Vertebrate Immunity Lecture

Question 1

What are the 5 key requirements of the immune system?

Answer 1

1. Rapidly and efficiently eliminate dangers
2. Be able to recognise a diverse range of molecules
3. Be tightly controlled (up- and downregulated)
4. Be tolerant to own cells and tissues, and commensals
5. Memorise and transfer protection to progeny

Question 2

Name all types of phagocytic cells and their function.

Answer 2

Neutrophils, macrophages, and dendritic cells are all phagocytic cells. Of those, macrophages and dendritic cells function also as antigen presenting cells (APCs). Proteins that are eaten by APCs are broken down to small pieces (peptides), which are loaded on special receptors (MHCs) and transported to the cell surface. A peptide-MHC complex can be recognised by a T cell and that interaction can lead to an adaptive immune response.

Question 2

What does activation of a Toll-like receptor do?

Answer 2

TLR signalling activates the inflammatory response. A signalling cascade leads to NFkB inducing the expression of cytokines (TNF, IL-1, and IL-6), chemokines (CCL2, CXCL8, and others), endothelial adhesion molecules (E-selectin), and costimulatory molecules (CD80 and CD86).

Question 3

What is the structure of a Toll-like receptor?

Answer 3

Toll-like receptors have a ribbon-like extracellular domain that functions in pattern recognition. This exterior domain consists of leucine-rich repeats (LRRs). The cytoplasmic domain is called the toll/interleukin-1 receptor (TIR) domain, which function with the recruitment of a signalling complex.

Question 4

What are the hallmarks of inflammation?

Answer 4

Inflammation is characterised by capillary widening (resulting in increased blood flow), increased permeability (resulting in fluid release into tissues), attraction of leukocytes, and a systemic response (resulting in fever and proliferation of leukocytes). This all results in characteristic heat, redness, swelling, tenderness, and pain.

Question 5

Macrophages can polarise into two states. Explain these states.

Answer 5

Macrophages can differentiate into different phenotypes, of which the main extremes are M1 and M2, due to activation by certain compounds. The M1-macrophage phenotype has a pro-inflammatory, bactericidal, and phagocytic function. The M2-macrophage phenotype has an anti-inflammatory, matrix producing, pro-angiogenesis, and pro-wound healing function. Macrophage polarisation goes along with metabolic change. In the inflammatory M1-macrophage phenotype, due to two breaks in the TCA cycle, the production of antimicrobial nitric oxide is activated due to an excess of citrate, and due to an excess of succinate, IL-1B and IL-5 are produced. In the anti-inflammatory M2-macrophage phenotype, the TCA cycle is not broken at two points, resulting in an absence of nitric oxide, and IL-1B and IL-5 production.