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Common Mechanisms of Disease-2 > Autoimmunity- Miller > Flashcards

Autoimmunity- Miller Flashcards

1
Q

What is autoimmunity ?

A

Immune response directed at self antigens

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2
Q

What is an autoimmune response ?

A

Any immune response that is directed at host tissues, The effectors of the autoimmune response are autoantibodies and autoimmune T cells

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3
Q

What is autoimmune disease ?

A

Chronic disease state that results from autoimmune responses

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4
Q

What is an antagonist ?

A

An antibody that binds to a cell surface receptor thereby preventing its function

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5
Q

What is an agonist ?

A

An Ab that binds to a cell surface receptor in a way that mimics the binding of the actual ligand to the receptor.

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6
Q

How are autoimmune diseases classified ?

A

By the immunological effector that is responsible for their function

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7
Q

What do autoimmune diseases arise through ?

A

Through the breakdown of the negative selection processes that remove self-reactive T cells and B cells from the Lymphocyte repertoire

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8
Q

Are autoimmune diseases ever mediated by IgE ?

A

No, autoimmune diseases are never mediated by IgE antibodies

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9
Q

What causes autoimmune hemolytic anemia ?

A

When IgG and IgM bind to the surface of erythrocytes

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10
Q

What happens when IgM and IgG bind to an erythrocyte ?

A

The complement cascade is activated and the RBC is destroyed

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11
Q

RBC depletion results in what condition ?

A

Anemia

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12
Q

how are RBC’s cleared from circulation?

A

Bound Ab and Cb3 mediate clearance of RBC’s from circulation by phagocytes in the spleen

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13
Q

How can you confirm Cb3 clearance of RBC’s from the blood ?

A

Direct Coomb’s Hemagglutination Test

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14
Q

What is neutropenia ?

A

A decreased number of neutrophils because they have been targeted for destruction by autoimmune responses directed at surface antigens of neutrophils

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15
Q

How can you treat neutropenia ?

A

Splenectomy will reduce the destruction of WBC’s

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16
Q

What is Type 2 schleroderma ?

A

Inflammatory destruction of vascuar endothelial cells of arterioles and smooth muscle cells; replacement with collagen and other fibrous materials.

**If can also affect the kidneys blood vessels, liver, and brain

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17
Q

What are the symptoms of Schleroderma ?

A

Localized or symmetrical skin thickening; hard smooth ivory colored areas of hardened skin

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18
Q

What is required to diagnose schleroderma

A

presence of anti-nuclear Abs, anti- topoisomerase Abs, and anti-centromere Abs (IgGs)

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19
Q

How do you treat Schleroderma ?

A

No real standard treatment but giving drugs that will increase blood flow to the extremities will help

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20
Q

What causes type 2 rheumatic fever ?

A

It is caused by antibodies that are produced during response to bacterial infection ( Group A streptococcus pyrogenes)

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21
Q

What is molecular mimicry ?

A

When bacterial specific antibodies cross react with heart tissue this is known as molecular mimicry

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22
Q

What is an example of molecular mimicry ?

A

Streptoccal cell - wall components are very similiar to determinants expressed in heart tissue. Bacteria specific antibodies can bind thesee similiar determinants and cause inflammation —> this can cause heart valve scarring and myocarditis

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23
Q

What is Type 2 Pemphigus Vulgaris ?

A

Autoimmune condition by IgG specific for 2 proteins resulting in loss of cohesion in heratinocytes in the epidermis

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24
Q

Pemphigus vulgaris is mediated by which antibody ?

A

IgG

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25
Q

What are the symptoms of Phemphigus ?

A

Painful chronic blistering of the skin

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26
Q

How do you diagnose Phemphigus ?

A

Punch Biopsy of the lesion followed by immunofluorescent staining IIgG4 Ab considered pathogenic

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27
Q

How do you treat Pemphigus?

A

Corticosteroids and other anti-inflammatory mediators

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28
Q

What causes Graves disease ?

A

Antibody that bind to the thyroid stimulating hormone (TSH) receptor

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29
Q

What is an antagonist ?

A

A molecule that binds to receptor preventing its interaction with its specific ligand.

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30
Q

What is an agonist ?

A

A molecule that binds to a receptor, triggering the receptor as if it is interacting with its specific ligand

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31
Q

Describe what you think would happen if an agonist bound to a TSH receptor ?

A

An agonist will mimic the binding of TSH to the TSH receptor, thus the overproduction of thyroid hormone will ensue

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32
Q

What causes type 3 systemic lupus Erythematosis ?

A

It is mediated by autoantibodies specific for many self macromolecules ( DNA, Ribosomes, Histones ect. )

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33
Q

Describe the process of the Coomb’s test

3 Steps

A
  1. Blood sample from a patient with immune mediated heamolytic anemia ( In which human antigens are bound to the RBC surface)
  2. The patients washed RBC’s are incubated with antihuman antibodies ( Coomb’s reagent)
  3. RBC’s agglutinate: The antihuman Ab’s bind to the human Ab’s that are bound to RBC’s and the whole complex precipitates
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34
Q

What is coomb’s reagent and what does it bind to ?

A

Coomb’s reagent is an Anti-Human antibody that binds to the endogenous antibody specific for the RBC surface molecules

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35
Q

What causes Type 2 Graves disease ?

A

Greves disease is caused by antibodies that bind to the Thyroid Stimulating Hormone (TSH) receptor mimicing the binding of Thyroid hormone to the receptor —> Overproduction of TSH

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36
Q

What is acute Rheumatic fever?

A

It is a disease caused when antibodies which are produced in response to bacterial infection cross react with self antigens of the human heart and become autoantibodies.

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37
Q

What is the specific mechanism of acute rheumatic fever ?

A

Molecular Mimicry- The streptococcal cell wall constituents are very similar to some of the constituents of healthy human heart tissue. Due to this similiarity antibodies produced by the body to fight the infection bind to the healthy tissue and cause an inflammatory reaction that damages the heart tissue

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38
Q

What class of autoimmune disease is acute rheumatic fever ?

A

Type 2 autoimmune disease- Which is caused by antibodies specific for components of cell surfaces or the extracellular matrix

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39
Q

What are the symptoms of Acute Rheumatic Fever ? (Think we have autoantibodies binding to the heart tissue causing inflammation)

A

Chest Pain, Fever, Weakness, fatigue, joint pain

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40
Q

Hyperthyroidism, Heat intolerance, nervousness, irritability, warm moist skin, weight loss, enlargement of the thyroid, bulging eyes, and a characteristic stare

A

Graves disease - Ab’s that bind to thyroid stimulatory hormone receptor and actually mimic binding of the TSH receptor

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41
Q

How do you treat Graves Disease

A

You will have to remove the thymus or reduce its function

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42
Q

How can you remove TSH receptor -specific antibodies?

A

Exchange the blood plasma

43
Q

How is graves disease caused and what type of autoimmunity is it ?

A

Type 2- IT is caused by antibodies that bind to thyroid stimulatory receptors and actually mimic the binding of TSH to the receptor. The result is the massive overproduction of TSH

44
Q

What is a type 2 autoimmunity ?

A

Caused by antibodies specific for components of cell surfaces or the extracellular matrix

45
Q

The signaling from nerve to muscle across the neuromuscular junction is impaired … what is the problem ?

A

Myasthenia Gravis

46
Q

What causes Myasthenia Gravis ?

A

Autoantibodiesspeficic for acetylcholine receptors on muscle cells bind to the receptors inducing their endocytosis and degradation in lysosomes. The loss of the acetylcholine receptors leaves the muscle cell less sensitive to neuronal stimulation.

47
Q

What does Pyridostigmine do ?

A

Inhibits Cholinestrase which degraded acetylcholine.

48
Q

IgG specific Gangliosides which mediate an acute inflammatory demyelination polyneuropathy ….?

A

Guillian Barre Syndrome

49
Q

What is the infection that most commonly leads to GBS ?

A

Campylobacter

50
Q

Symmetrical weakness of the lower limbs which rapidly ascendsto upper limbs and face combined with difficulty swallowing and breathing and drooling is also common.

A

Guillian Barre Syndrome

51
Q

What is the type 2 autoimmune disease that is mediated by anti-neutrophil cytoplasmic antibodies. These ANCA’s bind to neutrophils and activate them, causing upregulation of adhesion molecules which bind to the epithelium and degranulate causing vasculitis ?

A

Wegner’s Granulomatosis

52
Q

What causes the vasculitis portion of Wegner’s Granulomatosis ?

A

Degranulation of neutrophils that are adhered to the vascular wall because of an up regulation of adhesion molecules

53
Q

What will WG do to the upper airway ?

A

Pain, Stuffiness, nosebleeds, rhinitis, degrade the septum

54
Q

What activates macrophages ?

A

INF - Gamma

55
Q

What is the mechanism of Guilliam Barre syndrome ?

A

IgG specific for gangliosides (Common components of human nerve tissue) which mediate acute inflammatory demyelinating polyneuropathy (AIDP)

56
Q

What will WG do to the airway ?

A

It will cause subglottal stenosis

57
Q

Describe the mechanism of Wegner’s Granulomatosis

A

What is the type 2 autoimmune disease that is mediated by anti-neutrophil cytoplasmic antibodies. These ANCA’s bind to neutrophils and activate them, causing upregulation of adhesion molecules which bind to the epithelium and degranulate causing vasculitis ?

58
Q

What will WG do to the kidney ?

A

It will cause rapid progressive segmental necrotising glomerulonephritis

59
Q

How can you treat WG ?

A

Plasma exchange and immunosupressants

60
Q

What is a type 3 autoimmunity

A

Immune complexes get deposited in the tissues

61
Q

What autoimmune disease is caused by autoantibodies specific for many intracellular macromolecules present in all cells in the body. Characterized by a facial rash, spontaneous abortion and a positive serum syphilius test

A

Systemic Lupus Erythematosus

62
Q

How does SLE work ?

A

Autoantibodies bind to cell surface components initiating inflammatory reactions that lead to tissue destruction. The dammaged cells will release soluble macromolecules and immune complexes that will be deposited in blood vessels, kidneys, and joints causing initiation of inflammatory responses.

63
Q

Will SLE affect multiple tissues throughout the body ?

A

Yes, it is progressive and will affect blood vessels, kidneys, joints, and other tissues which will cause further initiation of inflammatory responses.

64
Q

What is a type 4 autoimmune disease ?

A

It is mediated by T cells

65
Q

What disease caused selective destruction of unsulin - producing cells in the pancreas.

A

Insulin dependent diabetes mellitus

66
Q

How does IDDM actually work ?

A

Patients produce a T cell mediated autoimmune response that destroys the insulin producing cells in the pancreas.

67
Q

What is the destruction of Islets of langerhans mediated by in IDDM ?

A

IDDm patients produce CTL’s specific for an undefined protein component of B islet cells, IDDM patients also produce antibodiesand T cells that are specific for a numberof the products of B islet cells.

68
Q

How do you treat IDDM ?

A

Daily injections of purified insuli

69
Q

What is an autoimmune disease characterized by chronic or episodic inflammation of the joints ?

A

Rheumatoid Arthritis

70
Q

How does Rheumatoid Arthritis work ?

A

Affected joints hace a characteristic leukocyte infiltrate that includes CD4 and CD8 T cells, B cells, plasma cells, neutrophils, and macrophages; the inflammatory responses result in tissue damage

71
Q

What is the primary mediator of inflammation in RA patients ?

A

TNF-alpha

72
Q

What are Temicade, Humira, and Enbrel ?

A

TNF-Alpha blockers that are used to treat RA

73
Q

Is RA a T cell mediated disease or a B cell mediated disease

A

Could be both but nobody is really sure.

74
Q

What disease is characterized by an autoimmune reaction directed at the myelin sheeth of nerves ?

A

Multiple Sclerosis

75
Q

What does MS cause in the CNS ?

A

Sclerotic plaques of demyelinated tissue in the white matter of the central nervous system

76
Q

What actually causes MS ?

A

TH1 CD4 cells are activated and cause the demyelination of the nerve cells

77
Q

How do you treat MS ?

A

Immunosupressive drugs and injections of IFN-B1

78
Q

Dry muccosal glands, no tears or saliva, dry skin nose and vagina. What is the problem

A

Sjogren’s Syndrome

79
Q

What happens in Sjogren’s syndrome

A

Autoimmune destruction of the exocrine glands

80
Q

What would you test in the blood for Sjogren ?

A

Anti-nuclear antibody and rheumatoid factor

81
Q

How do you test tear production ?

A

The Shirmer test

82
Q

What will a genetic absence of transcription factor AIRE cause ?

A

Autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy (APECED)

83
Q

What does AIRE do ?

A

Induces expression of tissue-specific proteins in the thymus and if they are not expressed there will not be negative selection in the thymus

84
Q

What is the most important genetic factor that can predispose a person to an autoimune disease ?

A

HLA antigen expression but there are literally tons of genetic factors that can be altered

85
Q

What can physical damage to immunologically privileged sites cause ?

A

Autoimmune reactions.

86
Q

What can potentially ahppen after trauma to the eye ?

A

Proteins from the eye can drain into the lymph nodes where they are presented to T cells. If an autoimmune reaction developes CD8 cells will attack and destroy tissue in either eye.

87
Q

What is a post traumatic autoimmune sensitization to eye tissue cause ?

A

Sympathetic opthalmia

88
Q

If you have IgG mediated inhibition of an enzyme responsible for cleavage of vWF what does the patient have ? Is this a clotting disorder or a platelet disorder ?

A

Platelet disorder. Thrombocytopenic Purpura d

89
Q

What is purpura ?

A

Brusing

90
Q

What is thrombocytopenia ?

A

Low Platelet Count

91
Q

How do you treat Thrombocytopenic Purpura ?

A

Plasmapheresis with plasma from healthy donors

92
Q

If you have an Ab specific for type 4 collagen which lines the basement membranes … you have ?

A

Good Pasture Syndrome

93
Q

What organ will good pastures syndrome damage ?

A

The kidney

94
Q

How do you treat Good Pastures Syndrome ?

A

Plasma Exchange and anti-inflammatory drugs

95
Q

What is an autoimmune condition mediated by IgG speficic for 2 proteins (Desmogelein 1 and 3 ) which results in loss of cohesion in Keratinocytes in the epidermis ?

A

Pemphigus Vulgaris

96
Q

What are cryoglobulins ?

A

Immnoglobulins that become insoluble at a lowered temperature. sometimes it can be only the light chain,

97
Q

When are cryoglobulins produced ?

A

In patients who have a B cell proliferative disorder

98
Q

What is Metzler’s Triad ?

A

Purpura, arthralgia and myalgia

99
Q

How can cryoglobulins cause disease ?

A

They act similiar to rheumatoid factor and find to the Fc region of antibody molecules.

100
Q

What is a bence Jones Protein ?

A

Part of an Ab that will only precipitate the light chain in response to decreased temperature. A cryoglobulin

101
Q

A patient presents with progressive weakness, vision impairment, spasticity and oligoclonal bands of IgG in the CSF, what is the disease ?

A

Multiple Sclerosis

102
Q

How do you treat MD ?

A

INF-Beta

103
Q

How do you treat Rheumatoid Arithritis ?

A

Anti-TNF antibody (Inflixamab)

ADCC mediated Destriction of B cells producing the autoantibody (Rituximab)

Common Mechanisms of Disease-2 (24 decks)

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