Autoimmune Diseases

Question 1

What are the 2 types of autoimmune disease?

Answer 1

Organ specific
(brain, thyroid, muscle, stomach, adrenal, pancreas)
Non-organ specific (muscle, kidney, skin, joints)

Question 2

What is IPEX syndrome?

Answer 2

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome
knockout and mutation (scurfy) in Foxp3 gene
decreased function of CD4, CD25 regulatory T cells

Question 3

What has flow cytometry revealed about CD4+ populations?

Answer 3

CD25+ and Foxp3 and Tregs make up approx. 5-7% of CD4+ population in normal individuals

Question 4

How do regulatory T cells work?

Answer 4

(i) inhibitory cytokines
(ii) cytolysis
(iii) metabolic disruption
(iv) targeting dendritic cells

Question 5

What is SLIT and what has it demonstrated?

Answer 5

Sublingual immunotherapy

dust mite improves mild-moderate atopic dermatitis

Question 6

Give an example of an organ specific autoimmune disease

Answer 6

Pemphigus vulgaris
blistering disease in epidermis
often fatal before systemic corticosteroids became available
often begins with erosions of oral mucosa

Question 7

What do histology samples of Pemphigus vulgaris show?

Answer 7

loss of normal epithelial cell adhesion and detachment of cells
suprabasal acantholysis

Question 8

Give 3 examples of skin blistering diseases

Answer 8

(i) pemphigus foliates of the stratum granulosum
(ii) pemphigus buglers of desmosomes
(iii) bulloses pemphigoid of the basal lamina (hemi-desmosomes)

Question 9

What is Fogo Selvagem?

What therapy can be used?

Answer 9

Endemic form of pemphigus foliaceus
antoantibodies used, anti-Dsg1
observed in specific river valleys or rural Brazil
association with insect bites
therapy - steroids in combination with immunosuppressive drugs (Rituximab, aCD20)

Question 10

What is lupus erythematosus?

Answer 10

systemic autoimmune, multisystem disorder
typically affects young women
autoantibodies to nuclear antigens include:
(i) ANA, ds DNA
(ii) ENA, Ro and others

Question 11

What are trigger factors for chronic discoid lupus erythematosus?

Answer 11

(i) UV light (9-11.1.07, UVA)
(ii) infection
(iii) exposure to cold
(iv) stress

Question 12

What are the clinical manifestations of neonatal lupus erythematosus?

Answer 12

transplacentally acquired

i) skin rash
(ii) congenital atrioventricular block
(iii) thrombocytopenia
(iv) leukopenia
(v) anaemia

Question 13

What are the 3 stages to molecular mimicry?

Answer 13

(i) MHC molecule presents both pathogen and self peptide
(ii) naive T cell is activated by pathogen peptide on MHC
(iii) effector Th1 cell responds to self-peptide mimic and activates a macrophage causing inflammation

Question 14

What is ALPS and what is it caused by?

Answer 14

autoimmune lymphoproliferative syndrome
Ipr/Ipr;gld/gld mutants in FAS gene
failure of apoptotic death of self-reactive B and T cells

Question 15

What kind of mutants can cause SLE (and what is it?)

Answer 15

systemic lupus erythematosus
knockout mutants in C1q gene causes SLE

IL-8 induces apoptosis in LE HPK
HPK from these patients produce TNFalpha upon stimulation with IL-18

Question 16

What therapy and prevention techniques can be used in lupus erythematosus?

Answer 16

no therapy treats the 'cause' of the disease
prevention includes:
(i) protection from UV light
(ii) chloroquin (hydroxy)
(iii) immunosuppression