Overview of the Adaptive Immune System

Question 1

Why do we have an adaptive immune system?

Answer 1

Protection from and defence against pathogens
- Also role in malignancy surveillance
- Also linked to damage healing and repair
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

Question 2

What are the four basic approaches to spot a pathogen?

Answer 2

1. It looks like a bad guy
   
   • Generic recognisable features – eg TLR – PAMP’s
     2. There’s trouble going on (Their presence is associated with damage)
   • The Danger Hypothesis – co-stimulation – CD28
   • Damage-associated molecular pattern molecules (DAMP)
     3. I’ve seen this one before .. and last time … he was a bad guy
     4. It’s not me – It shouldn’t be there
   • Autoimmunity … self-versus non-self

Question 3

What are some examples of lymphocyte deficiency/defect syndromes?

Answer 3

Primary / Secondary
B cells
- Congenital agammaglobulinaemia- not making enough antibodies
- Common variable immunodeficiency (CVID)
- Novel biologics – Rituximab takes out B cells
T cells
- Severe Combined Immunodeficiency (SCID), mostly in children
- DiGeorge syndrome -thymic failure
- Acquired – HIV / Chemotherapy / Novel biologics
All create major, often life-threatening clinical problems

Question 4

What are the key points of adaptive immunity?

Answer 4

Two key features:
	- Specificity
	- Memory
The pivotal role of clonal selection
	- One clone – one specificity
	- Progeny of that clone can be expanded and retained

Question 5

How does the one cell, one specificity rule apply to B and T cells?

Answer 5

Basic tenet – one cell / one specificity
For B cells – one cell, one Ig
- Defined by their antibody
- May class switch / undergo affinity maturation
- but always the same basic Ig
For T cells – one cell, one T cell receptor – TCR
- Selection and expansion of that clone ± differentiation
- Retention in “memory” of clonal progeny
This causes continued protection
- Continued production of antibody (B cells / Plasma cells)
- More rapid specific secondary responses (B and T cells)

Question 6

How do T cells recognise peptides?

Answer 6

It detects a peptide sequence in association with MHC

- Pathogen peptides need to be processed and presented
- Needs an antigen-presenting cell

All cells process their intracellular contents and present on MHC-I
- Recognised by CD8 T cells through their TCR
- Crucial to defence against viruses
- Some viruses will try to supress MHC but some immune cells kill cells without MHC
Specialised antigen-presenting cells (APC) process and present peptides in MHC-II
- binds to TCR on CD4 T cells

Question 7

What are the different memory T cell types?

Answer 7

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
	- Also very dynamic
	- Control the responses of other T cells
Tissue-resident memory cells
	- ?Long lived

Question 8

What is the difference btween TEM and TCM?

Answer 8

Central Memory 
TCM
	- CCR7+ CD62L+
	- Enter LN and recirculate
Effector Memory 
TEM
	- CCR7- CD62L-
	- Migrate into tissues
	- Rapid effector activity
	· Cytolytic, Cytokines (IFg/IL4/IL-5)

Question 9

How does anatomy matter in terms of the immune system?

Answer 9

The anatomy of lymphocytes
Organised mainly into Lymph Nodes
- Architecture optimised to facilitate cellular interaction
Key role of Spleen in antibody generation
- Splenectomy increases the risk of infection
- Especially pneumococcal infection – recommend vaccination