lecture 11 - innate immunity

Question 1

How do immune system cells communicate with each other?

Answer 1

Signalling with surface molecules e.g. CD molecules
or MHC molecules
Signalling through secreted molecules e.g. cytokines such as “interleukins” = IL-1 to IL-40

Question 2

How does the immune system work?

Answer 2

1. Barriers = skin, respiratory + digestive tracts
   - physical barrier e.g. epithelial cells
   - chemical barrier e.g. saliva, mucus
2. Innate Immune System = pre-existing before infection
   - fast (within minutes)
   - invariant receptors
   - broad specificity
   - no memory
   - eg macrophages and dendritic cells
3. Adaptive Immune System = adaptation to infection
   - slow (several days)
   - highly variant receptors
   - highly specific
   - generates memory
   - T cells and B cells

Question 3

Explain how the different levels of the immune function

Answer 3

When there is no/short disease, innate immunity kills the pathogen
If innate immunity does not kill the pathogen, adaptive immunity is activated
In an acute disease then clearance scenario adaptive immunity kills the pathogen
If adaptive immunity does not kill the pathogen this leads to chronic disease/death

Question 4

Describe immune cell development: haematopoiesis

Answer 4

Immune cells develop in primary lymphoid organs
The primary lymphoid organs are bone marrow and thymus
B cells produced in bone marrow and T cells in thymus
Adaptive Haematopoietic Stem Cell = HSC:
have lymphoid lineage and myeloid lineage
Myeloid lineage produces macrophages, dendritic cells, granulocytes
+RBC platelets

Question 5

Where do immune cells live?

Answer 5

1. Immune cells reside throughout the body in wait of
   invading pathogens e.g. in skin, intestine, lung
2. Immune cells migrate via lymph & blood to specialised secondary lymphoid organs e.g. spleen and lymph nodes
3. 2ry lymphoid organs have defined structures that
   promote adaptive immune responses

Question 6

What are the main stages in an immune response?

Answer 6

1. Recognition of pathogen (innate then adaptive)
2. Effector response (innate + adaptive)
3. Memory (adaptive only)
4. Immune turn off (= immune regulation)

Question 7

How do innate immune cells recognise pathogens?

Answer 7

Immune system must distinguish SELF vs. NON-SELF

• Different types of pathogens have evolutionarily conserved molecules we can recognise as NON-SELF = PAMPs
  i. e. PATHOGEN-ASSOCIATED MOLECULAR PATTERNS
• Innate immune cells have various PATTERN RECOGNITION RECEPTORS (= PRRs) to recognise PAMPs

Question 8

Describe the role of PRR and PAMP in innate immune cell recognition and activation

Answer 8

Large amounts of LPS on surface of G-ve bacteria
- Innate immune cells (e.g. macrophages + DCs) have
surface PRR e.g. Toll-like receptor 4 or TLR4
- LPS is a PAMP that binds to TLR4 on innate immune cells
- This results in ACTIVATION of innate immune cells

• TLR4 is mammalian homolog of Drosophila gene Toll
• Flies with mutation in toll die from massive fungal infection
• Innate immunity is primitive & evolutionarily conserved
• Innate immune cells express multiple PRR at the same time
• Each PRR recognises a different PAMP

Question 9

How are macrophages activated?

Answer 9

1. Macrophage kills bacteria
2. recruits other immune cells eg neutrophils- also phagocytic +cytokines and chemokines
   = INFLAMMATION

Question 10

How are dendritic cells activated?

Answer 10

Professional “Antigen Presenting Cell” = APC

1. Takes up pathogen proteins (phagocytosis)
2. Migrates to 2ry lymphoid organs e.g. lymph node
3. “Presents” fragments of pathogen proteins
4. These activate T cell response

Migrating DCs carry messages from sites of
infection to secondary lymphoid organs
This initiates ADAPTIVE immune response…