B and T cell activation

Question 1

T cell circulation

Answer 1

Naive T cells recirculate between blood, lymphatics and secondary lymphoid tissues

Browses for APCs expressing MHC-peptide in lymph nodes

Question 2

Costimulatory signals

Answer 2

Required for optimal T cell activation

TCR signalling between TCR-CD3 on naive T cell and MHC on the APC

Co-stimulation signal via CD28

Cytokine signalling influences differentiation

Question 3

Co-stimulatory receptors

Answer 3

CD28 interacts with CD80/86 on APC for initial activation. ICOS interacts with ICOS-L on APC for effector and memory T cell differentiation (positive receptors)

CTLA-4 interacts with CD80/86 and down-regulates T cell response (negative receptor)

Question 4

Anergy

Answer 4

MHC recognition in absence of co-stimulation or MHC recognition with negative co-stimulation leads to anergy

Question 5

Superantigens

Answer 5

Simultaneously bind Vbeta region of TCR and alpha chain of MHCII
Polyclonal T-cell activation and dramatic cytokine release

Staphylococcus enterotoxin B
Endogenous superantigens can be encoded by retroviruses encoded in the genome

Question 6

IL-2

Answer 6

Activation of naive T cell increases secretion of IL-2 and its receptor IL-2R (CD25) leading to autocrine stimulation.
Proliferation
Memory T cells
Clonal effector T cells

Question 7

T helper subset differentiation

Answer 7

Released cytokines bind to receptors on CD4+ T cells and influence Th differentiation

Th1 subset important in cell-mediated immunity. Th2 subset important in humoral immunity.

Question 8

Memory T cells

Answer 8

Can be CD4+ or CD8+
Central memory T cells are found in the secondary lymphoid tissues and differentiate into Th subsets in response to infection.

Effector memory T cells are found in the periphery

Question 9

B cell circulation

Answer 9

Mature B cells in the follicles interact with an antigen and are clonally selected or recirculate through blood and lymphatics

Question 10

T-cell dependent activation

Answer 10

Antigen binding to BCR induces initial activation and proliferation.
Some antigen is presented on MHCII, which interacts with TCR on Th cell.
Interaction with Th cell allows differentiation and memory cell production

Question 11

Antigen presentation to B cells

Answer 11

Occurs in lymph nodes and spleen
Small antigen acquired from lymphatic circulation by follicular B cells

Larger antigens captured by subcapsular sinus macrophages and presented to B cells in follicles

Follicular dendritic cells act as antigen concentration sites

Question 12

B cell differentiation

Answer 12

Interactions between B and Th cells (CD40/40L, CD80/86) facilitate secretion of cytokines for full B cell activation.

B cells switch Ig isotypes via class switch recombination.
AID initiates DSBs in heavy chain genes by deaminating cytidine residues

Question 13

Germinal centres

Answer 13

Form 4-7 days after initiation of B cell activation

A few B cells migrate back to the primary follicles and proliferate rapidly.
Site of somatic hypermutation

Question 14

Somatic hypermutation

Answer 14

Occurs within germinal centres
Leads to generation of high-affinity antibodies
Affects mutational hotspots in the variable region genes of antibodies
Also mediated by AID

Question 15

Memory B cells

Answer 15

Produced in primary response from naive cells that don’t differentiate to plasma cells

Must be reactivated by antigen
Yield higher, faster and stronger response

Question 16

Long lived plasma cells

Answer 16

Reside in bone marrow and continually secrete antibodies

Question 17

T-independent B cells

Answer 17

TI-1 antigens interact with B cells via BCR and TLR (innate receptor)

TI-2 antigens fix complement fragment C3d and bind complement receptors

Question 18

Negative B cell regulation