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Immunology Block 2 > Autoimmunity (and Tolerance) > Flashcards

Autoimmunity (and Tolerance) Flashcards

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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
how does cross reacting antigens or molecular mimicry allow for controls to be bypassed?
- provide help for B cells to produce antibodies | - microbial antigens share amino acid sequences wth mamalian proteins
26
revisit effector mechanisms
...
27
what are some consequences of cross reacting microbes associated with autoimmunity?
- strep = rheumatic fever - chlamydia = arthritis - shigella = reactive arthritis - Borrelia burgdorferi = chronic arthritis in Lyme disease - Coxsackie = Type 1 diabetes
28
Reiter's syndrome and Reactive arthritis
- both autoimmune infections linked to infections
29
Reiter's syndrome causes
- genital infection with chlamydia trachomatis or gastroenteritis caused by enteric pathogens (Yersinia enerocolitica) - form or arthritis similar to ankylosis spondylitis
30
Reactive Arthritis causes
- a number of pathogens that cause gastrointestinal infection from food poisoning are implicated
31
possible mechanisms of induction of autoimmunity (3)
- 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
Type 2 Hypersensitivity and autoimmunity
autoimmune diseases caused by antibodies against a cell surface or tissue marker
33
Type 2 autoimmunity list
``` 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
Type 2- Autoimmune hemolytic anemia
- 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
Type 2- autoimmune thrombocytopenia purpura
- anti platelets antibodies | - accelerated removal by phagocytes in spleen and liver
36
Type 2 -Goodpasture's syndrome
- antibodies against the alpha-3 chain of type 4 collagen found in the basement membrane of kidney and lung - LINEAR pattern of immunofluorescence
37
Type 2- Pemphigus vulgaris
- blisters and rash caused by antibodies against epithelium | - desmogleins: adhesion molecules in the desmosomes that bind keratinocytes together
38
Type 2- Pemphigus foliaceus
...
39
Type 2- acute rheumatic fever
- antibodies against Streptoccal M proteins that cross react with myocardium (anti-myosin and sarcolemmal proteins)
40
Type 2 - Graves disease
- abnormal class 2 expression by thyroid cells - IgG against TSH receptors leading to hypersensitivity - transient Grave's disease in newborns
41
Type 2- Myasthenia Gravis
- anti-acetylcholine receptor antibodies - block Ach binding to neuromuscular junctions - muscle weakness: ptosis, swallowing, breathing - thymoma
42
pernicious anemia? Type 2?
- antibodies to intrinsic factor - antiparallel cell antibodies - no vitamin B12 uptake
43
Type 3 HyperSensitivity and Autoimmunity
Autoimmune diseases caused by immune complex deposition
44
Type 3 HyperSensitivity and Autoimmunity List
1- Subacute bacterial endocarditis 2- Mixed essential cryoglobulinemia 3- Systemic lupus erythematosus
45
Subacute bacterial endocarditis
- autoantigen: bacterial antigen | - consequence: causes Glomerulonephritis
46
Mixed essential cryoglobulinemia
- autoantigen: Rheumatoid factor IgG complexes (with or without hepatitis C antigens) - consequence: Systemic vasculitis
47
Systemic lupus erythematosus
- autoantigen: DNA, histones, ribosomes, snRNP, scRNP | - consequence: Glomerulonephritis, vasculitis, arthritis
48
what type of sensitivity is rheumatoid arthritis?
Type 4
49
in SLE, what class of antibodies against ds DNA correlate best with the disease?
IgG
50
In SLE Aside from antibodies against ds DNA, what targets exist?
- ss denatured DNA - nucleus - histone - RNP and Sm proteins
51
In SLE, which toll like receptor recognizes unmethylated CpG nucleotide sequences found on bacterial DNA but also human DNA?
TLR-9
52
In SLE, what is the second signal generated via?
NFkB
53
what type of test is used to test for SLE?
- anti-nuclear antibodies | - patient serum is reacted with rat liver cells
54
How is the anti-nuclear antibody reaction detected?
- with FITC- conjugated anti-human Ig antibodies | - POSITIVE TEST - fluorescent nucleus
55
the butterfly rash present in SLE is similar in appearance to patients with ____
serum sickness | immune complex deposition in the skin
56
what is the pattern of fluorescence in SLE?
LUMPY BUMPY | - immune complexes deposit on kidney, activate C, PMNs
57
what pathologies are caused by SLE?
glomerulonephritis proteinuria hematuria
58
Type 4 Hypersensitivity & Autoimmunity
T-cell mediated diseases
59
Type 4 Hypersensitivity & Autoimmunity List
``` 1- multiple sclerosis 2- IDDM -insulin dependent diabetes mellitis 3- Hashimoto thyroiditis 4- Rheumatoid arthritis 5- Celiac disease 6- Sjogren's Syndrome? ```
60
Multiple sclerosis
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
Multiple sclerosis mechanism
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
What experimental model has been used as evidence that MS is autoimmune?
EAE - Experimental Allergic Encephalitis | - inject myelin basic protein (MBP) into mice with adjuvant induces MS symptoms
63
IDDM
chronic inflammatory destruction of the insulin producing b-islet cells of the pancreas
64
IDDM
...
65
IDDM
...
66
Hashimoto Thyroiditis
...
67
Hashimoto Thyroiditis
...
68
Rheumatoid Arthritis
...
69
Rheumatoid Arthritis
hypersenitivity to food that has much in common with autoimmune disease)
70
Rheumatoid Arthritis
...
71
Celiac Disease
...
72
Celiac Disease
...
73
Celiac Disease
...
74
Sjogren's Syndrome
...

Immunology Block 2 (12 decks)

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