Lecture 32: Immunopathology - Autoimmunity

Question 1

What is type IV hypersensitivity mediated by and what do they secrete?

Answer 1

CD4+ T helper 1 cells which secrete IFNg

Question 2

What does IFNg activate?

Answer 2

tissue macrophages which secrete inflammatory mediators

Question 3

How long until type I hypersensitivity reactions are detectable after exposure to allergen?

Answer 3

5-10 minutes

Question 4

What are the three components of autoimmunity?

Answer 4

genetic susceptibility, environmental and loss of self-tolerance

Question 5

Why are circulating auto-reactive lymphocytes not always activated?

Answer 5

antigen is not available, absence of signal 2, auto-reactive B cells do not have auto-reactive CD4+ T cells

Question 6

What are dendritic cells activated by?

Answer 6

danger signals

Question 7

What do mature, naive B cells require to be activated and differentiate into antibody secreting cells?

Answer 7

two signals

cognate antigen and activation signal

Question 8

How do autoimmune diseases develop?

Answer 8

autoimmune responses do not always result in autoimmune diseases but all autoimmune diseases involve autoimmune responses

Question 9

What does autoimmunity result from?

Answer 9

a chronic (ongoing) autoimmune response with ongoing tissue damage

Question 10

How do macrophages respond to self antigens?

Answer 10

secrete nitric oxide, proteases and oxidative radicals

Question 11

How do CD4 and CD8 T cells respond to self antigens?

Answer 11

delayed type hypersensitivity responses, CTL killing of stromal cells and provision of B cell help

Question 12

What are delayed type hypersensitivity responses?

Answer 12

Th1 activation of macrophages, cytokine production, pro-inflammatory mediator release

Question 13

How do B cells respond to self antigens?

Answer 13

type II hypersensitivity (including ligand mediated reactions)
type III hypersensitivity (immune complex deposition)

Question 14

What are organ-specific autoimmune diseases?

Answer 14

diseases confined to particular organs or cell types and the antigens recognized are organ specific

Question 15

What are systemic autoimmune diseases?

Answer 15

diseases in which multiple tissues of the body are targeted and the antigens recognized are more ubiquitous

Question 16

What is the thyroid gland essential for?

Answer 16

regulating metabolism through the production of thyroid hormones

Question 17

Why does the pituitary gland secrete TSH?

Answer 17

acts on the thyroid to induce the release of thyroid hormones

Question 18

How do thyroid hormones act on the pituitary?

Answer 18

they shut down production of TSH, suppressing further thyroid hormone synthesis (feedback suppression)

Question 19

What is Graves disease?

Answer 19

autoantibodies bind to the TSH receptor on thyroid cells which stimulates the receptor, thus encouraging enhanced production of thyroid hormones -> hyperthyroidism

Question 20

What is Graves disease an example of?

Answer 20

type II hypersensitivity

Question 21

What is myasthenia gravis?

Answer 21

production of autoantibodies which inhibit acetylcholine receptor function (in the neuromuscular junction) -> no Na+ influx and no muscle contraction

Question 22

What are the three mechanisms by which myasthenia gravis inhibits transmission at the neuromuscular junction?

Answer 22

complement binding and activation at the NMJ, antigenic modulation and functional AChR block

Question 23

Which autoantigens are involved in systemic lupus erythematosus?

Answer 23

numerous autoantigens are involved and these are widely expressed

Question 24

What is observed in systemic lupus erythematosus?

Answer 24

B cell hyper-reactivity and presence of anti-DNA autoantibodies and immune complex deposition in kidney

Question 25

What causes systemic lupus erythematosus?

Answer 25

immune complex deposition on basement membranes of kidney -> activation of the complement cascade -> tissue injury caused by leukocyte activation and inflammation

Question 26

What is celiac disease?

Answer 26

type IV hypersensitivity which is not a true autoimmune disease

Question 27

What are people with celiac disease hypersensitive to?

Answer 27

wheat, barley and rye (gliadins, gliadin like molecules)

Question 28

How is the jejunum affected in celiac disease?

Answer 28

there is villous atrophy

Question 29

Why are people with celiac disease hypersensitive to gluten?

Answer 29

modified gluten peptides (gliadins) can bind with high affinity to HLA-DQ2 and HLA-DQ8 resulting in T cell activation
production of IL-15, activation of IELs

Question 30

What is gluten made up of?

Answer 30

is a complex mix of glutamine and proline rich poly- peptides (proline content provides stability in intestine)

Question 31

What is the role of tissue transglutaminase?

Answer 31

converts glutamine into glutamic acid (negative charge)

Question 32

What type of autoimmune disease is type 1 insulin dependent diabetes mellitus?

Answer 32

organ specific, T cell mediated (both CD4 and CD8)

Question 33

What occurs in type 1 insulin dependent diabetes mellitus?

Answer 33

autoimmune destruction of pancreatic beta-cells (insulin producing)

Question 34

What is type 1 insulin dependent diabetes mellitus characterised by?

Answer 34

infiltration of lymphocytes, weak autoantibody response, T cell reactivity to islet proteins
gradual loss of insulin secretion, and resultant insulin dependence

Question 35

In which people does type 1 insulin dependent diabetes mellitus occur more frequently?

Answer 35

in people with HLA DR3-DQ2 and DR4-DQ8

Question 36

What initiates the killing of beta cells in insulin-dependent diabetes?

Answer 36

an effector T cell recognises peptides from a beta cell-specific protein and kills the beta cell

Question 37

What is multiple sclerosis?

Answer 37

polygenic degenerative disorder of the CNS that results in episodes of paralysis during formative disease, with chronic paralysis in the latter stages

Question 38

What is MS caused by?

Answer 38

CD4 T cells specific for myelin antigens promote an inflammatory response and degrade the myelin sheaths covering nerve axons

Question 39

What initiates inflammation which induces recognition of self antigen?

Answer 39

infection with microorganism

exposure of self antigen due to dying cells