Overview of the adaptive immune system

Question 1

What is the immune/lymphocyte repertoire?

Answer 1

Lymphocyte repertoire creates a range of receptors able to recognise foreign antigens from a diversity of recognition receptors (TCR) and antibodies as a result of gene recombination.

Question 2

How does breast feeding help babies?

Answer 2

Breast feeding allows newborns to acquire antibodies and immune cells from mother - whilst their own adaptive immune system is developing.

Question 3

Lymphocyte morphology?

Answer 3

In resting state, B and T cells appear similar, so characterised by receptors expressed.

Plasma cells have large rough ER - in order to generate antibodies…
High nucleus:cytoplasm ratio, but are quite small and rounded.

Not very granular as do not phagocytose

Question 4

What are APCs?

Answer 4

Specialised cells which capture microbes + foreign antigens, in order to present them to lymphocytes in conjunction with other costimulatory signals.

Dendritic cells are main APCs in epithelia and most organs.
but include macrophages, neutrophils.

APC takes up antigen, processes it, and carries to T cells in Lymph nodes.
= T cells require a processed antigen

Question 5

What is the importance of lymphoid organs?

Answer 5

All lymphocytes originate in bone marrow and are derived from haematopoeitc stem cells.

B cells mature in bone marrow whilst T cells migrate to the thymus to mature and undergo selection = primary lymphoid organs..

Mature/ naive lymphocytes leave primary lymphoid organs (thymus/bone marrow) and enter circulation to reach lymph nodes, which are the secondary lymphoid organs.

Effector cells then migrate into tissue and return through lymphatic system!

Antigens entering through epithelia are carried in lymphatic system to lymph nodes…
Blood bourne antigens enter the spleen..

Question 6

How are B and T cells arranged in the lymph node?

Answer 6

B cells take up residence in B cell follicles, whilst T cells tend to congregate in the centre of T cells.

Antigen-laden dendritic cells (APCs) or soluble antigen arrives via afferent lymphatic vessels or via blood vessels.

And cause activation of T cell - which can re-enter circulation OR.
Co-localise with B cells to trigger B cell differnetiation and antibody production.

Question 7

What are the effector responses to antigen?

Answer 7

T cells = cell mediated toxicity = Tc cells.
Activation of macrophages for phagocytosis + recruitment of neutrophils.
Cytokine release

B cells = antibody production to enhance phagocytosis.

Question 8

What are the different cytokines released by T cells.

Answer 8

IFN-y, TGF-b, lymphotoxin (TNFb) and IL-2,4,5,13…
Most activate other cells + stimulate antibody production.

T regs produce Il-10 and TGB-b as inhibitory..

Macrophages are main pro-inflammatory cytokine producers in the innate system whilst T cells are for the adaptive system.

Question 9

How does the adaptive system return to homeostasis?

Answer 9

One antigen has been eliminated, homeostasis must occur.

Apoptosis of excess cells, survival of memory T and B cells.
= primed to response again upon antigen re-exposure

During infection, lymphocytes will undergo clonal expansion. BUT
if antigen persists, prolonged activation of T and B cells can lead to autoimmunity and chronic inflammation…

Question 10

How are B cells activated?

Answer 10

B cells are activated by engagement of surface antibodies (IgM and IgD receptors) and costimulatory signals from T cells.
Without costimulatory signal = anergy/tolerance.

Antigenic challenge of B cells in lymph nodes results in antigen processing and presentation to Th cells via MHC class II.

B cell receptors and antibody associated with two invariant chains (Igalpha and Igbeta) which transduce signal intracellularly.=, Syk kinase.

B cell receptor/antigen complexes are internalised and antigen fragments are presented on Class II MHC.

With signals enhanced by engagement of complement coreceptor - leading to activation of PI3-Kinase.

Question 11

How can B cell activation be inhibited?

Answer 11

After sufficient antibody production, IgG antibody can bind to Fc-coreceptor to downregulate response and reverse actions of PI3-kinase.

Question 12

How do T cells help with B cell activation?

Answer 12

T cells provide costimulatory signals to enhance B cell activation.

B cells present antigenic fragment to T cells, which recognise via T cell receptor.

This leads to upregulation of CD40L. and IL-4.

Costimulation!

CD40L expressed on T cell engages with B cell surface CD40 receptor = stimulating antibody production and B cell clonal expansion of
AND
IL-4 expression + secretion activates B cell IL-4 receptor = further stimulating antibody production.

Question 13

What antigens can activate B cells independently to T cells?

Answer 13

These antigens do not trigger class switching or memory…
Allergens - repeated units of epitope are sufficient for B cell activation.

Question 14

What antibodies are expressed on B cell surface?

Answer 14

IgD and IgM receptors.

Question 15

What is Class switching?

Question 16

What is somatic hypermutation?

Question 19

What is roles of Th1 and Th2 cells?

Role of Th cells?

Answer 19

The main role of the TH1 cells is to stimulate cell-mediated responses (those involving cytotoxic T cells and macrophages), while TH2 cells primarily assist in stimulating B cells to make antibodies.

Helper T cells do not directly kill infected cells, as cytotoxic T cells do. Instead they help activate cytotoxic T cells and macrophages to attack infected cells, or they stimulate B cells to secrete antibodies. Helper T cells become activated by interacting with antigen-presenting cells, such as macrophages. Antigen-presenting cells ingest a microbe, partially degrade it, and export fragments of the microbe—i.e., antigens—to the cell surface, where they are presented in association with class II MHC molecules.

B7-CD28 interaction between APC and Th cells..

If only the first signal is received, the T cell may be rendered anergic—that is, unable to respond to antigen.

Question 21

What does IL-2 do?

Answer 21

IL-2 released by Th1 cells:

Enables cytotoxic or regulatory T cells that recognize the same antigen to become activated and to multiply.