Zees autoimmunity, basic concept and examples

Lecture objectives:
1. Introduce areas of autoimmunity
2. Key features of immune system and autoimmunity
3. Examples of autoimmune diseases
4. Current treatment strategies
Summary points:
Immune tolerance mechanisms have evolved to reduce extent of
autoimmunity
Genetic association with many autoimmune diseases, HLA being the most
prominent association
Signs of autoimmune disease comes long after it has already occurred
No known cures for autoimmune diseases
Treatments mediate immune response, target inflammatory mediator,
block/alters immune cell function
HSCT is actively trailed for RA, MS, SLE
1. Introduce areas of autoimmunity
Adaptive immunity is simply the appropriate immune response should the
immune system be targeting a FOREIGN PATHOGEN.
When this adaptive immune system targets SELF, this is known as AUTOIMMUNITY.
Reasons why autoimmunity occur:
Body routinely selects/destroys T-cells and B-cells
o High affinity for self T/B cells are DESTROYED
o Low affinity for self T/B cells are SELECTED Positive selection
Somatic recombination
o May variations due to V-D-J joining creates many kinds of T and Bcells
Result
o System is not imperfect Some high affinity cells are not
destroyed and are released into the body
o These high affinity cells bind to self, and cause autoimmune
diseases
People get autoimmune diseases because of:
o Genetic predisposition
o Environmental factors
2. Key features of immune system and autoimmunity
Feature
Takes time before clinically
relevant

Specific immune cell causes

Explanation
Autoantibodies affect some cells and
progressively gets worse Minor effects at the
start, can get worse after exposure to
environmental triggers
(T1DM)
For specific diseases, either the antibody (e.g.

the autoimmune disease

Pathophysiology

IgE) or T-cells (CD4, CD8) are the ones that

cause the disease not the entire immune
system at fault (i.e. people do not get all
autoimmune disease, just some types!)

Type I diabetes
Targets insulin-secreting
beta cells of the islets of
Langerhans

Auto-antigens

Insulin
Protein tyrosine phosphate
IGRP

Specific immune cell

cause

CD4, CD8, B cells

Islet: CD8 T cells

Treatment

- Insulin replacement, but

increases risk of chronic
hypercycaemia and comorbidities
- Islet transplant (tissue
rejection)
- Autologous HSCT

Other stuf

Increase in number of
autoantibodies is evidence
of immune response
spreading to other targets
3. Examples of autoimmune disease
4. Current treatment strategies

Rheumatoid Arthritis
Chronic inflammatory
environment within joint;
immune cells cause
cartilage destruction
(Not known but) Collagen,
proteoglycans, heat-shock
protein
MHC presence suggests Tcell involvement
Anti-IgG rheumatoid factor
Immune complexes
(cytokines)
No cure
- Anti-TNF-a: Targets
inflammatory cytokines
combined with low dose
methotrexate
- Autologous bone marrow
transplantation

Multiple S
Event withi
to antigen p

Localised to
sheaths wh
produced b
oligodendro
CD8 cells

No cure
- Anti-VLA4
antibody tre
- Interferon
- Glatriame
mimics mye
to MHC
- Autologou
transplanta