Tolerance & Immunity Flashcards

(74 cards)

1
Q

What is clonal deletion?

A

Self reactive cells are killed by apoptosis in bone marrow and thymus
Constitue central tolerance

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2
Q

What is anergy?

A

Self reactive cells are alive but cannot respond

Constitue peripheral tolerance

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3
Q

How is autoimmunity achieved?

A

Failure to delete self reactive B and T cells in the bone marrow and thymus
Reactivation of anergic self reactive B and T cells

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4
Q

What are the steps of T cells thymic education?

A

Pro T cells enter subcapsular as double negative ( no CD4 or CD8)
DN move to cortex and become double positive(DP) express CD4 and CD8
DP go through a positive selection
If selected DP go through a negative selection
DP become single positive

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5
Q

What is the mechanism of positive selection?

A

DP cells bind to MHC 1 and 2
DP with moderate affinity to self MHC survive the selection
DP with too high or too low affinity for self MHC die by apoptosis

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6
Q

What is the mechanism of negative selection?

A

Positively selected DP move to corticomedullary junction, increase expression of TCR and interact with interdigitating dendritic cells (IDC)
IDC express thymic self antigens
Cells that recognize self antigens die
Cells that do not recognize self antigens survive

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7
Q

What is the second part of the negative selection?

A

Surviving cells move to the medulla and interact with medullary epithelial cells
Medullary epithelial cells express non thymic self antigens under the control of AIRE
Cells that recognize non thymic self die
Cells that do not survive

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8
Q

What is autoimmune polyendocrine syndrome 1?

A

Defect in the AIRE gene causing autoreactive cells to not be deleted

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9
Q

What are the symptoms of APS-1?

A
Chronic mucocutaneous candidiasis 
Alopecia
Vitiligo
Hypoparathyroidism
Adrenal insufficiency 
Thyroiditis
Type 1 diabetes
Ovarian failure
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10
Q

How does tolerance is induced in Treg cells?

A

Some T cells recognize self antigens in the thymus but do not die
Instead T cells develop CD 25+ regulatory T cells

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11
Q

What are the functions of Treg cells?

A

Protect host from self reactive lymphocytes by secreting IL-10 and TGF beta
Down regulate B7 co stimulatory molecule on dendritic cells
Suppress TH1,TH2,TH17 and macrophages

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12
Q

How is anergy induced in T cells?

A

T cell interacts with an APC that lack B7
B7 is a co stimulatory molecule on APCs
Most body cells lack B7 so tolerance to self issue is the norm

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13
Q

What are the immunological privilege tissues?

A
Brain
Anterior chamber of the eye
Placenta 
Pregnant uterus 
Testis
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14
Q

What is the mechanism of B cell selection?

A

No T cell help lead to B cell being anergic
Immature B cell binds to self antigen in bone marrow can be deleted or go through receptor editing
Immature B cells binds to a soluble self antigen can go through anergy or through receptor editing

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15
Q

What are the factors influencing autoimmunity ?

A

Inheritance of HLA and other susceptibility genes
Environmental: infection ( molecular mimicry), injury,inflammation
Physical trauma that breaks immunological privilege
Gender: females more affected than males

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16
Q

What are the diseases associated with HLA-B27?

A

Psoriasis
Ankylosing spondylitis
Inflammatory bowel disease
Reiters syndrome

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17
Q

What are the diseases associated with HLA-DR2?

A

Multiple sclerosis
Systemic lupus erythematous
Goodpasture syndrome
Hay fever

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18
Q

What are the disease associated with HLA-DR3/DR4?

A

Type 1 diabetes

HLA-DR4- Rheumatoid arthritis

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19
Q

What are the characteristics of pernicious anemia?

A

Megaloblastic anemia caused by vitamin B12 (cobalamin) malabsorption organ target is the stomach
Molecular target is intrinsic factor
Cellular target is parietal cells
Associated with chronic H.pylori infection
Type 2 hypersensitivity

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20
Q

What is the presentation of a patient with pernicious anemia?

A

Usual onset40-70 years
Weakness, sore tongue, paresthesia
Beefy red tongue appearance
Increase risk of gastric adenocarcinoma (3x)

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21
Q

How is pernicious anemia diagnosed?

What is the treatment ?

A

Circulating antibodies to intrinsic factor and other parietal cell components
Treated with vitamin B12

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22
Q

What are the characteristics of Goodpasture syndrome ?

A

Organ targets are the lungs and the kidneys
Glomerulonephritis and pulmonary hemorrhage
Complement fixing antibodies against type 4 collagen (molecular target)
Type 2 hypersensitivity

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23
Q

What is the presentation of Goodpasture syndrome?

A

Onset: 20-30 and 60-70 years old
Smoking and solvent inhalation is a precipitating event
Pulmonary hemorrhage can lead to respiratory failure and eventually death

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24
Q

How is Goodpasture syndrome diagnosed?

A

Detection of circulating anti glomerular basement membrane antibodies
Kidney biopsy shows linear deposition of antibody and complement
HLA-DR2 linkage

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25
What is the treatment for Goodpasture syndrome?
Acute phase: intubation, assisted ventilation, hemodialysis Long term: plasmapheresis, high dose corticosteroids, immunosuppression with cyclophosphamide, reduce exposure to irritants ESRD: hemodialysis, kidney transplant
26
What are the characteristics of type 1 diabetes?
Insulin dependent Cell mediated killing of beta cells (cellular target) of pancreas (organ target) GAD is the molecular target Type 4 hypersensitivity
27
What is the presentation of type 1 diabetes patient?
``` Most common in juveniles Thin stature despite good appetite Hyperglycemia Ketoacidosis RuQ pain from fatty liver ```
28
How is type 1 diabetes diagnosed?
Presentation and history Fasting glucose tests greater than 5mg/dL in an asymptomatic patient Any random glucose test greater or equal 200 mg/dL with symptoms Circulating autoantibodies to insulin and beta cell components
29
How is type 1 diabetes treated?
Symptoms are treated with insulin | Diet and exercise will help control the disease
30
What are the characteristics of Myasthenia gravis?
IgG autoantibodies form against acetylcholine receptors at neuromuscular junctions Only skeletal muscles are affected Symptoms do not appear until acetylcholine receptors reduced to less than 30% of normal Type 2 hypersensitivity
31
How does a patient with myasthenia gravis present?
Onset is 28 years in women and 42 in men Progressive muscle weakness with exercise Strength is recovered after a period of rest Weakness least severe in the morning Ptosis Worsened with sunlight, stress ans medications
32
What is neonatal myasthenia?
Generalized muscle weakness in infants born to myasthenia gravis women Due to IgG passively crossing the placenta Symptoms resolve in days to weeks as antibody titers decline
33
How is myasthenia gravis diagnosed?
Circulating anti acetylcholine receptor antibodies Thymoma on Xray or CT Administration of edrophonium resolves symptoms
34
What is the treatment for myasthenia gravis?
``` Cholinesterase inhibitors Corticosteroids Immunosuppressive drugs Intravenous immune globulin Plasmapheresis Thymectomy ```
35
What are the characteristics of Addison disease?
Adrenocortical insufficiency when 90% of adrenal cortices are destroyed Inadequate secretion of corticosteroids Mixed type 2 and 4 hypersensitivity
36
How is the presentation of a patient with Addison disease?
Most common in children and females Adult onset 30-50 years Hyperpigmentation of skin and mucous membranes Overproduction of corticotropin and melanocyte stimulating hormone Vitiligo Acute adrenal crisis
37
How is Addison disease diagnosed and treated ?
Rapid ACTH stimulation test shows no rise in plasma cortisol and aldosterone after ACTH injection Treated with hormone replacement ie prednisone
38
What are the characteristics of Bullous pemphigoid?
Chronic subepithelial blistering skin disease Rarely involves mucous membrane IgG antibodies are specific for the hemidesmosomal antigens BPAg1 and 2 Exacerbated by UV, Xray, NSAIDs, antibiotics
39
How does a patient with bullous pemphigoid present?
Average age is 65 years | Blisters are tense and preceded by urticaria
40
How is bullous pemphigoid diagnosed?
DIF shows IgG and complement in linear band at demal epidermal junction IgG id on blister roof Circulating antibodies to BPag1 and 2
41
How is bullous pemphigoid treated?
Prednisone Immunosuppressives Tetracycline Rituximab
42
What are the characteristics of of pemphigus vulgaris?
Erosion of skin and mucous membanes | IgG are specific for keratinocyte surface desmogleins
43
How does a pemphigus vulgaris patient present?
Mean age is 50-60 years Flaccid blisters are painful but do not itch Treatment similar to bullous pemphigoid
44
What are the characteristics of Graves disease?
Autoimmune disease characterized by hyperthyroidism Autoantibodies against receptor to TSH continuously stimulate thyroid Type 2 hypersensitivity
45
How is Graves’ disease presentation?
``` Goiter Exophthalmos/proptosis Pretibial myxedema Heat intolerance Tachycardia Weight loss despite increased appetite ```
46
How is Graves disease diagnosed?
Anti TSH receptor antibodies Free T3 and T4 are elevated TSH levels are low Radioactive iodine uptake increased
47
What is the treatment for Graves disease?
Radioactive iodine Anti thyroid drugs Thyroid surgery
48
What are the characteristics of Hashimoto thyroiditis?
TH1 infiltration destroys thyroid gland leading to hypothyroidism Type 4 hypersensitivity
49
How is the presentation of Hashimoto?
``` Hoarseness due to goiter Cold intolerance Bradycardia Constipation, weight gain Decreased sweating ```
50
How is Hashimoto diagnosed?
Elevated TSH level | Antibodies to thyroid peroxidase and thyroglobulin
51
How is Hashimoto treated?
Levothyroxine replacement therapy | Surgery for goiter or malignant nodules
52
What are the characteristics of psoriasis ?
Most common autoimmune disease of the skin Keratinocytes are induced by TH1 and TH17 cytokines Scaly red plaques affecting elbows, knees' scalp, lower back Can also affect eyes and joints
53
How is psoriasis diagnosed?
RF negative Elevated uric acid Sterile pistule fluid with many PMNs Auspitz sign: removal of scales causes small bleeding
54
How to treat psoriasis?
Topical creams Anti inflammatory, biologicals Light therapy Stress reduction
55
What are the characteristics of Rheumatoid Arthritis (RA)?
Destructive disease of the joints Type 4 hypersensitivity Classic signs are morning stiffness, arthritis of 3 or more joints, rheumatoid nodules HLA-DR4 linkage
56
How is RA diagnosed?
ESR and CRP elevated Circulating RF( not pathognomonic) Anti cyclic citrullinated peptide (CCP) antibodies specific ( arg—>citrulline)
57
What is the treatment for RA?
NSAIDs Corticosteroids (prednisone ) Anti TNF alpha: infliximab,adalimumab Soluble TNF receptor: Etanercept/Enbrel
58
What are the characteristics of SLE?
Chronic inflammatory disease that follows a relapsing and remitting course Immune complexes of self DNA are seposited in the skin, kidneys and joints Deficiency in C1,C2 and C4 contributes to development
59
How does SLE present?
Erythema- butterfly rash Glomerulonephritis Arthritis Raynaud phenomenon Bacterial infections are the most common cause of death early on Accelerated arteriosclerosis leading to kidney and heart failure are the most common cause of late mortality
60
How is SLE diagnosed?
Lumpy bumpy pattern on IF Anti dsDNA antibodies correlated with kidney damage and disease severity Anti Smith antibodies detected by Elisa indicate renal involvement
61
How is SLE treated?
Avoid sunlight to prevent flares NSAIDs Steroids Rituximab
62
What are the characteristics of Sjogren syndrome?
Chronic inflammatory disease mediated by CD4+ infiltrate affecting the exocrine glands primarily the lacrimal and salivary
63
How does Sicca syndrome present?
Xerophthalmia Xerostomia with poor oral health Xeroderma, urticaria, purpura Parotid swelling most common sign in children Usually associated with another CT disease ie SLE or RA
64
How is Sicca syndrome diagnosed?
Anti SS-A/Ro Schirmer test for tear production Biopsy suspicious parotid glands and lymph nodes
65
What are the characteristics of GBS?
Ascending paralysis that affects the peripheral nerves Follows infection or vaccination Most important cause of acute flaccid paralysis in countries without polio Lipid antigens of microbes dmonstrate molecular mimicry
66
How is GBS diagnosed?
Elevated CSF protein greater than 0.55g/L without elevated WBCs Abnormal nerve conduction test
67
How is GBS treated?
Treated as medical emergency Closely monitor No corticosteroids- worsen the outcome
68
What are the characteristics of multiple sclerosis?
``` Destruction of myelinated axons in the CNS Primary progressive (PPMS)and relapsing remitting (RRMS) forms Most common neurologic disease of young adults ```
69
How does MS present?
Peak onset 35 Charcot triad: dysarthria, ataxia, tremor Poor judgment Heat makes it worse
70
How is MSdiagnosed?
Plaques of demyelination primarily in the white matter | Abnormal CSF in majority of patients
71
How to treat MS?
Natalizumab prevents entry of leukocytes into CNS Ocrelizumab binds to CD20 useful for PPMS and RRMS Drug to control seizures Regular exercise and physical therapy ABC therapy- reduces relapse frequency and delays disability
72
What are the ABC drugs for MS?
Avonex and Betaserone | Copaxone
73
What is the role of Avonex and Betaserone?
Down regulate expression of B7 and adhesion molecules | Promote TGF beta synthesis
74
What is the role of copaxone?
Induces Treg cells that down regulate inflammatory response