Session 3 - Lecture 1 - Autoimmunity Flashcards
1 - Autoimmunity
1 - Autoimmunity
“Overview - not going into details, will take too long. Find out what treatment there is although we do not really understand what causes it”
2 - Learning objectives
Learning objectives
- Definition of autoimmunity vs autoimmune diseases
- Understand the difference between organ specific and non organ specific autoimmune disease
- Recognize the clinical evidence that supports a role of autoimmunity in the pathogenesis of autoimmune disease
- Briefly describe the causes and mechanisms of autoimmunity and the current and future therapeutic strategies
“1. not always the same thing
- Autoimmune disease can be specific to an organ in theory, but not always the case, and non-organ specific autoimmune disease is a challenge to actually manage: means non-specific therapeutic target.
- Pay particular attention to this part – important to understand to properly managing it.
- Speculate causes of autoimmunity – should be interesting because we don’t know exactly what causes it.”
3 - Define autoimmunity and autoimmune disease
Key definitions
Autoimmunity: Immune response against the host due to the loss of immunological tolerance of self-antigen(s)
Autoimmune disease: Disease caused by TISSUE DAMAGE or DISTURBED PHYSIOLOGICAL RESPONSES due to an auto-immune response (!)
“2 key definitions to remember
1. in other words, host developed an immune response against self-antigen which it shouldn’t. That in itself isn’t a problem, pregnant woman develop Abs again RBCs; as we age, we develop Abs against nuclear proteins – defining feature of systemic non-organ specific disease – so having autoimmune Ab or self-reactive T/B cells is not an issue – it’s when it starts the process of
2 damaging the tissue or changing the physiological response which is when you have an autoimmune disease. So autoimmune disease is also stated by damage but also change in function, depends on type of hypersensitivity you are going to have against this self-antigen.”
4 - How can autoimmune disease be divided?
Clinical patterns of autoimmune disease
Autoimmunity --> Autoimmune disease {
- Organ specific: One or multiple self antigens within one SINGLE organ or tissue
- Non-organ specific: Wide distributed self antigens THROUGHOUT the body
}
Multiple systems
• Nervous disease
• Respiratory disease
• Endocrine disease
• Joint diseases
• Hematological disease
“Organ specific: one or MULTIPLE self-antigens but only located in one specific organ. Clin mngmnt will be completely diff.
Non-organ specific: therapeutic challenge, burden for the pt – rely on non-specific treatment bc immune reaction mostly in non-organ specific.
NB: Simple classification, situation not always that simple – have some organ specific with a systemic component and same pt organ specific, multiple organ also affected, during course of autoimmune disease.
But whether organ or non-organ specific, there is not going to be a single system that is not going to be affected by autoimmune diseases. So as you can see, autoimmune disease involves any organ system – this is important, will depend on outcome of hypersensitivity reaction.”
5 - Common autoimmune diseases and their target autoantigens
Diseases / Self antigen
Organ specific
Hashimoto’s thyroiditis / Thyroid peroxidase and thyroglobulin
Type 1 diabetes mellitus* / Pancreatic islet cells
Multiple sclerosis / Myelin sheath (nerve fibers)
Goodpasture’s disease / Glomerular/alveolar basement membrane (kidney)
Addison’s disease / Steroid-21 hydroxylase (adrenal cortex)
Graves’ disease / Thyroid-stimulating hormone receptor
Myasthenia gravis / Acetylcholine receptor (neuromuscular junction)
Pernicious anaemia* / Intrinsic factor (terminal ileum)
Non-organ specific
Autoimmune haemolytic anaemia / Red blood cells antigens
Rheumatoid arthritis / Rheumatoid Factor (Fc portion of the IgG)
Systemic lupus erythematosus (SLE)/ Double stranded DNA (dsDNA) + other nuclear proteins (histones)
Sjogren’s syndrome / Nuclear antigens (Ro and La)
*Multiple autoantigens may also be present in tissues
“As you can see – diff type of self antigen – could be a type of enzyme e.g. thyroid peroxidase involved in thyroid organ production. The same organ, thyroid, can be affected, can express 2 diff self-antigens for example, Grave’s disease, where the self-antigen is a receptor. So we have an enzyme we have a receptor, but diff clin outcome. Self-antigen can also be a receptor in myasthenia gravis - this is the AChR important in NMJ. Also have some in the nerve, CNS, myelin sheath affected – important to transmit electric impulse through nerves. You also have some soluble receptor factors, intrinsic receptor factors.
Finally also have cell surface proteins such as RBCs – rhesus positive and negative examples, but also other autoimmunity against different RBCs antigens. Ra is due to Fc portion of Ig, diff self-antigen. Also have self-antigen inside the nucleus, important for systemic, such as SLE and Sjogren’s syndrome – as form of dsDNA or other nuclear proteins. This also presents in Sjogren’s syndrome – v important to remember these 2 diseases (SLE and SS), these 2 are more prevalent in UK compared to rest of world, we don’t know why, SLE and Sjogren’s most prevalent in UK and US, might be environmental factor, but please remember bc keep coming back.
Issue as well, will have pt with RA who will develop SS and this will complicate a lil bit the diagnostic approach to disease. SLE is also associated with certain forms of AHA, so you can see there is a cross-interaction between diff type of autoimmune diseases, which at the end has to be taken into account if you want proper diagnosis.
NB: Some diseases will have multiple self-antigen in specific organs, just shown you the major one – other ones, some will be clinically important, others, will not. “
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