Lecture 21: Cell mediated immunity and lymphocyte ontogeny

Question 1

Reminder about MHC classes and t cell interactions

Answer 1

CD4 TH cell with MHC class 2 on APC
CD8 T killer with MHC1 on virus effected

Question 2

CD8 T cell clonal activation

Answer 2

MHC class 1 binds to particular TCR,helped by cytokines and co stimulators
Proliferates and differentiates into memory cells and T killer cells

Question 3

Cytotoxic T cell killing mechanisms

Answer 3

1) Perforin + enzymes for polymerisation
2) Hydrolytic enzymes
3) Cytokines e.g TNF-a, TNF-B, INF-y that induce apoptosis

Question 4

B cell ontogeny

-In bone marrow, uncommitted ___ cell
-___ B cell with cytoplasmic _ chains
-Immature B cell with ____
Mature B cell with ____ and ____

Answer 4

In bone marrow, uncommitted stem cell
-Pre B cell with cytoplasmic u chains
-Immature B cell with sIgM
Mature B cell with sIgM and sIgD

Genes have been rearranged

Question 5

Genetic rearrangements and B cell ontogeny
Two regions on DNA coding for light ad heavy chains

-Heavy chain region: _, _ and _ exons that code for _____ region of heavy chain. One exon from each is selected and combined with constant part to heavy chain(u,d,e,a etc)
Transcription, translation and splicing produce ____ _____ ___

INDEPENDENT of _____

Light chains: _ and _ exons with one constant region. (kappa and lambda). ____ rearrangement, of a V and a J- variable region of light chain.

Combines with heavy chain, to make surface IgM

Answer 5

Two regions on DNA coding for light ad heavy chains

-Heavy chain region: V,D and J exons that code for variable region of heavy chain. One exon from each is selected and combined with constant part to heavy chain(u,d,e,a etc)
Transcription, translation and splicing produce cytoplasmic u chains

INDEPENDENT of ANTIGENS

Light chains: V and J exons with one constant region. (kappa ad lambda). random rearrangement, of a V and a J- variable region of light chain.

Combines with heavy chain, to make surface IgM

Question 6

Due to random nature and extensive number of epitope regions we can make, how do we ensure none can harm our own antigens

Answer 6

While immature B cell, if it will self react, are deleted before mature and migrate to secondary lymphoid organs

Known as central tolerance

Question 7

How do antibodies switch classes? I.e have different heavy chains but same variable regions

Answer 7

Initially IgM is made due to u exon being closest. These m chains can be removed from DNA to have variable region associated with y constant chain

Question 8

Important B cell ontogeny points

Development in ____ ____
Multiple V,D and J exons recombine- _ region
Recombination _____ of antigen
Variable region diversity due to this
B cells committed to one V_ and one V_
Single constant region exons for one ____
Negative selection to remove strong self _____
Class switching retains _ region, changes _ region

Answer 8

Development in bone marrow
Multiple V,D and J exons recombine- V region
Recombination independent of antigen
Variable region diversity due to this
B cells committed to one VH and one VL
Singe constant region exons for one class
Negative selection to remove strong self reactivity
Class switching retains V region, changes C region

Question 9

T cell ontongeny

• Uncommitted _____ in the ____
• ___ genes rearrange (TCRaB): a and B regions. V, D and J ____ on B gene line. V region
• Recombination _____ of antigen
• Now express both ___ and ____
• _____ selection occurs: If these T cells do not recognise HLA 1 or 2, are killed
• Down regulate either CD4 or CD8 that they do not need.
• ____ selection occurs: Anti self HLA + self peptide lineages are killed. (prevent harming us)
• HLA + foreign peptide cells remain, CD3 added to have Th cell and Tk cell. Exported to secondary lymphoid organs

Answer 9

• Uncommitted thymocyte in the cortex
• TCR genes rearrange (TCRaB): a and B regions. V, D and J combine on B gene line. V and J on a gene line.
• Recombination independent of antigen
• Now express both CD4 and CD8
• Positive selection occurs: If these T cells do not recognise HLA 1 or 2, are killed
• Down regulate either CD4 or CD8 that they do not need.
• Negative selection occurs: Anti self HLA + self peptide lineages are killed. (prevent harming us)
• HLA + foreign peptide cells remain, CD3 added to have Th cell and Tk cell. Exported to secondary lymphoid organs

Question 10

Note on importance of HLA

Answer 10

HLA will determine the T cell repertoire due to positive selection