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GBA Immunology > Week 12 - Autoimmunity and Tolerance > Flashcards

Week 12 - Autoimmunity and Tolerance Flashcards

1
Q

Natural Autoimmunity (Good autoimmunity)

A

B1 cells (CD5+) produce polyreactive, low affinity binder IgM natural autoantibodies that recognize conserved molecules.

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2
Q

Heat Shock Proteins, Enzymes (CyteC), Membrane Proteins (Beta2m), Cytoplasmic Proteins (Actin), DNA, IL1, Albumin, IgG.

These are all examples for shared ______ of Human and Microbes that are possibly recognized by _______ ________.

A

These are all examples for shared Antigens of Human and Microbes that are possibly recognized by Natural Autoimmunity.

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3
Q

Natural Autoimmunity is apart of the process of the development of ______ since over time the reaction gets less and less _______ with the exposure.

A

Natural Autoimmunity is apart of the process of the development of Tolerance since over time the reaction gets less and less powerful with the exposure.

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4
Q

Pathological autoimmunity develops if the

immune _______ is broken or insufficient.

A

Pathological autoimmunity develops if the

immune tolerance is broken or insufficient.

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5
Q

Immune tolerance which is unresponsiveness to a given antigen could be either :

A

Peripheral or Central

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6
Q

T cells that recognize self peptide MHC
complexes with high avidity, undergo
clonal deletion (apoptosis) in a process called _______ ______ this is part of the ______ _________

A

T cells that recognize self peptide MHC
complexes with high avidity, undergo
clonal deletion (apoptosis) in a process called Negative Selection this is part of the Central Tolerance.

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7
Q

In Negative Selection, T cells with weak or intermediate TCR avidity get to the ________ .

A

In Negative Selection, T cells with weak or intermediate TCR avidity get to the periphery.

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8
Q

Peripheral tolerance mechanisms:

Anergy

A

Inability to respond to stimuli in the absence of costimulation

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9
Q

Peripheral tolerance mechanisms:

Ignorance

A

low avidity TCR binding

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10
Q

Peripheral tolerance mechanisms:

Antigen Segregation - Immunoprivileged sites

A

Brain, Testis, Thyroid, Pregnant Uterus (In general no Lymphatic drainage)
For example BBB is the segregating entity of the Brain

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11
Q

Peripheral tolerance mechanisms:

Antigen Segregation - Molecules Involved in its sites

A
  • Immunosuppressive cytokines e.g. TGF-Beta , IL 10

- FasL expressed by Cells allow for Avoidance from T cell

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12
Q

Release of hidden (cryptic) antigens from immune privileged sites - Give an example and What could be the consequence.

A

Injury of the eye causes the release of its protein antigens to the Blood and eventually lymphatic system.
Possible attack on Eye tissues by T cells can happen.

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13
Q

Peripheral tolerance mechanisms:

Cytokine Devations, by Helminths Response, Allergy or cell mediated Immune response could (3 Examples) -

A

Damage immune tolerance and lead to:

Rheumatoid Arthritis, Crohn’s or Multiple Sclerosis

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14
Q

Peripheral tolerance mechanisms:

Regulatory T cells - CTLA4

A

Aka CD152 , is a protein receptor that acts as an “off” switch when bound to CD80 or CD86 on the surface of antigen-presenting cells.

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15
Q

Peripheral tolerance mechanisms:

Regulatory T cells - PD-1

A

Programed Cell Death Protein-1 (CD279) - Promotes apoptosis in antigen-specific T-cells in lymph nodes and reduces apoptosis in regulatory T cells.

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16
Q

Peripheral tolerance mechanisms:

Regulatory T cells and TH3 cells- FOX3P

A

Master regulator transcription factor upregulating regulatory T-cell function, and may inhibit transcription of key genes following stimulation of T cell receptors.

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17
Q

Peripheral tolerance mechanisms:

Regulatory T cells - Cytokines Released

A

IL-10 and TGF-beta (immunosuppressive)

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18
Q

Peripheral tolerance mechanisms:

TH3 cells - Cytokines Released

A

IL-10 and TGF-beta (immunosuppressive)

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19
Q

Peripheral tolerance mechanisms:

Tr1 cells - Cytokines Released

A

IL 10 (immunosuppressive)

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20
Q

Peripheral tolerance mechanisms:

Clonal exhaustion

A

Activation induced T cell death (AICD),

apoptosis is mediated by Fas FasL interaction.

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21
Q

Autoimmune diseases - 6 General Principles for all of them

MB5UFC

A
  1. Multifactorial: Polygenic +Environmental factors
  2. B cell , T cell , immune complex mediated
  3. 5% of the adult population
  4. Usually in adulthood
  5. Frequent in women
  6. Characterized by Exacerbations and Remissions
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22
Q

Genes determining autoimmune disease susceptibility

A

MHC, AIRE, FAS, PD, CTLA4, Inhibitory Fc receptors

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23
Q

Cross reactivity (molecular mimicri)

A

Viral and bacterial peptides might mimic self peptides causing Autoimmunity

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24
Q

Bacterial Example for Molecular Mimicry

A

Streptococcal antigens → similar to endocardial antigens → inflammation , valve deformity → Rheumatic fever.

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25
Q

Viral Examples for Molecular Mimicry:

Poliovirus - Protein in virus and What is mimicked

A

Poliovirus

VP2 - ACh receptor

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26
Q

Viral Examples for Molecular Mimicry:

HIV - Protein in virus and What is mimicked

A

HIV

p24 - IgG Constant Region

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27
Q

Viral Examples for Molecular Mimicry:

Measles - Protein in virus and What is mimicked

A

Measles

p3 - Myelin Basic Protein

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28
Q

__________ (e.g. bacterial toxins) bind the MHC II molecules and the T cell receptors from the outside, thus, a high number of T cell clones can be activated in a ___ _______ way.

A

Superantigens (e.g. bacterial toxins) bind the MHC II molecules and the T cell receptors from the outside, thus, a high number of T cell clones can be activated in a non specific way.

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29
Q

Autoimmune Diseases Associated with Brain: (3 examples)

A

Multiple Sclerosis
Guillain Barre Syndrome
Autism

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30
Q

Autoimmune Diseases Associated with Thyroid: (3 examples)

A

Thyroiditis
Hashimoto’s Disease
Graves’s Disease

31
Q

Autoimmune Diseases Associated with GI: (3 examples)

A

Celiac’s, Crohn’s, UC, T1DM

32
Q

Autoimmune Diseases Associated with Blood: (3 examples)

A

Leukemia, SLE, Hemolytic Dysglycemia

33
Q

Autoimmune Diseases Associated with Lungs: (3 examples)

A

Fibromyalgia

Wegener’s Granulomatosis

34
Q

Autoimmune Diseases Associated with Bone: (3 examples)

A

Spondylarthritis ankylopoetica
RA
Polymyalgia Rheumatica

35
Q

B1 cells (CD_+) produce polyreactive, low affinity binder IgM natural ____________ that recognize conserved molecules.

A

B1 cells (CD5+) produce polyreactive, low affinity binder IgM natural autoantibodies that recognize conserved molecules.

36
Q

The natural autoantibodies are arranged in a network of hierarchy for binding : from antigen up to the most conserved antibody. How is this network called?

A

idiotype/anti-idiotype network

37
Q

What transcription factor allows the promiscuous gene expression of tissue antigens in the thymus?

A

Autoimmune Regulator (AIRE)

38
Q

5 most important autoantibodies in autoimmune disorders:

1) ___
2) ANCA
3) Anti-phospholipid antibodies
4) Rheuma factor
5) ACPA

A

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) Anti-phospholipid antibodies
4) Rheuma factor
5) ACPA

39
Q

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ____
3) APS: Antiphospholipid antibodies
4) Rheuma factor
5) ACPA

A

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) APS: Antiphospholipid antibodies
4) Rheuma factor
5) ACPA

40
Q

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) ___
4) Rheuma factor
5) ACPA

A

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) APS: Antiphospholipid antibodies
4) Rheuma factor
5) ACPA

41
Q

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) APS: Antiphospholipid antibodies
4) _________ ______
5) ACPA

A

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) APS: Antiphospholipid antibodies
4) Rheuma factor
5) ACPA

42
Q

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) APS: Antiphospholipid antibodies
4) Rheuma factor
5) ____

A

5 most important autoantibodies in autoimmune disorders:

1) ANA
2) ANCA
3) APS: Antiphospholipid antibodies
4) Rheuma factor
5) ACPA

43
Q 
Methods for the determination of autoantibodies:
\_\_
ELISA
CIE=counterimmunoelectrophoresis
Multiplex assays
A 
Methods for the determination of autoantibodies:
IF
ELISA
CIE=counterimmunoelectrophoresis
Multiplex assays
44
Q 
Methods for the determination of autoantibodies:
IF
\_\_\_\_\_
CIE=counterimmunoelectrophoresis
Multiplex assays
A 
Methods for the determination of autoantibodies:
IF
ELISA
CIE=counterimmunoelectrophoresis
Multiplex assays
45
Q 
Methods for the determination of autoantibodies:
IF
ELISA
\_\_\_
Multiplex assays
A 
Methods for the determination of autoantibodies:
IF
ELISA
CIE=counterimmunoelectrophoresis
Multiplex assays
46
Q 
Methods for the determination of autoantibodies:
IF
ELISA
CIE=counterimmunoelectrophoresis
\_\_\_\_\_\_\_ \_\_\_\_\_
A 
Methods for the determination of autoantibodies:
IF
ELISA
CIE=counterimmunoelectrophoresis
Multiplex assays
47
Q

ANA

A

Anti-Nuclear Autoantibodies: autoantibodies that bind to contents of the cell nucleus.
antigen: double stranded DNA, histone, topoisomerase, RNP, Centromere (Cenp‐B)

48
Q

Anti-CCP/ACPA

A

Anti-cyclic Citrullinated Protein Antibody

49
Q

APS

A

Antiphospholipid syndrome antibody panel -

antigens: cell membrane proteins and proteins involved in blood coagulation

50
Q

RF

A

Rheuma factor: Antibody against the Fc fragment of IgG

51
Q

ANCA

A

Anti-neutrophil cytoplasmic antibodies
P-ANCA: Perinuclear (Strong Cations)
C-ANCA: Cytoplasmic (Weak Cations)

52
Q 
The most important Targets of APS Autoantibodies: 
Cardiolipin
Phosphatidylserine
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Prothrombin
Lupus anticoagulant (LA)
A 
The most important Targets of APS Autoantibodies: 
Cardiolipin
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
53
Q 
The most important Targets of APS Autoantibodies: 
Cardiolipin 
Phosphatidylserine
β-2-glycoprotein I 
\_\_\_\_\_\_\_\_
Lupus anticoagulant (LA)
A 
The most important Targets of APS Autoantibodies: 
Cardiolipin
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
54
Q 
The most important Targets of APS Autoantibodies: 
Cardiolipin
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
\_\_\_\_\_\_\_\_\_\_
A 
The most important Targets of APS Autoantibodies: 
Cardiolipin 
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
55
Q 
The most important Targets of APS Autoantibodies: 
Cardiolipin 
\_\_\_\_\_\_\_\_\_\_\_\_
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
A 
The most important Targets of APS Autoantibodies: 
Cardiolipin 
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
56
Q 
The most important Targets of APS Autoantibodies: 
\_\_\_\_\_\_\_\_ 
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
A 
The most important Targets of APS Autoantibodies: 
Cardiolipin
Phosphatidylserine
β-2-glycoprotein I 
Prothrombin
Lupus anticoagulant (LA)
57
Q

What is the testing methods for APS?

A

ELISA or Functional Testing

58
Q

RA: about 80% sensitivity of patients show sensitivity to:

59
Q

RA-specific antibody, which is more specific than RF.
Often positive in the early (non-specific) stage of RA. Part of the new RA classification criterion. Positivity is a poor prognostic factor.

A

Anti-cyclic citrullinated protein (anti-CCP)

60
Q

Antimitochondrial antibodies (AMA) - What diseases?

A

Primary biliary cirrhosis (PBC), but rarely it may also be positive in other autoimmune hepatitis

61
Q

Anti-smooth muscle (F-actin) antibody (SMA) - What diseases?

A

positive in autoimmune hepatitis, but it can also be positive in many other liver diseases

62
Q

Anti-microsomal antibody (LKM-1) - What diseases?

A

antibody against cytochrome P450 2D6 protein – characteristic to type 2. autoimmune hepatitis

63
Q

Liver specific proteins (LSP) - What diseases?

A

characteristic to type 2. autoimmune hepatitis

64
Q

Symptomes are„butterfly” erythema, Pleuritis, Nephritis, Joint pain, Cardial complaints, Neurological symptoms
with ANA+
What could be the diagnosis?

65
Q

Muscle weakness, diplopia, swallowing difficulty (dysphagia) with Anti-AChR+.
What could be the diagnosis?

A

Myasthenia Gravis

66
Q

Dryness of the eyes and mouth
with Anti-SSA+ and Anti-SSB+
What could be the diagnosis?

A

Sjögren’s syndrome

67
Q

Rigid, swollen, painful joints especially in the morning
with ANA+, RF+ positivity, Anti-CCP+
What could be the diagnosis?

A

Rheumatoid arthritis

68
Q

What is the role of Anti-dsDNA in SLE?

A

Predictive Marker

69
Q

What is the role of Anti-Sm/RNP/Rho/La in SLE?

70
Q

What are the changes that occur in C3,C4 and CH50 while therapy for SLE is taking place?

A

Exacerbation at first, ease and finally ascending

71
Q

Citrullination: Enzyme

A

Peptidyl-arginine deiminase (PAD) enzymes (post transcriptionally)

72
Q

Peptides may undergo Citrullination:

A

fibrin, vimentine, enolase

73
Q

90% of the Caucasian patients are HLA B27 positive in which autoimmune disease?

A

Bechterew’s disease (ankylosing spondylitis)

GBA Immunology (15 decks)

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