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Immuno Final > 6 Autoimmunity > Flashcards

6 Autoimmunity Flashcards

1
Q

what percentage of the world suffers from autoimmune diseases?

A

> 5%

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2
Q

T/F any organ can be affected by autoimmunity?

A

True

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3
Q

What are the 3 ways that the immune system can cause disease?

A

1) reactions against microbes (too much)
2) reactions against antigens (too much)
3) Autoimmunity (reactivity to self)

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4
Q

What is autoimmunity?

A

the failure of tolerance to self antigens which can occur at any of the steps of central and peripheral tolerance.

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5
Q

where does central tolerance occur? peripheral tolerance?

A

central tolerance happens in the thymus and bone marrow.

Peripheral tolerance occurs in the peripheral tissues.

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6
Q

What are autoantigens?

A

antigens that activate autoimmune responses

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7
Q

what are autoantibodies?

A

antibodies generated by autoimmune responses

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8
Q

which type of hypersensitivity reactions are responsible for autoimmune diseases?

A

Type 2,3,4 but not type 1

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9
Q

T/F Most autoimmune diseases involve both T and B cells?

A

true

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10
Q

Autoimmune diseases are described as chronic, progressive, and self perpetuating. Epitope spreading is also involved which is what?

A

a response initiated against self antigen that injures self tissue, and the injured tissue releases alterations of other tissue antigens that activate the immune system even more.

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11
Q

T/F one of the problems with autoimmune diseases is that there is a constant supply of autoantigens that are not easily cleared from the body?

A

true. During a normal immune response the antigens are cleared.

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12
Q

T/F Autoimmune diseases are generally caused by a change in one immunological polymorphism?

A

False, there are generally multiple genetic polymorphisms that contribute in autoimmune diseases.

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13
Q

Autoimmune diseases have a strong genetic component. About _________% of monzygotic twins and ________% of dizygotic twins have concordance in diabetes Mellitus type 1?

A

35-50% of monozygotic

5% of dizygotic

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14
Q

The strongest genetic associations with autoimmune disease are with what?

A

MHC genes

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15
Q

Genes predisposing autoimmunity include the following functions?

A

1) auto-antigen clearance
2) T reg cell function
3) Apoptosis
4) signaling
5) cytokine gene expression

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16
Q

Very few autoimmune diseases are caused by single gene defects, but 3 specifically are, which include?

A

1) AIRE
2) FOXP3
3) FAS

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17
Q

What happens with an AIRE gene knockout?

A

decreased expression of self antigens in thymus resulting in defective negative selection of self reactive T cells. (TF knockout)

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18
Q

What disease does AIRE cause? (2 names for the same thing)

A

1) APECED (autoimmune poly endocrinopathy candidiasis ectodermal dystrophy)
2) APS1 (autoimmune polyglandular syndrome 1)

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19
Q

What conditions are seen with APECED, aka APS 1?

A

hypoparathyroidism
adrenal insufficiency
hypogonadism

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20
Q

What happens with a FOXP3 knockout?

A

you get the disease IPEX

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21
Q

what causes IPEX (FOXP3 gene knockout)?

A

It is caused by decreased function of CD4 and CD25 T reg cells. (TF knockout)

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22
Q

what are some diseases that result form FOXP3 gene knockout? What happens to these patients?

A 
Neonatal Diabetes type 1
thyroiditis
chronic diarrhea
dermatitis
(it is usually fatal within the first year of life)
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23
Q

What happens when there is a FAS gene knockout?

A

You get the disease ALPS that is caused by failure of apoptotic death of self reactive B and T cells.

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24
Q

what does ALPS stand for?

A

autoimmune lympho proliferative syndrome

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25
Q

If you have ALPS, which diseases specifically fit into this category?

A

glomerulonephritis
hemolytic anemia
Hepatomegaly

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26
Q

T/F bacterial and viral infections can contribute to the development and exacerbation of autoimmunity?

A

true

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27
Q

what is bystander activation?

A

when infections induce local innate immune responses in tissue that recruit leukocytes and result in activation of tissue APC’s. These APC’s activate bystander T cells that are not specific to the antigen and result in breakdown of tolerance leading to tissue damage.

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28
Q

What is molecular mimicry?

A

Microbes can contain antigens that are very similar to self antigens, but when immune system detects and kills antigen, it also tries to kill areas of self that are very similar to the bacterial antigen. Ex: Rheumatic fever with Streptococcus and heart valves.

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29
Q

how do you classify autoimmune diseases?

A

1) organ specific
2) systemic
3) Hypersensitivity reaction type that causes the injury.

30
Q

Hashimoto Thyroiditis is what type of autoimmune disease?

A

Organ specific autoimmune disease with the antibody against thyroid paroxidase.

31
Q

What type of autoimmune disease is Graves’ Disease?

A

An organ specific autoimmune disease with the antibody against TSH receptor.

32
Q

How would you classify SLE (Lupus)?

A

It’s a systemic autoimmune disease with antibody against nuclear chromatin.

33
Q

How would you classify Type I Diabetes?

A

Organ specific autoimmune disease against pancreatic beta cells.

34
Q

How would you classify Rheumatoid Arthritis?

A

Systemic autoimmune disease.

35
Q

What is the prevalence of SLE? Who does is affect most? At what age does it usually begin?

A

1) 20-150 cases per 100,000
2) 10 times more prevalent in female.
3) 15-55 years of age.

36
Q

About how many loci predispose you to SLE?

A

50 gene loci, many of which target the compliment cascade.

37
Q

What is the major problem found with SLE?

A

Immune complex deposition in every organ. Ex: Glomerulonephritis, Arthritis.

38
Q

There are two important antibodies in SLE, which are?

A

1) ANA (Anti Nuclear Ab)

2) Anti ds DNA

39
Q

What is important about ANA?

A

ANA is very sensitive for SLE, but not specific. (negative ANA essentially excludes SLE)

40
Q

What is important about anti ds DNA?

A

It is very specific for SLE. (Its level correlates with Nephritis and activity of the disease)

41
Q

Clinical features of SLE include

A 
Rash
Arthritis
Glomerulonephritis
Vasculitis
Endocarditis
Hemolytic Anemia
CNS involvement
42
Q

How do you treat SLE?

A

Immunosuppressive medications

43
Q

There are 11 criteria for diagnosing SLE, how many are required to make a correct diagnosis of SLE?

A

4 or more out of the 11.

44
Q

what is the most common inflammatory arthritis?

A

rheumatoid arthritis at 1% of the population.

45
Q

what are 2 major risk factors for RA?

A

HLA-DR4 mutation, and cigarette smoking

46
Q

T/F T cell and antibodies both contribute to joint inflammation in RA?

A

true

47
Q

Citrulline peptides are a major factor in RA. Where do they come from?

A

enzymatic conversion of arginine to citrulline.

48
Q

synovial inflammation is perpetuated by cytokines including?

A

IL-17
TNF
IL-1

49
Q

What are some clinical features of RA?

A

destruction of bone and cartilage
disability in 10-20 years of onset
inflammation in nearly all joints

50
Q

what is rheumatoid factor?

A

A test for Rheumatoid arthritis. It tests the circulating IgM antibodies against the Fc portion of the patients own IgG’s.

51
Q

besides testing for rheumatoid factor what is another way of testing for rheumatoid arthritis?

A

by checking for antibodies against citrullinated peptides. (anti CCP)

52
Q

what are two treatments for RA?

A

glucocorticoids

DMARD (disease modifying anti rheumatic drugs)

53
Q

T/F active medications for RA include drugs that inhibit TNF alpha, IL-1, and IL-6 of the macrophage?

A

true

54
Q

What causes diabetes mellitus 1?

A

impaired insulin production through destruction of the pancreatic beta cells. There are often antibodies to the islet cells and there is a strong correlation with HLA-DR3 and DR4.

55
Q

what percentage of the population has DM type 1?

A

.2%

56
Q

when does diabetes 1 usually show up?

A

4-6 years and 10-14 years of age.

2/3 of all cases are diagnoses inpatients under 19

57
Q

what are some clinical features of diabetes mellitus type 1?

A

1) hyperglycemia
2) ketoacidosis
3) Macro-vascular problems: atherosclerosis/ischemic necrosis
4) Micorvascular problems: damage to retina, kidney, nerves

58
Q

what is the most common disorder of neuromuscular transmission?

A

Myasthenia gravis

59
Q

what is the cause of myasthenia gravis?

A

antibodies against the acetycholine receptor that block its function at the motor end plate.

60
Q

T/F myasthenia gravis is associated with thymoma’s?

A

true. 60-70% with MG have thymic hyperplasia, and 10-15% have thymoma.

61
Q

what is a thymoma?

A

a tumor of the thymus gland

62
Q

what are some clinical features of myasthenia gravis?

A

muscle weakness
double vision
respiratory weakness that is called myasthenic crisis.

63
Q

How do you treat myasthenia gravis?

A

anticholinesterases
immunosupression
Thymectomy

64
Q

What is graves disease and what causes it?

A

hyperthyroidism that is caused by autoantibodies to the TSH receptor which activates them. 7 times more likely in females.

65
Q

where do you find the TSH receptor?

A

Thyroid, but also….
adipocytes
fibroblasts
bone cells

66
Q

what are some clinical features of graves disease?

A 
anxiety
tremors
heat intolerance
weight loss
proptosis (bulging eyes)
67
Q

how do you treat graves disease?

A

1) antithyroid drugs
2) radioactive iodine
3) thyroidectomy

68
Q

What is Hashimotos thyroiditis?

A

the most common cause of hypothyroidism in the USA

It affects women 7 x more than men, and it is an autoimmune disease(auto antibodies) that destroys the thyroid gland.

69
Q

what are some symptoms of Hashimotos thyroiditis?

A 
fatigue
goiter
cold intolerance
weight gain
depression
70
Q

how do you treat hashimotos disease?

A

thyroxine or T4 replacement

71
Q

what is another name for hashimotos thyroiditis?

A

chronic autoimmune thyroiditis

Immuno Final (7 decks)

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