T and B cells, cytokines and dendritic cells

Question 1

How do cells of the immune system communicate between themselves, and with other non-immune cells?

Answer 1

1. Cell-cell contact (signalling through receptor -ligand interactions between membranes of different cells, (eg MHC and TcR)
2. Secretion of soluble factors that initiate responses and signals by binding to specific receptors (e.g. cytokines)

Question 2

Define cytokines.

Answer 2

Small polypeptides, around 25,000 Mr released by cells in response to an activating stimulus. Can have autocrine, paracrine and endocrine (latter limited by ability to enter circulation and half-life) actions.

Question 3

Define chemokines.

Answer 3

A class of cytokine that has chemoattractant properties, ie induces cells to migrate towards the source.

Question 4

Define interleukins.

Answer 4

Cytokines secreted by leucocytes

Question 5

Identify the main groups if chemokines. Why were these groups get named the way they did ?

Answer 5

1. CC (which bind to receptors CCR1 to 9)
2. CXC (which bind to CXCR1 to 5)

Named due to spacing of cysteine residues close to amino terminus (two N-terminal cysteines of CXC chemokines separated by one amino acid VS two adjacent cysteines near their amino terminus).

Question 6

Describe the main features of IL-8, including source, receptors, target cells, major effects, and type of cytokine.

Answer 6

• CXC Chemokine
• Source: Monocytes, macrophages, fibroblasts, keratinocytes, endothelial cells
• Receptors: CXCR1 and CXCR2
• Target cells: Neutrophils and naive T cells
• Major effects: Mobilises, activates and degranulates neutrophils + Angiogenesis + induces chemotaxis in target cells, causing them to migrate toward the site of infection and induces phagocytosis once they have arrived

Question 7

Describe the function of Interleukin 2. How is it secreted ?

Answer 7

Activates and grows T cells (growth factor for other T cells)
Secreted by T cells

Question 8

Describe the function of Interleukin 4.

Answer 8

Activates and grows B cells + switches them to produce IgE (important in allergy)

Question 9

Describe the function of Interferon gamma.

Answer 9

Activates strong cell mediated responses (e.g. Cytotoxic T lymphocytes) + Causes upregulation of MHC class 1 and 2.

Question 10

Describe the function of TNF-alpha. How is it secreted ?

Answer 10

Pro-inflammatory (activates vascular endothelium and increases vascular permeability)
Secreted by T cells

Question 11

What treatment is there to dampen down pro-inflammatory response of TNF (e.g. in rhumatoid arthritis) ?

Answer 11

Inflixamab

Question 12

Do cells produce one type of cytokine only or more than one ?

Answer 12

A cell will tend to produce different cytokines with different effects on cells

Question 13

How do neutrophils access infection sites ?

Answer 13

Neutrophils access infection sites by diapedesis

Question 14

What is a problem associated with TNF alpha release ?

Answer 14

Its release normally triggers local protection (by allowing lymphocytes to travel thanks to decreased vascular permability, but can induce systemic shock –> if overproduction of TNF-alpha)
Notably including systemic oedema, decreased blood volume, hypoproteinemia, neutropenia followed by neutrophillia, collapse of vessels. May result in death

Question 15

Describe the process through which Interleukin 2 induces proliferation of T cells.

Answer 15

1. Naive T cells express the low affinity IL-2 receptor
2. Activated T-cells express the high affinity IL-2 receptor and secrete IL-2
3. Binding of IL-2 to high affinity receptor sends a signal to the T cell
4. The signal sent from IL-2 receptor induces T cell proliferation

Question 16

Identify the types of CD4 T cells, distinguishing between the two.

Answer 16

TH1 CELL (cell mediated immunity):

• Produce cytokines which result in:
• Macrophage activation
• B cell activation
• Production of opsonising antibodies

TH2 CELL (antibody responses:

• Produce cytokines which result in:
• General activation of B cells to make antibodies

Question 17

Describe the activation of B cells by TH2 cells.

Answer 17

1. Antigen recognition induces expression of CD40 ligand and cytokines by the TH2 cell, which activates the B cell
2. B cell proliferation and differentiation to antibody-secreting plasma cells.

Question 18

Define dendritic cells and decribe their function.

Answer 18

• Professional antigen presenting cells that sit at the interface between the innate and adaptive immune response.
• Highly phagocytic, sampling their external environment. Upon stimulation, cease phagocytosis and migrate to lymph nodes.
• In lymph nodes (clusters of B cells and T cells around the dendritic cells), activate T cells and influence B cells, to initiate immune response

Question 19

Where are dendritic cells found ?

Answer 19

In most surface epithelia

Question 20

Provide some of the other names of dendritic cells.

Answer 20

Langerhans cells in skin, interdigitating cells, follicular dendritic cells (FDC), veiled cells (when travelling in circulation)

Question 21

How long do follicular dendritic cells hold onto antigens for ?

Answer 21

• FDC can hold on to antigen for extended periods of time, possibly many days (good at immunological memory)
• The antigen is in the form of antigen-antibody-complement complexes, bound to Fc and complement receptors on the FDC surface
• The complexes do not appear to undergo internalisation

Question 22

True or False: Plasma cells are activated B lymphocytes

Answer 22

True

Question 23

How do dendritic cells link to innate immunity ?

Answer 23

• Express Pattern Recognition Receptors (PRR, recognise patterns that are in pathogens and not in our cells ), members of the Toll-like receptor Family (TLR)
• Several PMN (polymorphonuclear leukocytes) cells also express PRR

Question 24

Where in/on the dendritic cells are Toll-like receptors located ?

Answer 24

These sit on dendritic cell surface.

Question 25

List the ligand of the first 11 Toll-Like Receptors on Dendritic Cells.

Answer 25

• TLR1 and 2: lipopeptides
• TLR3: dsRNA
• TLR4: Lipopolysaccharide, heat shock proteins
• TLR5: flagellin
• TLR6: lipoproteins
• TLR7: ?
• TLR8: ssRNA
• TLR9: CpG(cytosine-phosphate-guanosine, bacterial DNA
• TLR10: ?
• TLR11: bacterial components.