Auto-Immunity In Endocrine Disease

Front 1

Mechanisms of tolerance

Back 1

1. Deletion of auto-reactive T cells in the thymus
2. Control of activation of T cells
- requirement for co-stimulation: CD28-B7
3. Regulatory T cells inhibit auto-reactive T cells
- CD25+ CD4+ T cells:
- Treg express transcription factor FoxP3
- Gene mutation in foxP3 results in auto-immune endocrine disease (XPID)

Front 2

IPEX syndrome caused by failure of T regulatory cell development

Back 2

•
X-linked recessive inheritance
•
Immunodysregulation
-
severe eczema and high IgE
-
evidence of abn Th2 responses
•
Polyendocrinopathy
-
diabetes,
-
evidence of abn Th1 responses
•
Auto-immune haemolytic anaemia
•
Enteropathy & severe diarrhoea

Front 3

Envirnomental precipitator of A/I

Back 3

•
Precipitated by interaction of environmental factors with genetic susceptibility
–
Infection eg. viral infection pancreas
–
Drug, eg Interferon therapy for Hepatitis C and auto-immune thyroid disease
–
Smoking in RA; anti-cyclic citrullinated peptide (a-CCP) antibodies: (citrullinated arginine)

Front 4

Frequency of anti-thyroid & anti-nuclear auto-antibodies increase with age

Back 4

accumulation of autoantibodies as u age
- autoantibodies DONT equal disease (sometimes theyre non-pathogenic)

Front 5

Spectrum of Autoimmune diseases

Back 5

Front 6

Hashimoto's thyroiditis

Back 6

Targer Antigen: TPO (thyroid peroxidase) & TG (thyroglobulin)

MECH: Activated T cells mainly
Ab-diagnostic

CLINICALLY: Goitre
Hypothyroidism

THYROID: looks burnt out

Front 7

Hashimoto’s thyroiditis Histology

Back 7

tertiary immune tissue (in RA, sjorgens, thyroids...)

Front 8

Thyroid microsomal antibodies

Back 8

immunofluroscent assay
- BALCK= follicle
- epithileal cells light up due to anti-thyroid antibodies

Front 9

Rates of hypo/hyper thyroid in women by age

Back 9

Front 10

Primary myxoedema

Back 10

Target Ag: TSH-R
Mech: Blocking Ab to TSH-R
Clinical Effect: Hypothyroidism

Here it BLOCKS

acts as an agonist
- stimulating the cells
GRAVES disease

Front 11

Graves' disease

Back 11

Target Ag: TSH-R
Mech: Stimulating Ab to TSH-R
- cross reactive Tc with Ag in extraocular muscles
Clinical Effect: Hyperthyroidism
- goitre
- opthalmopathy

Front 12

Extraocular opthalmopathy

Back 12

Opthalmopathy showing periorbital oedema, chemosis, sceral injection and proptosis. Lid retraction is obscured by oedema

Front 13

Graves Histology

Back 13

Front 14

Localised dermopathy

Back 14

dermopathy assoc. with eye disease
(all due to Tc cross-reactivity )

GRAVES

Front 15

Neonatal Thyrotoxicosis

Back 15

this doesnt happen now because thyrotosicosis during pregancy is an emergency (using B-blockers to switch off the effects)

- because the TSH IgG from mum is released into the neonate

Front 16

AUTO-IMMUNE DIABETES MELLISTUS

Back 16

Front 17

Auto-immune destruction of pancreatic islet in Diabetes Mellitus

Back 17

infiltrate into the pancreas
- not till >50% of the islets are destroyed till u get glucose tolerance

Front 18

AUTO-IMMUNE ADRENAL DISEASE

Back 18

Front 19

Hypo-parathyroidism

Back 19

sensor for Ca levels
Normally Ca falls Parathyroid switched on adn Ca released from the bones

Front 20

Pernicious Anaemia
Vitiligo

Back 20

Front 21

1. Diagnosis: Of endocrine Autoimmunity

Back 21

Front 22

2. Treatment of Auto-immunity endocrine disease

Back 22

Front 23

3."Prevention" of auto-immune diseases

Back 23

REQUIREMENTS:
• Early recognition.
• e.g. anti-islet cell antigen (ICA) antibody in first degree relatives of patients with IDDM
INTERVENTION:
•Block auto-immune process
•Inhibit or deviate auto-immune T cells
•Without risk to relatives