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Immunology 12: Autoimmune Diseases Flashcards

1
Q

Breakdown of mechanisms responsible for self tolerance and induction of an immune response against components of self

A

Autoimmunity

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2
Q

Both _____ and __________ can be involved in the damage in autoimmune diseases

A

Antibodies and effector T cells.

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3
Q

List 9 features of autoimmune diseases?

A

1- genetic predisposition.
2- higher incidence among females.
3- occur more in older individuals.
4- occurrence of more than one type of autoimmune disorders in an individual.
5- usually non-reversible.
6- an elevated level of Igs.
7- deposition of Igs or their derivatives at particular sites like glomeruli.
8- accumulation of lymphocytes and plasma cells at site of lesion.
9- benefit from corticosteroids or their immunosuppressive therapy.

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4
Q

List the mechanisms of autoimmunity?

A

1- gene susceptibility.
2- infection.
3- environmental factor.

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5
Q

List the 3 roles of gene susceptibility?

A

1- HLA genes “disease - associated alleles”.
2- non-HLA gene defects.
3- single gene mutation.

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6
Q

Where are HLA genes located?

A

Within MHC.

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7
Q

List the roles of HLA genes?

A

1- regulate the development of autoimmunity.
2- critical role in T cell maturation.
3- critical role in the induction of immune response.
4- responsible for auto-antigen processing and presentation.

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8
Q

Give an example of HLA in SLE, Type 1 DM, Rheumatoid arthritis, thyroiditis, ankylosing spondylitis?

A

SLE = DR2/ DR3.
T1DM = DR3/ DR4.
Rheumatoid arthritis = DR4.
Thyroiditis = DR5.
Ankylosing spondylitis = B27.

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9
Q

What is the mechanism of HLA genes in autoimunity? And what does it lead to?

A

Presence of MHC defects, lead to:
1- affect the negative selection of T cells in they thymus.
2- affect the development of regulatory T cells.

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10
Q

Give 2 examples of Non-HLA gene defects that cause autoimmunity?

A

1- polymorphism in a gene called PTPN-22 (most frequently implicated with RA and T1DM).
2- polymorphism in the gene for NOD-2 (NOD-2 is a cytoplasmic sensor of microbes) Crohn’s disease.

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11
Q

Give an example of an autoimmune disease caused by a single point mutation?

A

Multiple sclerosis.

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12
Q

List the ways infections can cause autoimmunity?

A

1- up-regulate the expression of co-stimulators of APCs (via drugs, microorganisms).
2- molecular mimicry: some microbes may express Ags that have same amino acid sequences as self-antigens.
3- some viruses (EBV & HIV): polyclonal B-cell activation, which may result in production of autoantibodies.
4- infection induce tissue injury > release hidden Ag > lead to “not tolerant” T cell activation.
5- cytokines induced by infections that recruit lymphocytes > self-reactive lymphocytes, to sites of self antigens.

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13
Q

Give examples of molecular mimicry?

A

1- M protein of S.pyogenes: cardiac myosin.
2- Rubella: Type 1 DM.
3- Campylobacter: Guillan-Barre syndrome.

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14
Q

Give examples of environmental factors that cause autoimmunity?

A

Hormonal influences.
Radiation.
Trauma.

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15
Q

Give an example of hormonal influences that affects an autoimmune disease?

A

SLE affects women 10 times more than men.

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16
Q

List the 3 classification of autoimmune diseases?

A

1- systemic.
2- organ specific.
3- both.

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17
Q

Define: the auto-immunity is directed against an antigen that is present at many different sites and involve serval organs?

A

Systemic autoimmune diseases.

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18
Q

Define: the auto-immunity is directed against an antigen of one organ?

A

Organ specific (localized) autoimmune diseases.

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19
Q

List autoimmune diseases that are localized (organ specific) that affect blood cells?

A

1- Hemolytic anaemias.
2- Thrombocytopenias.
3- Pernicious anaemia.
4- Polyarteritis nodosa.

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20
Q

List autoimmune diseases that are localized (organ specific) that affect endocrine glands?

A

1- Grave’s disease.
2- Juvenile DM.
3- Addison’s disease.

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21
Q

List autoimmune diseases that are localized (organ specific) that affect neuromuscular?

A

1- Myasthenia gravis.
2- Multiple sclerosis.

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22
Q

List autoimmune diseases that are localized (organ specific) that affect the GIT?

A

1- Celiac disease.
2- Inflammatory bowel disease (IBS).
3- Autoimmune hepatitis.
4- Primary biliary cirrhosis.

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23
Q

List autoimmune diseases that are localized (organ specific) that affect dermatological?

A

1- Psoriasis.
2- Vitiligo.
3- Alopecia aerata.
4- Sjogren’s syndrome.

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24
Q

List the autoimmune diseases that are systemic (non-organ specific)?

A

1- SLE.
2- Rheumatoid arthritis.
3- Goodpasture’s syndrome.
4- Scleroderma.
5- Dermatomyositis.

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25
List the classification of autoimmune diseases (other than localized and systemic)?
1- Diseases mediated by antibodies and immune complexes. 2- Diseases mediated by T cells.
26
List organ specific diseases mediated by antibodies and immune complexes?
1- Autoimmune hemolytic anemia. 2- Grave’s disease. 3- Addison’s disease. 4- Myasthenia gravis. 5- Goodpasture’s syndrome.
27
List systemic autoimmune diseases mediated by antibodies and immune complexes?
1- SLE. 2- Rheumatoid arthritis.
28
List the autoimmune diseases caused by reaction to microbial Ag and are mediated by antibodies and immune complexes?
1- Polyarteritis nodosa.
29
List organ specific autoimmune diseases mediated by T cells?
1- Type 1 DM. 2- Multiple sclerosis.
30
List systemic autoimmune diseases mediated by T cells?
1- SLE. 2- Sjogren syndrome.
31
List the autoimmune diseases caused by reaction to microbial Ag and are mediated by T cells?
1- Inflammatory myopathies. 2- Inflammatory bowel disease (IBS).
32
What happens in autoimmune hemolytic anemias?
Antibodies against RBCs, RBCs coated with Abs are prematurely destroyed in the spleen and liver.
33
What are the 2 groups of autoantibodies that affect autoimmune hemolytic anemias?
Cold and warm autoantibodies.
34
What are cold autoantibodies?
Complete Abs, IgM class. Agglutinate RBCs at 4C (not at 37C).
35
What are warm autoAbs?
Incomplete Abs, IgG class. Detected by direct coombs test (coat RBCs).
36
Where are warm autoantibodies seen?
In patients taking drugs like sulphonamides, antibiotics, and alpha methyl dopa.
37
Define: Abs bind to RBCs or bacteria but does not produce agglutination?
Incomplete Abs.
38
List hemolytic autoimmune diseases?
1- autoimmune hemolytic anemias. 2- autoimmune thrombocytopenia. 3- autoimmune leucopenia. 4- pernicious anemia.
39
What happens in autoimmune thrombocytopenia?
Auto-Abs against platelets: idiopathic thrombocytopenic purpura.
40
What happens in autoimmune leucopenia?
Anti-leucocyte Abs seen in the serum of patients with SLE and RA.
41
What happens in pernicious anemia?
Caused by a lack of vitamin B12.
42
List the 2 types of auto antibodies that are present un pernicious anemia?
1- Abs against the parietal cells of the gastric mucosa — atrophic gastritis, achlorhydria. 2- Abs against the intrinsic factor (IF) — prevents Vit.B12 absorption.
43
List the autoimmune disorders of the endocrine disorders?
1- Insulin dependent (type 1 or juvenile) DM. 2- Addison’s disease. Autoimmune diseases of the thyroid gland: 3- Hashimoto’s thyroiditis. 4- Thyrotoxicosis (grave’s disease).
44
What happens in Insulin dependent (Type 1 or Juvenile) DM?
Autoimmunity and destruction of cells of islets of langerhans in pancreas by T cells — insufficient insulin production.
45
What happens in Addison’s disease?
Antibodies to the cells of Zona Glomerulosa layer of adrenal glands.
46
What hormone do adrenal glands produce? And what do they do?
They produce the hormone cortisol, which: - maintain blood pressure and heart function. - balance the effects of insulin breaking down sugar food energy.
47
What happens in hashimoto’s thyroiditis?
Destruction of thyroid follicles. Hypo-functioning thyroid. Goiter (enlarged thyroid).
48
What happens in thyrotoxicosis (grave’s disease)?
Antibodies attach to receptors on thyroid gland and stimulate production of thyroid hormone. Symptoms: Goiter (enlarged thyroid) and bulging eyes.
49
List autoimmune neuromuscular disorders?
1- Myasthenia gravis. 2- Multiple sclerosis (MS).
50
What happens in myasthenia gravis?
Abs against acetylcholine receptors on myoneural junctions of striated muscle - prevents binding of Ach to its receptor.
51
What is multiple sclerosis (MS)?
A chronic disease that affects the brain and spinal cord (CNS).
52
What happens in multiple sclerosis (MS)?
Destruction of myelin sheath of axons by immune cells. Messages moving along the nerve are transmitted more slowly or not at all which slows or blocks muscle coordination, visual sensation and other nerve signals.
53
What are the causes of MS and where is it most often seen?
Causes may include genetic and environmental factors. Most often seen between ages of 20 and 50.
54
How do we diagnose MS?
CSF is tested for levels of immune system proteins and for the presence of oligoclonal bands. (Oligoclonal bands (Dark bands) = MS)
55
List the GIT autoimmune disorders?
1- celiac disease. 2- Inflammatory bowel disease. 3- autoimmune hepatitis. 4- primary biliary cirrhosis (PBC)
56
What is celiac disease?
A permanent sensitivity to gluten in genetically susceptible individuals (e.g. wheat). Only treatment for celiac disease is a gluten - free diet (GFD).
57
List the 2 types of IBS?
1- Ulcerative colitis: chronic inflammation of large intestine (colon). 2- Crohn’s disease: chronic inflammatory disease of the intestines between the mouth and the anus.
58
What are Crohn’s disease and ulcerative colitis characterized by?
Enhanced recruitment of effector macrophages, neutrophils and T cells into the inflamed intestine, where they are activated and release pro-inflammatory cytokines.
59
What is autoimmune hepatitis?
Body’s immune system attacks liver cells, causing inflammation of the liver (hepatitis), if untreated lead to cirrhosis (scarring and hardening) of the live > liver failure.
60
What is primary biliary cirrhosis (PBC)?
A chronic disease characterized by: Progressive inflammation and destruction of the small bile ducts within the liver.
61
Disease progression of PBC is delayed with what treatment?
Progression delayed with coticsoteriods treatment to reduce inflammation.
62
What are the antibodies associated with PBC?
1- anti-mitochondrial antibodies (AMA) occurs in over 90% of PBC cases. 2- autoantibodies to two nuclear antigens: Gp-210 and Sp 100.
63
List autoimmune dermatological disorder?
1- scleroderma. 2- dermatomyositis. 3- psoriasis. 4- vitiligo. 5- alopecia aerata. 6- vesiculo-bullous disorders. 7- sjogren’s syndrome.
64
What happens in psoriasis?
There is excessive growth of the new cells underneath the layer of skin.
65
What happens of vitiligo?
The cells that give pigment to the skin are destroyed leading to formation of white de-pigmented patches.
66
What happens in alopecia areata?
Immune system attacks hair follicles or the roots of the hair.
67
What happens in vesiculo-bullous disorders?
Blistering disease of the skin.
68
What happens in sjogren’s syndrome (SS)?
Production of antibodies against glands of body (lacrimal and salivary glands) > combination of dry eyes and dry mouth. Occurs secondary to RA, SLE or other autoimmune disorders.
69
List autoimmune diseases of the eye?
1- phacoanaphylaxis: autoimmune response to the lens protein following cataract surgery. 2- sympathetic ophthalmia in opposite eye: following perforating injuries of the eye, involving ciliary body and iris.
70
What is autoimmune orchitis?
Lymphocytic infiltration of testes and circulating Abs to the sperms and germinal cells. Follows mumps orchitis.
71
What is SLE?
Chronic, generalized immune disorder due to loss of control of both humoral and CMI response.
72
The autoantibodies in SLE react against what?
DNA, blood cells, neurons and other tissues. When cells die, immune complexes form and deposit under skin, joints, kidneys, blood vessels and CNS.
73
Patients in SLE die from what?
Die from kidney damage.
74
Which complements are predisposed in SLE?
HLA-DR2 or DR3.
75
How do we diagnose SLE?
Antinuclear Ab.
76
What is RA?
Symmetric polyarthritis with muscle wasting, finger and joint deformities, and subcutaneous nodules. Associated with myocarditis, vasculitis and other disseminated lesions.
77
What is the cause of RA?
Unknown but microbial mimicry may be involved. B cells in the joints produce autoantibodies against collagen that covers joint surfaces. IgM autoantibodies (rheumatoid factors, RF) against IgG form complexes in joint, leading to inflammation and cartilage damage.
78
What happens in Goodpasture’s syndrome?
Renal disease + lung hemorrhage, Antibodies react with antigens in the glomerular basement membrane of the kidney > severe necrosis. Antigen in kidney is similar to antigen found in lungs, resulting in antibody reacting with lung tissue > pulmonary hemorrhage.
79
How do you diagnose goodpasture’s syndrome?
Sputum test and kidney biopsy.
80
What is scleroderma?
Scar tissue in the skin and organs of the body. This leafs to thickness and firmness of involved areas.
81
List the 2 types of scleroderma?
1- diffuse. 2- limited.
82
What is diffuse scleroderma?
Involves symmetric thickening of skin. Rapidly progress to hardening of inflamed. Organ disease can occur early on and be serious. Organs affected include the esophagus, bowels, lungs with scarring (fibrosis), heart, and kidneys.
83
What is limited scleroderma?
Often confined to the skin of the fingers and face. Progress is more slowly than in diffuse form. Also called the CREST varint of scleroderma.
84
what is polymyositis?
A disease of muscle fiber inflammation, involved muscles are usually closest to the trunk of the body. - weakness of muscles. - loss of strength- difficulty getting up from chairs, climbing stairs or lifting above the shoulders.
85
What is dermatomyositis?
Skin involvement. - eyes can be surrounded by a violet discoloration with swelling. - scaly reddish discoloration over the knuckles, elbows and knees (gottron’s sign). - reddish rash on the face, neck and upper chest.
86
What are transitory autoimmune diseases?
- Follow certain infections or drug therapy. - infecting agent or drug induces antigenic alteration in some self Ags. - transient: undergo spontaneous cure when the infection is controlled or the drug is withdrawn.
87
What do transitory autoimmune diseases include?
Anemia, thrombocytopenia, or nephritis.
88
What is mixed connective tissue disease (MCTD)?
Overlap of 3 diseases: SLE, scleroderma, polymyositis.
89
In MCTD we get high serologic quantities of what?
1- antinuclear antibodies (ANAs). 2- antibodies to ribonucleoprotein (anti-RNP).
90
What is the goal of treatment of autoimmune diseases?
Reduce symptoms and control the autoimmune response.
91
List the 4 types of treatment used in autoimmune diseases?
1- anti-inflammatory drugs: aspirin, corticosteroids. 2- immunosuppressive drugs: cyclophosphamide, cyclosporine. 3- plasmapheresis to remove immune complexes and antibodies. 4- induction of tolerance and anti-co-stimulators (CD40L and B7) are under trail.
92
Which of the following immunoglobulins do cold autoantibodies involve in hemolytic autoimmune diseases? A. IgA B. IgE C. IgM D. IgG
C. IgM.
93
Which of the following known as systemic (non-organ-specific) autoimmune disease? A. Goodpasture’s syndrome B. Grave’s disease C. Vitiligo D. Sjogren’s syndrome
A.

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