Autoimmunity

Question 1

when does autoimmunity occur?

Answer 1

when the immune systems self-tolerant mechanisms breakdown

Question 2

what develops in autoimmunity?

Answer 2

autoreactive antibodies and autoreactive T cells develop

Question 3

what do autoreactive antibodies and autoreactive T cells recognise?

Answer 3

self antigens i.e normal components of the body

Question 4

Describe the spectrum of autoimmunity.

Answer 4

Can be organ-specific or involve many organs

Question 5

what causes enlarged thyroid in Hashimotos thyroiditis (organ specific)?

Answer 5

antibodies are directed against thyroglobulin

Question 6

Describe the changes in Hashimoto’s thyroiditis.

Answer 6

-Normal thyroid gland- Acinar epithelial cells (aec)
secrete thyroglobulin into
colloid spaces (cs)
-Hasimotos thyroid gland-Normal architecture virtually
destroyed, replaced by invading cells (ic) - lymphocytes, macrophages
& plasma cells

Question 7

what do autoantibodies bind to in autoimmunity?

Answer 7

self antigens

Question 8

what does antibodies in serum of hashimotos disease patient bind to?

Answer 8

residual
thyroglobulin in colloid
and acinar epithelial cells

Question 9

what does antibodies in serum of SLE patient bind to?

Answer 9

nuclei (N) of acinar epithelial cells

Question 10

Name organ-specific autoimmune disease.

Answer 10

• Thyroid i.e hashimotos, thyroiditis
• Stomach-pernicious anaemia
• Adrenal- Addison’s disease
• Pancreas-insulin dependent diabetes mellitus

Question 11

Name non organ-specific disease.

Answer 11

• Muscle-dermatomyositis
• Kidney-SLE
• Skin-scleroderma
• Joints-rheumatoid arthritis

Question 12

What are important facts of autoimmune diseases?

Answer 12

1. An individual may have more than one autoimmune disease e.g. Rheumatoid Arthritis often associated with SLE
2. Autoimmune diseases can occur in families, Certain HLA haplotypes predispose to autoimmunity

Question 13

how prevalent is autoimmune disease?

Answer 13

3.5% population have autoimmune disease

Question 14

what gender is more likely to develop autoimmune disease?

Answer 14

Overall, women are 2.7x more likely than men to develop autoimmune disease
-Female:male ratio can be even higher eg 10:1 in SLE

Question 15

What can human autoantibodies be directly?

Answer 15

pathogenic i.e graves disease

Question 16

Describe the cause of graves disease.

Answer 16

• AutoAb produced to receptor for Thyroid Stimulating Hormone (TSH)
• Act on receptor
• stimulate thyroid cell
• overproduction of thyroid hormones

Question 17

what causes pernicious anaemia?

Answer 17

AutoAb directed against Intrinsic Factor

Question 18

Describe the cause of pernicious anaemia.

Answer 18

Normally dietary vitamin B12 is absorbed as a complex with intrinsic factor (IF)
In pernicious anaemia autoantibodies directed against IF are produced
Binding of autoantibody to IF prevents interaction with Vit B12
As a result, Vit B12 is not absorbed

Question 19

Describe immunopathological damage (specific organ).

Answer 19

• When autoAg is localised to a particular organ
• type II hypersensitivity and cell-mediated reactions
• damage due to complement activation and phagocyte degranulation

Question 20

Describe immunopathological damage (non specific organ).

Answer 20

• immune complexes appear to be pathogenic in systemic autoimmunity e.g. in SLE deposits of IC in the kidney
• type III hypersensitivity reactions
• acute tissues damage

Question 21

Describe the pathology of rheumatoid arthritis.

Answer 21

-Inflammatory infiltrate found in synovial membrane
-Erosion of synovial cartilage and bone
-IC and neutrophils present in joint space
-IC can arise through self association of rheumatoid
factors = IgG molecules with unusual oligosaccharides

Question 22

Name 3 examples of autoimmune diseases affecting head and neck (affect thyroid).

Answer 22

• Hashimotos thyroiditis
• autoimune colloid goiter
• graves disease

Question 23

Describe the spectrum of autoimmune thyroid disease.

Answer 23

• thryoid destruction
• cell division :stimulation or inhibition
• thyroid hormone synthesis :stimulation or inhibition

Question 24

What is sjogren syndrome?

Answer 24

Chronic inflammatory autoimmune disorder

Question 25

how can sjogren syndrome occur?

Answer 25

Can occur in isolation or with SLE, RA or other rheumatic autoimmune disorders

Question 26

what are the majority of patients with sjogren syndrome?

Answer 26

• Majority of patients are women :
• symptoms develop in 4th-5th decade
• actual onset probably in 1st-2nd decade

Question 27

How much of the population does sjogren syndrome affect?

Answer 27

1-2% of population

Question 28

how issjogren syndrome characterised?

Answer 28

-Characterised by a lymphocytic infiltrate in
salivary and lacrimal glands :slow destruction and replacement of glandular tissue with fibrotic tissue

• Lack of salvia and tear secretion : dental caries, oral candida
• condiiton confirmed (60% of patients) by presence in serum of autoantibodies

Question 29

What are side effects of sjogrens syndrome ?

Answer 29

• dry lips
• dry and lobulated tongue
• caries

Question 30

Describe some ways treatments of autoimmune disorders.

Answer 30

1. In some organ-specific diseases, metabolic control is
   sufficient e.g. anti-thyroid drugs in Graves’ disease
2. Anti-inflammatory drugs - e.g. corticosteriods or non-steroidal anti-inflammatory drugs (NSAIDs)
3. Immunosuppressive drugs - e.g. cyclosporin
4. Monoclonal antibodies to blockade certain cytokines or their receptors
   e. g. Infliximab blocks action of Tumour Necrosis Factor (TNF) which Inhibits immune response and alleviates symptoms

Question 31

what alleviates symptoms of SLE?

Answer 31

Depletion of B cells by monoclonal antibodies