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

Autoimmunity- Miller Flashcards

(103 cards)

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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
What are the symptoms of Phemphigus ?
Painful chronic blistering of the skin
26
How do you diagnose Phemphigus ?
Punch Biopsy of the lesion followed by immunofluorescent staining IIgG4 Ab considered pathogenic
27
How do you treat Pemphigus?
Corticosteroids and other anti-inflammatory mediators
28
What causes Graves disease ?
Antibody that bind to the thyroid stimulating hormone (TSH) receptor
29
What is an antagonist ?
A molecule that binds to receptor preventing its interaction with its specific ligand.
30
What is an agonist ?
A molecule that binds to a receptor, triggering the receptor as if it is interacting with its specific ligand
31
Describe what you think would happen if an agonist bound to a TSH receptor ?
An agonist will mimic the binding of TSH to the TSH receptor, thus the overproduction of thyroid hormone will ensue
32
What causes type 3 systemic lupus Erythematosis ?
It is mediated by autoantibodies specific for many self macromolecules ( DNA, Ribosomes, Histones ect. )
33
Describe the process of the Coomb's test | 3 Steps
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
34
What is coomb's reagent and what does it bind to ?
Coomb's reagent is an Anti-Human antibody that binds to the endogenous antibody specific for the RBC surface molecules
35
What causes Type 2 Graves disease ?
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
36
What is acute Rheumatic fever?
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.
37
What is the specific mechanism of acute rheumatic fever ?
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
38
What class of autoimmune disease is acute rheumatic fever ?
Type 2 autoimmune disease- Which is caused by antibodies specific for components of cell surfaces or the extracellular matrix
39
What are the symptoms of Acute Rheumatic Fever ? (Think we have autoantibodies binding to the heart tissue causing inflammation)
Chest Pain, Fever, Weakness, fatigue, joint pain
40
Hyperthyroidism, Heat intolerance, nervousness, irritability, warm moist skin, weight loss, enlargement of the thyroid, bulging eyes, and a characteristic stare
Graves disease - Ab's that bind to thyroid stimulatory hormone receptor and actually mimic binding of the TSH receptor
41
How do you treat Graves Disease
You will have to remove the thymus or reduce its function
42
How can you remove TSH receptor -specific antibodies?
Exchange the blood plasma
43
How is graves disease caused and what type of autoimmunity is it ?
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
What is a type 2 autoimmunity ?
Caused by antibodies specific for components of cell surfaces or the extracellular matrix
45
The signaling from nerve to muscle across the neuromuscular junction is impaired ... what is the problem ?
Myasthenia Gravis
46
What causes Myasthenia Gravis ?
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
What does Pyridostigmine do ?
Inhibits Cholinestrase which degraded acetylcholine.
48
IgG specific Gangliosides which mediate an acute inflammatory demyelination polyneuropathy ....?
Guillian Barre Syndrome
49
What is the infection that most commonly leads to GBS ?
Campylobacter
50
Symmetrical weakness of the lower limbs which rapidly ascendsto upper limbs and face combined with difficulty swallowing and breathing and drooling is also common.
Guillian Barre Syndrome
51
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 ?
Wegner's Granulomatosis
52
What causes the vasculitis portion of Wegner's Granulomatosis ?
Degranulation of neutrophils that are adhered to the vascular wall because of an up regulation of adhesion molecules
53
What will WG do to the upper airway ?
Pain, Stuffiness, nosebleeds, rhinitis, degrade the septum
54
What activates macrophages ?
INF - Gamma
55
What is the mechanism of Guilliam Barre syndrome ?
IgG specific for gangliosides (Common components of human nerve tissue) which mediate acute inflammatory demyelinating polyneuropathy (AIDP)
56
What will WG do to the airway ?
It will cause subglottal stenosis
57
Describe the mechanism of Wegner's Granulomatosis
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
What will WG do to the kidney ?
It will cause rapid progressive segmental necrotising glomerulonephritis
59
How can you treat WG ?
Plasma exchange and immunosupressants
60
What is a type 3 autoimmunity
Immune complexes get deposited in the tissues
61
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
Systemic Lupus Erythematosus
62
How does SLE work ?
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
Will SLE affect multiple tissues throughout the body ?
Yes, it is progressive and will affect blood vessels, kidneys, joints, and other tissues which will cause further initiation of inflammatory responses.
64
What is a type 4 autoimmune disease ?
It is mediated by T cells
65
What disease caused selective destruction of unsulin - producing cells in the pancreas.
Insulin dependent diabetes mellitus
66
How does IDDM actually work ?
Patients produce a T cell mediated autoimmune response that destroys the insulin producing cells in the pancreas.
67
What is the destruction of Islets of langerhans mediated by in IDDM ?
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
How do you treat IDDM ?
Daily injections of purified insuli
69
What is an autoimmune disease characterized by chronic or episodic inflammation of the joints ?
Rheumatoid Arthritis
70
How does Rheumatoid Arthritis work ?
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
What is the primary mediator of inflammation in RA patients ?
TNF-alpha
72
What are Temicade, Humira, and Enbrel ?
TNF-Alpha blockers that are used to treat RA
73
Is RA a T cell mediated disease or a B cell mediated disease
Could be both but nobody is really sure.
74
What disease is characterized by an autoimmune reaction directed at the myelin sheeth of nerves ?
Multiple Sclerosis
75
What does MS cause in the CNS ?
Sclerotic plaques of demyelinated tissue in the white matter of the central nervous system
76
What actually causes MS ?
TH1 CD4 cells are activated and cause the demyelination of the nerve cells
77
How do you treat MS ?
Immunosupressive drugs and injections of IFN-B1
78
Dry muccosal glands, no tears or saliva, dry skin nose and vagina. What is the problem
Sjogren's Syndrome
79
What happens in Sjogren's syndrome
Autoimmune destruction of the exocrine glands
80
What would you test in the blood for Sjogren ?
Anti-nuclear antibody and rheumatoid factor
81
How do you test tear production ?
The Shirmer test
82
What will a genetic absence of transcription factor AIRE cause ?
Autoimmune Polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
83
What does AIRE do ?
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
What is the most important genetic factor that can predispose a person to an autoimune disease ?
HLA antigen expression but there are literally tons of genetic factors that can be altered
85
What can physical damage to immunologically privileged sites cause ?
Autoimmune reactions.
86
What can potentially ahppen after trauma to the eye ?
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
What is a post traumatic autoimmune sensitization to eye tissue cause ?
Sympathetic opthalmia
88
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 ?
Platelet disorder. Thrombocytopenic Purpura d
89
What is purpura ?
Brusing
90
What is thrombocytopenia ?
Low Platelet Count
91
How do you treat Thrombocytopenic Purpura ?
Plasmapheresis with plasma from healthy donors
92
If you have an Ab specific for type 4 collagen which lines the basement membranes ... you have ?
Good Pasture Syndrome
93
What organ will good pastures syndrome damage ?
The kidney
94
How do you treat Good Pastures Syndrome ?
Plasma Exchange and anti-inflammatory drugs
95
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 ?
Pemphigus Vulgaris
96
What are cryoglobulins ?
Immnoglobulins that become insoluble at a lowered temperature. sometimes it can be only the light chain,
97
When are cryoglobulins produced ?
In patients who have a B cell proliferative disorder
98
What is Metzler's Triad ?
Purpura, arthralgia and myalgia
99
How can cryoglobulins cause disease ?
They act similiar to rheumatoid factor and find to the Fc region of antibody molecules.
100
What is a bence Jones Protein ?
Part of an Ab that will only precipitate the light chain in response to decreased temperature. A cryoglobulin
101
A patient presents with progressive weakness, vision impairment, spasticity and oligoclonal bands of IgG in the CSF, what is the disease ?
Multiple Sclerosis
102
How do you treat MD ?
INF-Beta
103
How do you treat Rheumatoid Arithritis ?
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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