Autoimmunity

Question 1

What is autoimmunity?

Answer 1

The immune system recognises self structures as foreign and attacks it, which results in a hypersensitivity disease

Question 2

What is the cause of autoimmunity?

Answer 2

Failure of immune tolerance to self cells

Question 3

What is an autoimmune disease due to?

Answer 3

Development of autoantibodies and or self reactive antigen. No cure - treatment is symptomatic

Question 4

Layers of self tolerance

Answer 4

Central tolerance - positive/negative selection
Peripheral - anergy, antigen segregation and regulatory immune cells
Combination of factors can cause tolerance mechanisms to be broken, bypassed or evaded. Failure of tolerance creates self reactive b and T cells

Question 5

What are the multiple factors involved in autoimmunity development?

Answer 5

Genetic predisposition eg HLA genes
Environment eg viral infections and lifestyle factors
Immunological education
Gender - maybe hormones?

Question 6

Disease pathogenesis of autoimmunity

Answer 6

Antigen driven
Autoreactive B and T cells are activated by autoantigens

Question 7

Why are autoreactive B and T cells activated by auto antigens?

Answer 7

They have not been encountered before
They are present in novel form
They are at higher concentrations
They are in an environment that supports lymphocyte activation

Question 8

Autoimmune mechanisms initiated by infection or trauma

Answer 8

Disruption of cell or tissue barrier
Binding of pathogen to self protein
Molecular mimicry

Question 9

Molecular mimicry

Answer 9

Molecular similarity of microbial antigen and self antigen

Question 10

Bystander activation

Answer 10

Activation of unrelated T cells in an antigen independent way during an infection with normal activation of antigen specific T cells

Question 11

Type II hypersensitivity autoimmunity

Answer 11

Auto antibodies
Bind self cells (sometimes with complement) and mediate damage via opsonisation
Form immune complexes together with antigen - activate complement which releases inflammatory mediators
Modulate or block host cell function

Question 12

2nd example of type II hypersensitivity

Answer 12

Myasthenia gravis
Blocking of receptor by autoantibodies - inhibiting effect.
Antibodies against acetylcholine receptor. Acts as an antagonist - blocks binding to receptor. Block of neuromuscular synapse, causing no muscle contraction.
Genetic component HLA-DR3 alleles

Question 13

Symptoms of myasthenia gravis

Answer 13

Severe muscle weakness
Difficulty chewing, swallowing, breathing

Question 14

Type IV hypersensitivity

Answer 14

Cell mediated
Th1 cells direct cytotoxicity via cytotoxic t lymphocytes, macrophages, cytokines.
In some cases other T cells involved

Question 17

Type II hypersensitivity example

Answer 17

Graves’ disease
Hyper stimulation of receptor due to auto antibody binding
Antibodies against hormone receptor TSH activate the receptor - causes over active thyrotropin receptor - leading to uncontrolled hormone production/ hyperthyroidism

Question 18

Symptoms of Graves’ disease

Answer 18

sweating, tremor, goitre, arrhythmia, tachycardia, nausea, diarrhoea, muscle weakness

Question 19

Type III hypersensitivity

Answer 19

Deposition of immune complexes in tissues - blood vessel walls, synovial membrane of joints, glomerular basement membrane
Activation of classical complement pathway and initiation of inflammation
Magnitude depends on number of immune complexes
Causes recruitment of neutrophils - releases granula and lytic enzymes cause tissue damage

Question 20

Example of type III hypersensitivity

Answer 20

Systemic lupus erythematosus
Chronic, multiorgan disease
Affects predominantly women.
Auto antibodies against self DNA/RNA, histones, RBCs, platelets, leukocytes and clotting factors.
Complement mediated lysis of cells causes anaemia and thrombocytopenia
Accumulation of immune complexes along walls of small blood vessels.

Question 21

Systemic lupus erythematosus symptoms

Answer 21

Fever
Weakness
Arthritis
Skin rashes
Pleurisy - pain when breathing due to inflammation of the airways
Kidney dysfunction

Question 22

Example of type IV hypersensitivity

Answer 22

Rheumatoid arthritis - female to male ratio is 3:1
Immune attack on joints - erosion of cartilage and bone
Driven by activated T cells and mediated by fibroblasts and macrophages
Also presenter of immune complexes within synovial tissues - feature of type III

Question 23

Symptoms of RA

Answer 23

Erosion of cartilage and bone
Fever
Weight loss
Fatigue
Numbness
Lung fibrosis

Question 24

Example 2 of type IV hypersensitivity

Answer 24

Psoriasis
Autoreactive Th17, Th22 cells against skin antigens
Inflammation of upper layers of skin and joints
White scaly plaques
Treatment is topical Vitamin D, anti inflammatories

Question 25

Example 3 of type IV hypersensitivity

Answer 25

Multiple sclerosis Cell mediated immune attack in CNS - brain spinal cord optic nerve Reaction against myelin (unknown if self antigen or not) Destruction of myelin leads to neurodegeneration Central role for CD4+ T helper cells, macrophages, cytotoxic T cells. Priming phase (initial trigger) not well understood (could be multi factorial, vitamin D deficiency, genetics?)

Question 26

Symptoms of MS

Answer 26

Fatigue Cognitive impairment Depression Unstable mood Weakness muscle Muscle spasms Ataxia Bowel and urinary incontinence Optic neuritis

Question 27

Treatment for autoimmune disease

Answer 27

General immunosuppresion eg corticosteroids Immune modulation eg natalizumab for MS Plasmapheresis - plasma exchange to remove auto antibodies IV-Ig - antibodies that block the auto antibody (auto ag needs to be known) Autologous stem cell transplant Metaabolic control if organ specific eg insulin