Infection 13 - Adaptive Immune Response (Part 2)

Question 1

Where are T+B lymphocytes produced + where do they mature?

Where do they accumulate?

Answer 1

• Produced in bone marrow, T-cells mature in thymus, B-cells in tissues following antigen contact
• Accumulate in key lymphoid tissues, e.g.: MALT, lymph nodes + spleen
• Activation causes lymphadenopathy (inguinal, cervical + axillary important)

Question 2

What is the antigen recognition receptor on T-lymphocytes composed of?
Which subtypes of T-lymphocytes recognise antigens presented by MHC class l and ll molecules?

Answer 2

• T-cell receptor (TCR) composed of a + b chains, a CD3 complex and accessory complex (CD4 or CD8)
• T-helper cells (CD4+) recognise peptides presented by MHC class ll molecules (extracellular pathogens)
• Cytotoxic T-cells (CD8+) recognise peptides presented by MHC class l molecules (intracellular pathogens)

Question 3

How does costimulation result in the activation of T-lymphocytes?

Answer 3

1) MHC class l or ll molecule binds to TCR
2) Activation of T-lymphocyte ALSO requires binding of B7 molecule on APC to CD28 on T-cell (hence co-stimulation)
3) In addition, APC’s secrete cytokines which tell the T-cell what the microbe is and what the response should be.

• 3 signals in total required for co-stimulation of T-cells

Question 4

What are the different T-helper responses in response to the following cytokines:

• IL-12
• IL-4

Answer 4

• IL-12 causes differentiation into CD8 T-cells, recruitment of macrophages and activation of B-cells for cell mediated immunity (against bacteria, viruses + fungi) - both intracellular and extracellular pathogens
• IL4 causes activation of B-cells, eosinophils + mast cells for humoral immunity (against parasites + worms)

Question 5

How to CD8+ cytotoxic T-cells kill infected cells?

How does the CD8+ cell know to only kill virus infected cells?

Answer 5

1) Release of perforin - to produce perforin pore in infected cell
2) Release of granzymes through pore into the cell triggering apoptosis.

• T-cell receptor on surface recognises the antigen being presented on the MHC molecule and only kills those presenting foreign virus

Question 6

How do the B-cells recognise the antigen to produce the correct antibody after T-cell activation?

Answer 6

• B-cell receptor (BCR) on B-cell has variable region specific to certain antigens.

Question 7

What are the 3 signals required for activation of B-lymphocytes?

Answer 7

1) BCR engagement - with specific antigen
2) TCR engagement - binding to MHC class l or ll
3) Cytokines - released to activate CD40 molecule on B-cells

Question 8

What is the outcome of B-lymphocyte activation?

Answer 8

1) Antibody production - IgM (T-helper independent), IgG, IgA + IgE (T-helper dependent/isotype switch)
2) Memory B-cells

Question 9

What are the effector functions of IgG, IgA, IgE + IgM

Answer 9

IgG = phagocytosis, complement activation, toxin/virus neutralisation
IgA = mucosal immunity
IgE = immunity against helminths + mast cell degranulation (allergies)
IgM = complement activation