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Immunology Block 2 > Autoimmunity (and Tolerance) > Flashcards

Autoimmunity (and Tolerance) Flashcards

1
Q

what are the 3 types of criteria for “declaring” autoimmune disease?

A

direct proof
indirect proof
circumstantial evidence

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2
Q

direct proof

A

transient disease in newborn due to passive autoimmune antibodies

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3
Q

indirect proof

A

identify target human antigens and reproduce disease in animal model systems

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4
Q

circumstantial evidence

A

statistical demonstration of factors that associate with increased risk; clinical improvement with immunosuppresive therapy

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5
Q

which 3 hypersentivities are associated with autoimmune diseases?

A

Type 2, 3, and 4

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6
Q

which exogenous factors influence expression of autoimmune diseases?

A

hormones
infectious agents
environment

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7
Q

what is the genetics of autoimmune diseases?

A
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8
Q

what are the HLA haplotypes associated with autoimmunity?

A

DQ2, DQ8, DR2, DR3, DR4, DR5, B27

  • linkage disequilibrium?
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9
Q

what is the B27 HLA allotype associated with?

A

Ankylosing spondylitis

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10
Q

Between males and females, which is more susceptible to autoimmune diseases?

A

females

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11
Q

what are the 4 immune privileged sites?

A

brain, eye, uterus (fetus), testes

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12
Q

Autoreactive “Bad” B cells should be eliminated but this is not always the case. But even though they survive, they should not be able to react without ___ cells?

A

T cells

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13
Q

how can you lose immune tolerance?(2)

A
  • self-reactive B and T cells

- dysfunctional negative selection gives rise to autoimmune diseases

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14
Q

How does self-reactive B and T cells lead to immune tolerance?

A
  • T cells reacting strongly to self fail to be eliminated

- B cells recognizing autoantigens exist in circulation

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15
Q

what are the ways that dysfucntional negative selection give rise to autoimmune diseases?(4)

A

1- defect in the AIRE gene
2- APECED and APD
- Finns, Sardinians, Iranian Jews
- patients also suffer from candiasis-ectodermal dystrophy

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16
Q

APECED or APD caused by?

A

a defect in the AIRE gene

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17
Q

what are APECED or APD?

A

two diverse groups of autoimmune diseases caused by defect in AIRE gene

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18
Q

what are two examples of diseases that people with APECED suffer?

A
  • alopecia

- vitiligo

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19
Q

what occurs in the loss or lack of peripheral tolerance?

A

soluble CTLA-4 binds B7 preventing CD28 interactions

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20
Q

what are the 2 molecules that bind T cell activation?

A
  • normally CD28

- CTLA-4

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21
Q

what does CTLA-4 do?

A

dampens T cell activation by competing with CD28 for B7

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22
Q

Patients with which diseases have an increased expression of CTLA-4?(3)

A

Graves
Hashimoto
IDDM

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23
Q

which cytokines are responsible for CD4 cell regulation?

A

IL4
IL10
TGF -beta

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24
Q

what is the transcriptional repressor expressed by CD4+ T regs?

A

FoxP3

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25
Q

how does cross reacting antigens or molecular mimicry allow for controls to be bypassed?

A
  • provide help for B cells to produce antibodies

- microbial antigens share amino acid sequences wth mamalian proteins

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26
Q

revisit effector mechanisms

A

…

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27
Q

what are some consequences of cross reacting microbes associated with autoimmunity?

A
  • strep = rheumatic fever
  • chlamydia = arthritis
  • shigella = reactive arthritis
  • Borrelia burgdorferi = chronic arthritis in Lyme disease
  • Coxsackie = Type 1 diabetes
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28
Q

Reiter’s syndrome and Reactive arthritis

A
  • both autoimmune infections linked to infections
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29
Q

Reiter’s syndrome causes

A
  • genital infection with chlamydia trachomatis or gastroenteritis caused by enteric pathogens (Yersinia enerocolitica)
  • form or arthritis similar to ankylosis spondylitis
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30
Q

Reactive Arthritis causes

A
  • a number of pathogens that cause gastrointestinal infection from food poisoning are implicated
31
Q

possible mechanisms of induction of autoimmunity (3)

A
  • chemical modification of antigen
  • polyclonal activation
  • viral factors
  • abnormal expression of MHC 2
  • deficiency in complement components
  • breach of central tolerance
  • loss of peripheral tolerance
32
Q

Type 2 Hypersensitivity and autoimmunity

A

autoimmune diseases caused by antibodies against a cell surface or tissue marker

33
Q

Type 2 autoimmunity list

A 
1- Autoimmune Hemolytic Anemia
2- Autoimmune thrombocytopenia purpura
3- Goodpasture's syndrome
4- Pemphigus vulgaris
5- Pemphigus foliaceus
6- Acute rheumatic fever
7- Graves disease
8- Myasthenia Gravis
AA-GPP-AGM
34
Q

Type 2- Autoimmune hemolytic anemia

A
  • warm antibodies (some IgG against antigen) initiate immune adherence and phagocytosis (identified by direct Coombs test)
  • cold antibodies- IgM binds to I or I antigens on glyphorin RBC ( activates complement and hemolysis occurs when patients are exposed to cold)
35
Q

Type 2- autoimmune thrombocytopenia purpura

A
  • anti platelets antibodies

- accelerated removal by phagocytes in spleen and liver

36
Q

Type 2 -Goodpasture’s syndrome

A
  • antibodies against the alpha-3 chain of type 4 collagen found in the basement membrane of kidney and lung
  • LINEAR pattern of immunofluorescence
37
Q

Type 2- Pemphigus vulgaris

A
  • blisters and rash caused by antibodies against epithelium

- desmogleins: adhesion molecules in the desmosomes that bind keratinocytes together

38
Q

Type 2- Pemphigus foliaceus

A

…

39
Q

Type 2- acute rheumatic fever

A
  • antibodies against Streptoccal M proteins that cross react with myocardium (anti-myosin and sarcolemmal proteins)
40
Q

Type 2 - Graves disease

A
  • abnormal class 2 expression by thyroid cells
  • IgG against TSH receptors leading to hypersensitivity
  • transient Grave’s disease in newborns
41
Q

Type 2- Myasthenia Gravis

A
  • anti-acetylcholine receptor antibodies
  • block Ach binding to neuromuscular junctions
  • muscle weakness: ptosis, swallowing, breathing
  • thymoma
42
Q

pernicious anemia? Type 2?

A
  • antibodies to intrinsic factor
  • antiparallel cell antibodies
  • no vitamin B12 uptake
43
Q

Type 3 HyperSensitivity and Autoimmunity

A

Autoimmune diseases caused by immune complex deposition

44
Q

Type 3 HyperSensitivity and Autoimmunity List

A

1- Subacute bacterial endocarditis
2- Mixed essential cryoglobulinemia
3- Systemic lupus erythematosus

45
Q

Subacute bacterial endocarditis

A
  • autoantigen: bacterial antigen

- consequence: causes Glomerulonephritis

46
Q

Mixed essential cryoglobulinemia

A
  • autoantigen: Rheumatoid factor IgG complexes (with or without hepatitis C antigens)
  • consequence: Systemic vasculitis
47
Q

Systemic lupus erythematosus

A
  • autoantigen: DNA, histones, ribosomes, snRNP, scRNP

- consequence: Glomerulonephritis, vasculitis, arthritis

48
Q

what type of sensitivity is rheumatoid arthritis?

A

Type 4

49
Q

in SLE, what class of antibodies against ds DNA correlate best with the disease?

A

IgG

50
Q

In SLE Aside from antibodies against ds DNA, what targets exist?

A
  • ss denatured DNA
  • nucleus
  • histone
  • RNP and Sm proteins
51
Q

In SLE, which toll like receptor recognizes unmethylated CpG nucleotide sequences found on bacterial DNA but also human DNA?

A

TLR-9

52
Q

In SLE, what is the second signal generated via?

A

NFkB

53
Q

what type of test is used to test for SLE?

A
  • anti-nuclear antibodies

- patient serum is reacted with rat liver cells

54
Q

How is the anti-nuclear antibody reaction detected?

A
  • with FITC- conjugated anti-human Ig antibodies

- POSITIVE TEST - fluorescent nucleus

55
Q

the butterfly rash present in SLE is similar in appearance to patients with ____

A

serum sickness

immune complex deposition in the skin

56
Q

what is the pattern of fluorescence in SLE?

A

LUMPY BUMPY

- immune complexes deposit on kidney, activate C, PMNs

57
Q

what pathologies are caused by SLE?

A

glomerulonephritis
proteinuria
hematuria

58
Q

Type 4 Hypersensitivity & Autoimmunity

A

T-cell mediated diseases

59
Q

Type 4 Hypersensitivity & Autoimmunity List

A 
1- multiple sclerosis
2- IDDM -insulin dependent diabetes mellitis
3- Hashimoto thyroiditis
4- Rheumatoid arthritis
5- Celiac disease
6- Sjogren's Syndrome?
60
Q

Multiple sclerosis

A

demyelination of CNS and sclerotic plaque replacement leading to relapsing or chronic progressive paralytic course
- evidence of link to viral infection due to antigenic mimicry

61
Q

Multiple sclerosis mechanism

A

1- TH1 secreting IFNgamma together with macrophages penetrate the blood-brain barrier
2- Macrophages then secrete proteases and cytokines induce inflammation along the myelin sheath (leads to loss of myelin and sclerotic plaques)
- Fas induction - apoptosis of neuronal cells

62
Q

What experimental model has been used as evidence that MS is autoimmune?

A

EAE - Experimental Allergic Encephalitis

- inject myelin basic protein (MBP) into mice with adjuvant induces MS symptoms

63
Q

IDDM

A

chronic inflammatory destruction of the insulin producing b-islet cells of the pancreas

64
Q

IDDM

A

…

65
Q

IDDM

A

…

66
Q

Hashimoto Thyroiditis

A

…

67
Q

Hashimoto Thyroiditis

A

…

68
Q

Rheumatoid Arthritis

A

…

69
Q

Rheumatoid Arthritis

A

hypersenitivity to food that has much in common with autoimmune disease)

70
Q

Rheumatoid Arthritis

A

…

71
Q

Celiac Disease

A

…

72
Q

Celiac Disease

A

…

73
Q

Celiac Disease

A

…

74
Q

Sjogren’s Syndrome

A

…

Immunology Block 2 (12 decks)

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