Core Immunology - Autoimmune Diseases (9) Flashcards
Autoimmunity
Theoretical concept, inherit to immune system, genetically determined
Autoimmune disease
Breakdown of self-tolerance, environmental factors acting on favourable genetic background
MHC class
Class 2 shape T cell repertoire, predispose to autoimmunity, antigen presenting cells MHC class 2 present antigens to CD4 and T cells
Which MHC class do all cells have?
1 - present antigens to CD8 and T cells
Where’s most common genetic susceptibility?
HLA region
Autoimmunity arise due to
Failures of central/peripheral tolerance, B/T cells require receptor so can react against any infection, any possible combination, some will react to self proteins
Risk factors
Women, elderly, sequestered antigens, infection, trauma-tissue damage, smoking
How does autoimmunity cause disease?
- Autoreactive B cells and autoantibodies (cytotoxic, activation of complement, interfere with normal physiological function)
- Autoreactive T cells (directly cytotoxic and inflammatory cytokine production)
- Infections active immune and autoimmune response
Changes in amount/nature of autoantigens
- Citrullination of proteins (RA)
- Tissue transglutamase alters gluten bind to HLA-DQ (coeliac)
- Failure to clear apoptotic debris increases availability of sequestered antigens inside cell (SLE)
T cells > inflammation
Releasing inflammatory cytokines/helping B cells make autoantibodies
Organ specific
Affect a single organ, overlap with other organ specific diseases
Example of organ specific
Thyroid disease
Systemic
Affect several organs, autoantigens found in most cells, overlap with non-organ specific diseases
Examples of systemic
Connective tissue diseases
Hashimotos thyroiditis
Destruction of thyroid follicles, autoantibodies to thyroglobulin and thyroid peroxidase
Hashimotos thyroiditis leads to …thyroidism
Hypothyroidism
Grave’s disease
Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
Grave’s disease leads to leads to …thyroidism
Hyperthyroidism
Myasthenia gravis symptoms
Difficulty keeping eyes open, speaking, swallowing, hardly smiles, muscular weakness with atrophy
Myasthenia gravis mechanism
Antibody sticks to receptor for acetylcholine at synapse - stopping it
Folic acid/B12 deficiency
Pernicious anaemia, B12 binds IF, tingling in feet, increase fatigue, vitiligo
SLE symptoms
Photosensitive malar/butterfly rash (sunlight damages DNA), multiple mouth ulcers, arthralgia, alopecia, fatigue, arthritis, chest pleuracy, pleural effusion, cerebral lupus, seizures and strokes
Anti-nuclear antibodies
In SLE immune system forms antibodies against proteins and DNA in nuclei of cells, bind to skin cells that have been damaged by UV, ANA form immune complexes that bind to the complement and cause inflammation
Connective tissue diseases
SLE, scleroderma, polymyositis, Sjogrens syndrome
Vasculitis
Inflammation of small vessels
Symptoms of vasculitis
Patchy non-blanching rash, sinus problems, ear pain
Antibody Anti-Neutrophil Cytoplasmic Antibodies (ANCA)
Inflammation of vessel wall caused by WBC stimulated by ANCA, digest neutrophils by covering them in enzymes
3 forms of ANCA vasculitis
- Microscopic polyangitis (MPA)
- Granulomatis with polyangitis (GPA)
- Eosinophilic granulomatous with polyangitis (EGPA)
Granuloma
Mass of inflammed tissue - destructive lesions in nose, sinuses, trachea, lung, orbits
Polyangitis
Inflammation of many vessels - skin, kidney, lung, gut
Wegener’s Granulomatosis
Granulomatosis with polyangitis
Raynaud’s phenomenon symptoms
Painful, white, numb fingers (red and throbbing when warm up)
Primary Raynaud’s phenomenon
Common young women, runs in families, ANA negative, harmless
Secondary Raynaud’s phenomenon
ANA positive (anti-centromere/anti-scl-70 antibodies), associated with scleroderma and SLE
Scleroderma
Skin fibrosis and tightening, digital ulcers due to tightening and ischaemia, lung fibrosis - gut/kidneys
