Overview of the adaptive immune system

Question 1

There are four basic approaches to spot pathogens

Answer 1

1. It looks like a bad guy
   * Generic recognisable features e.g TLR – PAMPs
2. There’s trouble going on (their presence is associated with damage)

• Danger stimulation – co stimulation – CD28
• Damage associated molecular pattern molecules (DAMP) - recognises if pathogens are damaging
• Recognising danger as a route to tolerance

4. I’ve seen this one before and last time he was a bad guy

• Recognition
• Don’t get chickenpox as you have T-cells that stop you from getting disseminated

5. It’s not me – it shouldn’t be there

• Autoimmunity – self vs non-self
• Sees that it’s not itself

Question 2

How does the immune system set up a system to recognise things not yet seen?

What issues would this cause?

Answer 2

1. The massive array of possibilities approach.
2. Need balance between over and under-assiduous recognition

Don’t want self-recognition

The same pathogens often come back and attack again

• Opportunity to have effectors ready which are specific and potent

Some pathogens stick around

• Need controlling by effectors

Those effectors are primarily lymphocytes

Question 3

What does low CD4 count allow for?

Answer 3

Allows opportunistic infections to get through the immune defences to control it

Question 4

Examples of lymphocyte deficiency/defect syndromes

Answer 4

B cells

• Congenital agammaglobulinemia
• Common variable immunodeficiency (CVID)
• Novel biologics – Rituximab – treatment for lymphoma

T cells

• Severe combined immunodeficiency (SCID)
• DiGeorge syndrome – thymic failure
• Acquired – HIV /chemotherapy / Novel biologics

All create major, often life-threatening clinical problems

Question 5

How long does it take for adaptive immunity?

Answer 5

Several days, first 12-24 hours relying on innate immunity

Question 6

What are bridging cells?

Answer 6

Cells have memory properties.

preprogrammed for common cells.

between innate and adaptive immunity

• memory NK cells
• iNKT cells
• MAIT

Question 7

Lymphocytes have multidimensionality

Answer 7

Morphology

• White cell, small, large nucleus

Lineage

• T and B cells

Location

• Tissue resident memory cells
• Marginal zone B cells

Differentiation

• Naïve / memory (central, effector, stem cell memory)
• Immature / mature or differentiated / senescent

Function: what they do

• Helper / cytotoxic / regulatory / antibody-producing

Phenotype: what surface markers they express

• CD4, CD8, CD28 etc functional receptors

Specificity

• What target – what Ab produced or epitope recognised

Type of receptor

• Ig class for B cells

By what they produce

• TH1 (IL2, IFN-Y)
• TH2 (IL-4, IL-5, IL-6, IL-10)

Question 8

TCR need presenters

Answer 8

TCR detects a peptide sequence in association with MHC

• Pathogen peptides need to be processed and presented

All cells process their intracellular contents and present on MHC-1

• Recognised by CD8 t cells through TCR
• Crucial to defence against viruses

Specialised antigen present cells (APC) process and present peptides in MHC-II

• Binds to TCR on CD4 T cells

Question 9

Central and effector memory kinetics

Answer 9

TEM: Effector memory cells

• Short lived population
• Continually replenished
• Doubling time about 15 days

TCM: central memory cells

• Turnover at a significant rate
• Doubling time about 48 days

Treg: regulatory T cells

• Very dynamic
• Control the responses of other T cells

Question 10

B cell repertoire selection

Answer 10

Positive selection

Receptor editing

Negative selection

Transition to IgM+ IgD+ mature B cell

Antigen recognition leads to proliferation/ differentiation

Activated B cells turn into plasma cells