Mind Map by sophie_connor, updated more than 1 year ago
Created by sophie_connor over 6 years ago


Immunology Mind Map on Autoimmunity, created by sophie_connor on 05/23/2013.

Resource summary

1 Autoimmunity
1.1 When the immune system loses sense of self and attacks and destroys healthy body tissue
1.2 A destructive immune response against self antigens
1.3 Once started, difficult to stop
1.4 Severity ranges from minor to lethal
1.5 Affects 5-7% of the population
1.6 Can affect any organ or organ system in the body
1.7 Autoantibodies can be passed from mothers to their babies
2 Autoimmunity vs. hypersensitivity
2.1 Immunogen in hypersensitivity is an allergen, in autoimmunity it's an autoantigen
2.2 Hypersensitivity causes a clinical allergy, autoimmunity causes an immune disorder
2.3 10% of the population experience hypersensitivity, 5% experience autoimmunity
2.4 Mortality by hypersensitivity is rare, but in autoimmunity it is high
2.5 Mechanisms in hypersensitivity include type I, II, III and IV, in autoimmunity type II, III and IV
3 What causes autoimmunity?
3.1 Failure to maintain self-tolerance
3.2 Risk factors
3.2.1 Genetic susceptibility Presence of susceptible genes Being female Could be due to imbalance in hormone levels Rise in hormones associated with pregnancy may cause abortion of the foetus Endometriosis and preeclampsia are thought to be autoimmune in nature ORE: oestrogen response elements There isn't a single pin-pointable gene Numerous genes involved in susceptibility
3.2.2 Environmental triggers Infections Injury Drugs, toxins, UV radiation Stress, poor diet, lack of exercise, lack of sleep, abuse of alcohol and use of tobacco
4 Exceptions to the rule: simple genetic autoimmune illnesses
4.1 Autoimmune polyglandular syndrome type I (APS-1)
4.1.1 Gene: AIRE Knockout causes decreased expression of self antigens in the thymus, resulting in defective selection of self reactive T cells
4.1.2 Mechanism: decreased expression of self antigens in the thymus resulting in a defect in negative selection
4.2 Immunodysregulation polyendocrinopathy enteropathy,X linked (IPEX)
4.2.1 Gene: FOXP3 Knockout causes decreased function of CD4 CD25 regulatory T cells
4.2.2 Decreased generation of regulatory T cells
4.3 Autoimmune lymphoproliferative syndrome (ALPS)
4.3.1 Gene: FAS Knockout causes failure of apoptotic death of self reactive B and T cells
4.3.2 Failure of apoptotic death of self reactive T or B cells
5 MHC association
5.1 Mechanisms underlying the association of MHC alleles with various autoimmune diseases are still not clear
5.2 Association with MHC class II genes
5.3 MHC may present a self peptide and activate pathogenic T cells
5.4 MHC may influence negative selection of developing T cells
6 Genetics of autoimmunity
6.1 NOD2
6.1.1 Polymorphism associated with 25% of Crohn's disease
6.1.2 Microbial sensor
6.2 PTPN22
6.2.1 Most common autoimmunity associated gene
6.2.2 Phosphatase
6.3 CD25
6.3.1 Associated with MS
6.3.2 Role in regulatory T cells
7 Injury
7.1 Sympathetic opthalamaia
7.1.1 Physical trauma in one eye can initiate autoimmune response to both eyes
7.1.2 Eye anterior chamber is an immune privileged site
7.1.3 Normally autoimmune antigens in this site are not exposed to the immune system
7.1.4 Trauma to one eye results in the release of sequestered introcular protein antigens Released intraocular antigens are carried to the lymph node and activate T cells Effector T cells return via bloodstream and attack antigen in both eyes On occasion this causes blindness in both damaged and undamaged eyes
8 Superantigens
8.1 Several infectious agents contain antigens with the ability to polyclonally activate a subset of CD4+ T cells bearing particular VB TCR families
8.1.1 Hypothesis: this may activate auto antibodies This would increase VB in autoimmune lesions Isolated reports in rheumatoid arthritis and diabetes No strong evidence
8.1.2 Polyclonal activation Viruses and bacteria can induce non-specific polyclonal B cell activation leading to autoantibodies Gram negative bacteria, cytomegalovirus and EBV are polyclonal activtors SLE patients produce large quantities of IgM polyclonal antibodies Systemic Lupus Erythematosus (SLE) can attack any part of the body resulting in inflammation or tissue damage
9 Local infections
9.1 Induces inflammation which results in activation of non-professional APC
9.2 Thyroid cells do not normally express MHC class II
9.2.1 IFN-gamma produced during infection or non-specific inflammation induces MHC class II expression on thyroid cells Activated T cells recognise peptides presented by MHC class II and induce autoimmune thyroid disease
9.3 Hashimoto thyroiditis
9.3.1 Follicular cells of the thyroid
9.4 Type I diabetes
9.4.1 beta cells of islets of Langerhans
10 Molecular mimicry
10.1 Some viruses and bacteria possess antigenic determinants that are identical or similar to normal host cell components
10.2 The same MHC molecule presents both a pathogen peptide and a self peptide that mimics it
10.2.1 Naive T cell is activated by the pathogen peptide present by the MHC molecule Effector Th1 cells responds to the self peptide mimic and activates the macrophage causing inflammation
10.3 Examples
10.3.1 Rheumatic fever
10.3.2 Multiple sclerosis
10.3.3 Type I diabetes
10.3.4 Systemic Lupus erythematosus
10.3.5 Post rabies encephalitis Used to develop in individuals that had the rabies vaccine Rabies virus was grown in rabbit cell culture that contained antigens from rabbit brains In vaccinated people these antigens would induce formation of antibodies and activated T cells which would cross react with the recipient's own brain cells causing encephalitis
11 Epitope spreading
11.1 Once autoimmune diseases begin they tend to be progressive with remissions and exacerbations
11.2 A mechanism for chronic progression
11.3 In a persistent microbial infection and tissue damage, initial response to one self epitope expands to involve additional epitopes on the same molecule as well as additional self proteins
11.3.1 Explains how one epitope can mature into full blown autoimmune response
11.4 Release of sequestered antigen
11.4.1 APC with cross reacting Ag (molecular mimicry) Inappropriate MHC expression on non-APCs Activated macrophages from activated T helper cells cause inflammation and local Delayed Type Hypersensitivity (IV) resulting in tissue damage Activated Th cell produces B cells which produce plasma cells by polyclonal activation that produce Abs to self antigens resulting in tissue damage
12 Autoimmunity classification
12.1 Organ specific autoimmune diseases
12.1.1 Type I diabetes
12.1.2 Goodpasture's syndrome Autoantibodies specific for antigens in the basement membranes of the kidney and the alveoli of the lungs Leads to complement activation and direct cellular damage as well inflammatory response mediated by the build up of complement split products Tissue damage leads to kidney damage and pulmonary haemorrhage Smoking can be the trigger because it damages alveoli and exposes collagen
12.1.3 Multiple sclerosis
12.1.4 Grave's disease
12.1.5 Hashimoto's thryoiditis
12.2 Systemic autoimmune diseases
12.2.1 Rheumatoid arthritis
12.2.2 Scleroderma
12.2.3 Systemic lupus erythematosus
13 Autoimmune diseases of the endocrine glands
13.1 Insulin dependent diabetes mellitus
13.1.1 Type 1
13.1.2 T cells attack and destroy insulin producing cells (beta cells) located in the islets of Langerhans
13.1.3 The pancreas does not produce or properly use insulin and consequently increased levels of blood glucose
13.1.4 Islets of Langerhans contain several cell types secreting distinct hormones, each cell expresses different tissue specific proteins In IDDM an effector T cell recognises peptides from the beta cell specific protein and kills the beta cell Glucagon and somatostatin are still produced by the alpha and delta cells but no insulin can be made
13.1.5 Treated with daily insulin injections
13.1.6 Factors involves in the destruction of beta cells Activated CTLs migrate to the islets and begin to attack the beta cells Cytokine production released during response: IFN-y, TNF-a and IL-1 Coxasckie virus group B- direct destruction of the beta cells by the virus as a result of molecular mimicry
13.2 Chronic thyroiditis: Hasimoto's disease
13.2.1 Production of autoantibodies and sensitised to Th1 cells specific for thyroid antigens
13.2.2 Intense infiltration of the thyroid gland by lymphocytes, macrophages and plasma cells
13.2.3 Binding of autoantibodies against thyroid tissue proteins interferes with the iodine uptake and leads to decreased production of thyroid hormones
13.2.4 Treatment: oral administration of thyroid hormone
13.3 Hyperthyroidism: Graves' disease
13.3.1 Autoantibodies produced against the thyroid gland
13.3.2 Long acting thyroid stimulating antibody causes unregulated overproduction of thyroid hormones
13.3.3 Symptoms Heat intolerance Nervousness Irritability Warm, most skin Thyroid enlargement
13.3.4 Treatment Thyroidectomy Destruction of thyroid by radioactive 131I
13.3.5 Autoantibodies can be passed from mothers to their babies Mother with Graves disease makes anti-TSHR antibodies During pregnancy antibodies cross the placenta into the foetus Newborn infant also suffers from Graves' disease Plasmapheresis removes maternal anti-TSHR antibodies and cures the infant's disease
14 Myasthenia Gravis
14.1 Blocks normal binding of acetylcholine and mediates complement mediated degradation of receptors
14.1.1 Binding autoantibodies to the acetylcholine receptors on the motor end plates of muscles
14.1.2 Progressive weakening of the skeletal muscles and loss of muscle control
14.2 Symptoms
14.2.1 Drooping eyelids
14.2.2 Inability to retract the corners of the mouth
15 Systemic autoimmune diseases
15.1 Defects in immune regulation
15.2 Response is directed towards a broad range of target antigens and involves a number of organs
15.3 Tissue damage is widespread by...
15.3.1 Cell mediated immune responses
15.3.2 Direct cellular damage caused by autoantibodies
15.3.3 Accumulation of immune complexes
15.4 Celiac disease
15.4.1 Wheat flour gluten peptide specific CD4 T cells
15.4.2 Gluten is degraded in the gut lumen to give a resistant fragment Gluten fragment enters the gut tissue and is deaminated by transglutaminase Naive CD4 T cells respond to deaminated peptides presented by MHC II Inflammatory effector T cells cause villous atrophy
15.5 Systemic Lupus Erythematosus (SLE)
15.5.1 Appears in women age 20-40
15.5.2 More prevalent in females
15.5.3 Symptoms Low grade fever Ulcers Aching muscles Arthritis Fatigue Loss of appetite Butterfly rash on face Poor circulation
15.5.4 Antinuclear antibodies directed against DNA, nucleoprotein, histones and nucleolar RNA IgG against a wide variety of cellular constituents (defect in maintenance of B cell self tolerance Binding of antibodies to cell surface antigens causes inflammatory responses leading to cell and tissue destructon Immune complexes, deposited in blood vessels, kidney, joints and other tissues cause tissue inflammation and destruction
15.5.5 Damage occurs by... Formation of immune complexes Type III hypersensitivity Antibody mediated injury to blood cells Type II hypersensitivity
15.5.6 Gene: C1q Knockout causes defective clearance of immune complexes and apoptotic cells
15.6 Rheumatoid arthritis
15.6.1 Mostly affects women age 40-60
15.6.2 Major symptom: chronic inflammation of joints
15.6.3 B cells in joints produce IgM autoantibodies called rheumatoid factors This binds to Fc region of normal circulating IgG, forming IgM-IgG complexes that are deposited in the joints and activate the complement cascade Type III hypersensitivity reaction which leads to chronic inflammation of the joints
15.7 Multiple sclerosis
15.7.1 Autoimmune neurological disease
15.7.2 Symptoms may be mild such as numbess in the limbs or severe such as paralysis and loss of vision
15.7.3 Most people are diagnosed between the ages of 20 and 40
15.7.4 Autoreactive Th1 cells in the cerebrospinal fluid induce expression of chemokines and cytokines that recruit inflammatory cells Inflammatory lesions along the myelin sheath of nerve fibres Treated with immunosuppressive drugs
15.7.5 Possible environmental influence and genetic infleunce
15.7.6 Cause unknown, possibly a virus
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