Autoimmunity

Question 1

utoimmune polyglandular syndrome type 1 (APS-1), AIRE

Answer 1

low expression of some self antigens in thymus – some autoreactive T cells not deleted.

Question 2

Autoimmune lymphoproliferative syndrome (ALPS) FAS, FASL

Answer 2

failure of apoptosis of some self reactive T and B cells.

Question 3

what is tolerance

Answer 3

the process that keeps the immune system from attacking “self”

Question 4

delusional Tolerance (recessive)

Answer 4

• self reactive T cells are deleted in the thymus, however occasional these self-reactive T cells may escape deletion and travel to the periphery
• In the periphery they can cause tissue damage

Question 5

regulatory tolerance

Answer 5

• T cell specific for self antigen becomes a regulatory T cell (Treg)
• cytokines (IL-10 and TGF-beta) produced by Treg inhibit other self-reactive T cells

Question 6

Mechanisms thought to be involved in breakdown of tolerance

Answer 6

• Failure to delete autoreactive lymphocytes
• Central or peripheral tolerance failure
• Molecular mimicry
• Abnormal presentation of self antigens
• Aberrant expression of HLA class II molecules
• Release of sequestered self antigens
• Overproduction of self antigens
• Cyptic T cell epitopes
• Epitope spreading

Question 7

Rheumatic fever

Answer 7

a classic example of molecular mimicry

Question 8

pathology of rheumatic fever

Answer 8

• Group A Streptococcus infection, typically in throat
• Antibodies generated against Strep carbohydrate GlcNAc
• These antibodies cross react on cardiac myosin
• T cells also produced
• Heart valve damage, but also brain/neuronal damage possible

Question 9

Systemic Lupus Erythematosus (SLE)

Answer 9

• Butterfly rash
• Raised red patches on skin
• Light sensitivity
• Mouth ulcers
• Heart/lung lining inflammation
• Seizures/nerves problems
• Proteinuria
  ANA - antinuclear antibodies

Question 10

Grave’s disease

Answer 10

• Overstimulation of thyroid

* Antibodies generated against TSH receptor which mimics TSH

Question 11

Hashimoto’s thyroiditis

Answer 11

• Autoimmune hypothyroidism
• Antibodies to thyroglobulin and thyroid peroxidase
• Fatigue, feeling cold, TSH increase, weight gain, enlarged thyroid

Question 12

Myasthenia Gravis

Answer 12

• Antibodies to acetylcholine receptors
• Long-term neuromuscular problems
• Double vision (diplopia), drooping eyelids (ptosis) and other face muscles
• Skeletal muscle weakness, esp after exercise

Question 13

Autoimmune Pernicious Anemia

Answer 13

• Autoimmune condition affecting stomach
• Antibodies generated to intrinsic factor,and parietal cells
• Deficiency in vitamin B12 results as no binding to intrinsic factor and absorption

Question 14

Autoimmune hemolytic anemia

Answer 14

• Antibodies binding to rbc
• Lysis, clumping, clearance by spleen
• Induced by drug or agent modifying rbc cell surface, neo-antigen created.
• Symptoms – chills, tachycardia, pale, fatigue dark urine, jaundice

Question 15

Foot and Ankle, Knee:

Answer 15

Effusions and synovial thickening of the knee usually are detected easily.

Question 16

Hip

Answer 16

involvement is common in RA, but early manifestations are not apparent.

Question 17

Hands and Wrists:

Answer 17

affected in virtually all people with RA.

Question 18

Elbow

Answer 18

Effusion difficult to detect on physical exam. Only objective finding is loss of motion.

Question 19

Shoulders:

Answer 19

Neck stiffness and general loss of motion

Question 20

Diagnosis of RA

Answer 20

•Lab tests
–Imaging studies – Erythrocyte Sedimation Rate

–Blood tests – C-reactive Protein (CRP)

–Rheumatoid factor – Antinuclear Antibodies (ANA)

Question 21

treatments for rheumatoid arthritis

Answer 21

–relieving pain
–reducing inflammation
–stopping or slowing joint damage
–improving functioning and sense of well-being

Question 22

coeliac disease

Answer 22

• HLA class II link – DQ 2.5 (most common), DQ8 and DQ2.2 (less common)