(Section B: Immunology) Lecture 13: T-Cell Immunity I Flashcards
What theory did Paul Erhlich come up with?
Side Chain Theory
What lymphatic organ did Jacques Miller research in 1960?
Thymus
What did the removal of the thymus have on mice?
- Could no longer make antibodies in response to immunization
- Could longer immunologically reject a skin graft
What were cells produced by the thymus called?
T Cells
* “T” for “thymus”
What lymphatic organ did Max Cooper research in 1965?
Bursa of Fabricius in birds
What effects did the removal of the Bursa of Fabricius have on chickens?
- Could not produce antibodies
- Could still reject skin grafts
What cells did the Bursa of Fabricius produce?
B Cells
* “B” for “bursa”
Where are B cells produced in mammals?
Bone marrow (“B” for “bone marrow”)
* Area rich in cytokines, growth factors, HSC, endothelial cells etc
How do B Cells and T Cells look?
They look similar to each other
What types of T and B Cells are there?
- T helper cells (Th)
- T cytotoxic cells (Tc)
- B cells
What are the cell receptors for T and B Cells?
- B-cell receptors (BCR) on B cells
- T-cell receptors (TCR) on T cells
What molecule(s) are present on T cells?
- CD4 molecules on Th cells
- CD8 molecules on Tc cells
Describe:
BCR Structure
Comprised of 4 proteins
* 2x Light chain
* 2x Heavy chain
What regions are both the TCRs and BCRs comprised of?
- Antigen-binding site
- Variable region (V)
- Constant region (C)
- Transmembrane region
- Cytoplasmic tail
Where is the variable region in BCRs?
The light and heavy chain region where the antigen-binding site is
Why are they called variable regions?
The amino acid sequences in these regions can vary
What is the difference between B cell receptor and antibody?
They are the same molecule
* One is membrane-bound, the other is secreted
* One has a hydrophobic segment, the other has a hydrophilic segment
Describe:
TCR Structure
2 proteins
* alpha chain
* beta chain
Where is the variable region in TCRs?
The alpha and beta segments of the two proteins
Do BCRs and antibodies have the same antigen specificity?
Yes, and they both bind antigens directly
What is an antigen?
A molecule recognized by a BCR or TCR
Are the secreted and membrane bound forms of BCR encoded by different genes?
No they are encoded by same genes
What is an epitope?
The molecular surface that interacts directly with BCRs or TCRs
What can larger antigens do to BCRs?
Can crosslink BCRs
* Large multivalent antigens will bind to multiple BCRs ands cluster them together
* This is because BCRs have multiple binding sites (2)
What effect does crosslinking BCRs have on signals?
Multiple activated BCRs will strengthen the signal produced
Describe:
Signal Transduction by BCRs
- Lyn (tyrosine kinase) phosphorylates Ig alpha and Ig beta
- BLNK protein brings another tyrosine kinase - Syk - onto Ig alpha and beta
- Syk phosphorylation sends out additional signals
How do TCRs differ from BCRs?
- They don’t crosslink (only 1 binding site)
- Only recognize peptides (8-24 amino acids) presented by MHC
- Stabilized by CD4 or CD8
Do individual B and T cells make receptors of multiple specificity?
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
What are BCRs and TCRs encoded by?
Recombined Genes
What did Hozumi and Tonegawa discover in 1976?
Genes that encode antibodies and B cell receptors are located in various regions of the genome
* Consist of V, D, and J segments
How does genetic recombination work for BCRs?
Segments of V, D, and J are brought together to encode antibodies and B cell receptors
When does gene recombination/rearrangement occur?
During lymphocyte development (before cells encouter antigen)
Why is rearrangement largely random?
To generate a diverse preexicsting repertoire of antigen specificities
What are the 4 postulates of Clonal Selection Theory?
- Each lymphocyte bears a single type of receptor with a unique specificity
- Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation
- 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
- 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
What acronym will I use to sum up the postulates of clonal selection theory?
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
