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Flashcards in Tolerance and autoimmunity Deck (44)
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What type of immune response is involved in autoimmunity?
Hence, state which cell type is always involved in autoimmunity?

Adaptive immune response with specificity for self “antigens” (autoantigens)



What proportion of people have lymphocytes with the capability of recognising self-antigens?

ALL of us – this is normal autoimmunity


What factors cause the breakdown of self tolerance which results in the transition from normal autoimmunity to autoimmune disease?

Genetic susceptibility
Environmental factors


What are the criteria for disease to be ‘autoimmune’?

- Evidence of disease-specific adaptive immune response
- Passive transfer of autoreactive cells or antibodies replicates the disease
- Elimination of the autoimmune response modifies disease
- History of autoimmune disease (personal or family), and/or MHC associations


Give more details on the genetic/environmental factors associated with autoimmune diseases.

Sex - women more susceptible
Diet - obesity, high fat, effects on gut microbiome
Microbiome - perturbation may help trigger autoimmune disease


Why are autoimmune conditions chronic?

Because self-tissue is always present


The effector mechanisms in autoimmunity resemble those of which type of immune reaction?

Hypersensitivity reactions (types 2, 3 and 4)

*Mechanisms are the same as in normal responses against foreign antigens (both B cells (antibody) and T cells can be involved)


What proportion of people affected by autoimmune disease are female?

Approx. 80%
( note that this changes between diseases)


What is a possible reason for the increase in incidence of autoimmune disease?

Hygiene hypothesis


List examples of important autoimmune diseases

Rheumatoid Arthritis
Type I diabetes
Multiple Sclerosis
Systemic Lupus Erythematosus (SLE)
Autoimmune thyroid disease (ATD)


The description of autoimmune reactions in humans is based on...?

- Organs affected
- Involvement of what specific autoantigens
- Types of immune responses


Describe the pathophysiology of autoimmune haemolytic anaemia.

There are autoantibodies against red blood cells, which bind to red blood cells and activate complement
This results in clearance and complement-mediated lysis of the autologous erythrocytes


What is a type II hypersensitivity reaction?

Antibody response against cellular or ECM antigens (insoluble antigens)


What is a type III hypersensitivity reaction?

Immune complex formed by antibody against soluble antigen (tend to be more systemic than type 2)


What is a type IV hypersensitivity reaction?

T cell mediated disease – delayed type hypersensitivity


Give important examples of type 2 hypersensitivity autoimmune diseases.

Autoimmune haemolytic anaemia
Goodpasture's syndrome
Grave's disease
Myasthenia gravis
Pemphigus vulgaris


In Goodpasture’s syndrome, IgG antibodies bind to what autoantigen? What does this result in?

IgG antibodies bind to the non-collagenous domain of basement membrane type IV collagen in the glomerulus.
This results in deposition of autoantibodies in the renal corpuscle and activation of complement => neutrophil infiltration and kidney damage


State the autoantigen in Grave's disease

TSH receptor


State an important type 3 hypersensitivity autoimmune disease. What are the autoantigens?

Systemic Lupus Erythematosus (SLE)

e.g. DNA, histones, ribosomes


As well as complement, how else do type II and type III immune reactions recruit inflammatory cells?

Inflammatory cells are recruited via the binding of inflammatory cells to the Fc portion of antibodies via their Fc receptors


Give three important examples of type 4 hypersensitivity autoimmune diseases.
What T cells can be involved?

Insulin-dependent diabetes mellitus
Rheumatoid arthritis
Multiple Sclerosis

Cytotoxic (CD8+) and helper (CD4+) T cell responses
can be involved


What is the autoantigen in multiple sclerosis?

Myelin basic protein


Recall the normal T-cell response to antigens.

T-cell receptor of T-helper cell binds to antigen presented on MHC II (by APC), with co-stimulation by its CD4 receptor.
T-cell receptor of cytotoxic T-cell binds to antigen presented on MHC I (by APC), with co-stimulation by its CD8 receptor.


What is the dominant genetic factor affecting susceptibility to autoimmune disease?

HLA class II alleles


What did the freemartin cattle and experiment show about tolerance?

It showed that early exposure to foreign antigens allows the development of tolerance to those specific antigens


Define immunological tolerance.

The acquired inability to respond to an antigenic stimulus


What are the main features of immunological tolerance?

It is acquired
It is antigen specific
It is an active process in neonates, the effects of which are maintained throughout life


What are the two types of immunological tolerance?

Central Tolerance (happens during lymphocyte development)
Peripheral Tolerance


What are the three main mechanisms of peripheral tolerance?

- anergy
- active suppression (regulatory T cells)
(- immune privilege, ignorance of antigen)


Describe the selection process for T-cells in the thymus which explains central tolerance (of T-lymphocytes)

Those that are useless – don’t recognise MHC at all => die by apoptosis

Those that are useful – associate weakly with MHC => receive signal to survive (“Positive selection”)

Those that are dangerous – associate too strongly with MHC => receive signal to die by apoptosis (“Negative selection”)