Autoimmunity - delayed-type hypersensitivity (Block 6)

Question 1

Mechanisms of immunological disease are…

Answer 1

… the same as all immune responses

Question 2

Delayed-type hypersensitivity disease examples

Answer 2

Insulin-dependent diabetes mellitus
Rheumatoid arthritis
Multiple sclerosis
Peripheral neuritis

Question 3

T cells thought to bring about RA are specific to

Answer 3

Collagen

Question 4

T cells thought to bring about MS are specific to

Answer 4

Myelin basic protein

Question 5

Specificity of T cells thought to bring about peripheral neuritis

Answer 5

Peripheral nerve myelin

Question 6

T-cells that bring about diabetes are thought to be specific to

Answer 6

Insulin

Question 7

What type of cells are involved in delayed-type hypersensitivity?

Answer 7

CD4+ T cells

Question 8

What happens when CD4+ T cell is activated?

Answer 8

Secretes cytokines, particularly INF-Gamma

Question 9

What does INF-Gamma do?

Answer 9

Activate phagocytic cells like macrophages and neutrophils

Question 10

What happens when phagocytes are activated?

Answer 10

Release TNF-alpha, produces ROS and NO in high levels
Cause inflammation

Question 11

Insulin-dependent diabetes mellitus

Answer 11

Multi-system metabolic disease that results in impaired insulin production and therefore function

Question 12

Chronic symptoms of diabetes

Answer 12

Atherosclerosis of arteries
Necrosis of organs
Damage to retina. Renal glomeruli, and peripheral nerves

Question 13

Commonality of insulin-dependent diabetes

Answer 13

Affects 0.2% of population
Peak age onset is 11/12 years

Question 14

Insulin-dependent diabetes - susceptibility factors

Answer 14

95% of susceptible individuals express HLA-DR3 or DR4, in comparison to 40% of healthy controls
Viral infection

Question 15

Multiple Sclerosis

Answer 15

Disease of the CNS
Inflammation and demyelination of nerves
Characterised by weakness, paralysis, and ocular symptoms

Question 16

Mechanism of MS

Answer 16

CD4+ T cells, which secrete IFN-gamma, react against antigens
Activation of macrophages around nerves in brain and spinal cord -> myelin destruction

Question 17

Commonality of MS

Answer 17

Most common in young adults

Question 18

MS progression

Answer 18

Progressive disorder; health declines with time
Myelin activated T-cell migrate into CNS, encounter further myelin proteins and secrete cytokines, recruit macrophages and lead to myelin destruction -> cycle

Question 19

MS susceptibility factors

Answer 19

HLA-DR2
Viral infection

Question 20

Rheumatoid arthritis

Answer 20

Disease of the joints
1/3 of patients will become severely disabled within 20 years
Inflammation of synovial associated with destruction of joint cartilage and bone

Question 21

Mechanism of RA

Answer 21

Activated T cells & macrophages secrete cytokines that activate resident synovial cells to produce proelytic enzymes that mediate tissue damage

Question 22

Antigen of RA

Answer 22

Nature of antigen is not known; thought to be collagen

Question 23

RA susceptibility factors

Answer 23

HLA-DR1 & 4
Viral infection

Question 24

Cell-mediated autoimmune disease - CD8+

Answer 24

CD8+ cytotoxic T-cells kill virally infected cells
Virus may injure infected cells; THUS destruction of the host cell and virus is usually advantageous to the host
HOWEVER, certain viruses have no adverse effects
T-cells cannot discriminate between latent and destructive viruses and therefore destroy ALL infected cells

Question 25

Examples of autoimmune cytolysis are

Answer 25

Viral hepatitis Viral myocarditis Nb: these are rare