Mediators of inflammation

Question 1

Self tolerance

Answer 1

A function of the adaptive immune system is to ensure that individuals do not respond to their own proteins

Question 2

Autoimmunity

Answer 2

breakdown in self tolerance
harmful immune reactions against self proteins

Question 3

Immune response

Answer 3

A collective and coordinated response to the introduction of foreign substances in an individual. Mediated by the immune system.

Question 4

Immune system

Answer 4

Molecules, cells and tissues that collectively function to provide protection against foreign organisms. Can be inadvertently activated by self-proteins

Question 5

T-lymphocyte

Answer 5

Cells that mediate cell mediated immune responses. T-cells mature in the thymus, circulate in blood and are recruited to peripheral sites of antigen exposure (from invading pathogen) or inflammation.

Question 6

B-lymphocyte

Answer 6

Only cell capable of producing antibodies. A central cellular component of the humoral immune response. Develop in the bone marrow.

Question 7

Phases of the immune response

Answer 7

1. naive T cells activated, undergo clonal expansion and differentiation into different effector populations
2. generates many T cells that can respond to the pathogen - either kill pathogen directly or recruit other immune components
3. effector T cells die by apoptosis when pathogen clears
4. never returns to 0 → small numbers of memory T cells present that respond rapidly upon re-exposure

Question 8

T lymphocytes

Answer 8

express receptors that recognise peptides derived from foreign proteins (T-cell receptor)

Question 9

T-cell subsets

Answer 9

• CD4+ T-cells (helper)
• CD8+ T-cells (cytotoxic)

Question 10

CD4 and CD8

Answer 10

co-receptors expressed on cell surface

Question 11

Functional subsets

Answer 11

are based on cytokine secretion

Question 12

Th1

Answer 12

T-cells that secrete IFN-gamma. Stimulate phagocyte mediated defence against foreign protein → play major role in many forms of autoimmune disease

Question 13

Th2

Answer 13

T-cells that secrete IL-4 and IL-5. Stimulate IgE / mast cell mediated immune responses

Question 14

Antigen processing

Answer 14

The intracellular enzymatic conversion of foreign protein into peptides and
loading onto proteins (MHC molecules) for presentation to T-cells

Question 15

Antigen presentation

Answer 15

The display of peptides bound to MHC molecules on the surface of an antigen presenting cell that permits recognition by T-cells

Question 16

Antigen presenting cell

Answer 16

A cell that processes protein antigens and expresses MHC molecules for presentation of the antigen to T-cells

Question 17

Antigen processing and presentation

Answer 17

APCs digest proteins to peptides

Peptide associates with MHC to form peptide-MHC complex

complex transported to cell surface

TCR responds

Question 18

APCs

Answer 18

B cells
Dendritic cells

Question 19

Exogenous antigen presentation

Answer 19

Proteolytic enzymes in endosomal vesicles breakdown (process) proteins into peptides

MHC class II molecules are synthesised, transported to the endosome

MHC class II associates with the peptide, which is subsequently transported to the cell surface

cell surface - only presents peptides to CD4+ cells

Question 20

Endogenous antigen presentation

Answer 20

Endogenous proteins are broken down by the proteosome complex in cytosol and associate with TAP

Peptides are transported from cytosol to the ER via the carrier protein TAP

Peptides bind to MHC class I in ER and transported to the cell surface - only presents peptides to CD8+ cells

Question 21

Properties of MHC molecules

Answer 21

Complex protein that consist of:

1. extracellular antigenic peptide binding groove - where TCR interacts to determine response
2. extracellular co-receptor binding region (surrounds peptide binding groove)
3. transmembrane domain - locks MHC onto surface of APC

Co-receptor binding domains bind either CD4 or CD8 receptor on T cell

Question 22

Peptide display molecules

Answer 22

-Peptides bind non-covalently to MHC

Peptides that bind to MHC contain amino acids that allow complimentary interactions

Interaction is saturable therefore should be able to develop antagonists to prevent MHC binding

(cf drug - receptor interaction)

MHC molecules show broad substrate specificity - present many different peptides on surface

Question 23

Co-stimulatory receptors

Answer 23

CD28

CTLA-4

Question 24

Tissue homing receptors

Answer 24

chemokine receptors

Question 25

Two signal hypothesis for initiation of T-cell activation

Answer 25

Signal 1 – peptide antigen cross linking MHC and the T-cell receptor Signal 2 – additional receptor signals provided by antigen presenting cells -in absence of second signal, T cell will not respond

Question 26

Co-stimulatory receptors on APCs

Answer 26

CD80 and CD86

Question 27

CD80

Answer 27

binds to CD28 on T-cells → ACTIVATION - this may be blocked in autoimmune disease

Question 28

CD86

Answer 28

binds to CTLA-4 on T-cells → NEGATIVE REGULATION

Question 29

Chemokines

Answer 29

small circulating signalling proteins Small (8-10KDa), soluble proteins released from inflamed tissue that stimulate movement of immune cells from blood to tissues

Question 30

Chemokine receptors

Answer 30

cell surface proteins, 16 different receptors have been identified interact with chemokines that transduce signals stimulating the migration of cells to specific tissues Blocking binding of chemokine to chemokine receptor may be beneficial

Question 31

Chemokine receptors are expressed on

Answer 31

Immune cells including T-cells, B-cells and macrophages