work for BCRs?

Answer 31

Segments of V, D, and J are brought together to encode antibodies and B cell receptors

Question 32

When does gene recombination/rearrangement occur?

Answer 32

During lymphocyte development (before cells encouter antigen)

Question 33

Why is rearrangement largely random?

Answer 33

To generate a diverse preexicsting repertoire of antigen specificities

Question 34

What are the 4 postulates of Clonal Selection Theory?

Answer 34

1. Each lymphocyte bears a single type of receptor with a unique specificity
2. Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation
3. The differentiated effector cells derived from an activated lymphocyte will bear recceptors of identical specificity to those of the parental cell from which that lymphocyte was derived
4. Lymphocytes bearing receptors specific for ubiquitous self molecules are deleted at an early stage in lymphoid cell development and are there fore absent from the repertoire of mature lymphocytes

Question 35

What acronym will I use to sum up the postulates of clonal selection theory?

Answer 35

UAMD
1. Unique specificity
2. Activation by antigen capable of binding
3. Multiplication of activated lymphocyte
4. Deletion of lymphocytes bearing receptors for ubiquitous self molecules