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MI and Genomics > MI 05a: Tolerance and Autoimmunity > Flashcards

MI 05a: Tolerance and Autoimmunity Flashcards

1
Q

Immunological tolerance is ability of immune system to (X), thus becoming (responsive/unresponsive) to (Y).

A

X = recognize self from non-self;
Unresponsive
Y = self antigens

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2
Q

Central tolerance develops in (central/peripheral) lymph organs. Potential outcomes of recognizing (X) are:

A

Central;
X = self-antigen

  1. Apoptosis
  2. Treg development
  3. B cell receptor editing
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3
Q

Tregs are just specialized (X) cells. Which molecules/receptors characterize Tregs?

A

X = CD4 T cells

  1. CD25 (alpha chain of IL-2)
  2. FoxP3 (transcription factor)
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4
Q

After maturation (inside/outside) thymus, Tregs function to (activate/suppress) (X) cells.

A

Outside;
Suppress

X = lymphocytes and APCs

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5
Q

There are some antigens normally found only in some peripheral tissues. Negative selection of thymocytes for these self antigens occurs in (X) via (Y) cells, under direction of (Z).

A 
X = thymus
Y = epithelial cells
Z = (transcription factor) AIRE
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6
Q

Peripheral tolerance develops in (central/peripheral) lymph organs. Potential outcomes of recognizing (X) are:

A

Peripheral;
X = self-antigens

  1. Apoptosis
  2. Anergy
  3. Suppression by Tregs
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7
Q

In self-reactive T cell, activation “signal 1”, aka (X), is received. Which mechanisms in place to allow anergy of this cell?

A

X = peptide:MHC and TCR interaction

  1. No signal 2 via sufficient CD28 engagement (low B7 on APC, since no PAMP/DAMP)
  2. T-cell inhibitory receptors engage B7 on APCs
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8
Q

Autoreactive T cell can become anergic thanks to (X) inhibitory (receptors/ligands) that bind (Y).

A

X = CTLA-4 and/or PD-1
Receptors
Y = B7 molecule on APC

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9
Q

Anergy of autoreactive T cell: (X) molecule on APC has higher affinity for (stim/inhib) receptors, (Y) on T cell.

A

X = B7
Inhibitory
Y = CTLA-4 and PD-1

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10
Q

Tregs can suppress autoreactive T cells in (central/peripheral) lymph organs. They do this by:

A

Peripheral;

Secreting cytokines (IL-10 and TGF-beta)

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11
Q

Apoptosis of T cells occur through which pathways?

A
  1. Mitochondrial (intrinsic)

2. Death receptor (extrinsic)

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12
Q

Extrinsic, (X), pathway of apoptosis involves (Y) being upregulated by (Z).

A 
X = death receptor
Y = Fas (receptor) and FasL (ligand)
Z = T cell
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13
Q

Receptor-editing of (X) cells in (central/peripheral) lymph organs is done by rearranging (Y).

A

X = self-reactive B
Central;
Y = IgL locus

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14
Q

After receptor-editing of B cell, if the second (X) is still autoreactive and (Y), it dies via apoptosis.

A 
X = BCR
Y = directed against cell-bound antigen
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15
Q

After receptor-editing of B cell, if the second (X) is still autoreactive and (Y), it becomes anergic.

A 
X = BCR
Y = directed against soluble antigen
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16
Q

Autoreactive B cells in peripheral lymph organs are dealth with in which way(s)?

A
  1. Anergy
  2. Treg or inhibitory receptor suppression
  3. Apoptosis (extrinsic pathway)
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17
Q

Define autoimmunity.

A

Reaction to self-antigens

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18
Q

In general, development of autoimmunity requires presence of which factors?

A
  1. Genetic susceptibility

2. Environmental trigger

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19
Q

T/F: Some MHC genes, if defective, can by themselves cause autoimmune disease.

A

False

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20
Q

T/F: There are some genes that, if defective, can by themselves cause autoimmune disease.

A

True

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21
Q

(MHC/non-MHC) genes represent largest genetic association with autoimmunity.

A

MHC

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22
Q

Defective MHC alleles in autoimmune diseases likely cause MHC proteins to perform (X) function improperly.

A

X = presentation of self-peptide to T cells

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23
Q

Defective non-MHC alleles in autoimmune diseases likely “release the brakes” on immune system. This allows:

A

Development/propagation of self-reactive T and B cells

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24
Q

Ankylosing spondylitis is disease associated with (X) gene and relative risk value of (Y).

A 
X = MHC;
Y = 90
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25
Q

Rheumatoid arthritis is disease associated with (X) gene and relative risk value of (Y).

A 
X = MHC or PTPN22
Y = 4-12 (for MHC allele)
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26
Q

What does it mean if your relative risk for disease is 90 when you have certain allele?

A

You’re 90x more likely to develop disease (if you have that allele)

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27
Q

Type I diabetes is disease associated with (X) gene and relative risk value of (Y).

A 
X = MHC (and some non-MHC) 
Y = 35 (for MHC allele)
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28
Q

Pemphigus vulgaris is disease associated with (X) gene and relative risk value of (Y).

A 
X = MHC
Y = 14
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29
Q

Tissue injury can trigger autoimmunity by inducing (X) cells to provide (Y) signal to (Z) cells.

A 
X = APCs
Y = co-stimulatory (signal 2)
Z = autoreactive T cells
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30
Q

Define immunization.

A

The process of inducing OR providing immunity by artificial means

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31
Q

Vaccination is (active/passive) immunization.

A

Active

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32
Q

Active immunization involves administration of (X).

A

X = non-pathogenic microbes/microbial products

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33
Q

Passive immunization involves administration of (X).

A

X = antibodies

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34
Q

Pros of active immunization.

A

Long-lasting and immunologic memory formed

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35
Q

Cons of active immunization.

A

Takes time to develop

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36
Q

Pros of passive immunization.

A

Immediate protection provided

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37
Q

Cons of passive immunization.

A

Temporary (till Ab are catabolized)

38
Q

Which vaccine type mimics a natural infection? What are the pros of this vaccine type?

A

Live attenuated (weakened) vaccine;

Pros: long-lasting; and low dose needed

39
Q

Cons of live attenuated vaccine.

A

Possibility of reversion to pathogenic form

40
Q

Pros of dead/inactivated vaccine type.

A

More stable and safe (than live vaccines)

41
Q

Cons of dead/inactivated vaccine type.

A

Need higher dose and (since short-lived immunity) need more booster immunizations

42
Q

T/F: Live vaccines can be replicated in host cells.

A

True

43
Q

Live attenuated vaccines should NOT be given to patients with:

A

T-cell immunodeficiency

44
Q

List some examples of live attenuated vaccines.

A
  1. Measles/mumps/rubella
  2. Chickenpox
  3. Rotavirus
45
Q

Toxoids are examples of (X), which is a subcategory of (live/dead) (Y).

A

X = subunit vaccines
Dead;
Y = vaccines

46
Q

Toxoids are used in cases where (X) causes the disease. Toxoids are made/prepared by treatment of (Y) with mild (Z).

A 
X = Y = toxin
Z = formaldehyde
47
Q

Toxoids: the idea is to alter (X) enough to destroy toxicity, but to leave (Y).

A 
X = toxin
Y = structure (so Ab can react with it)
48
Q

Conjugate vaccines key function is to alter (X) by:

A

X = T-independent antigens

Adding protein component (making them T-dependent)

49
Q

Conjugate vaccines allow presentation of microbe by (X) cell on (Y) to (Z) cell.

A 
X = B
Y = MHC class II
Z = CD4 T
50
Q

T/F: Conjugate vaccines allow generation of memory B and memory CD4 T cells.

A

True

51
Q

Adjuvants are substances that (enhance/prevent) (X) by:

A

Enhance
X = immunogenicity
Making vaccine insoluble

52
Q

Give example of an adjuvant.

A

Aluminum hydroxide

53
Q

Vaccination of majority provides immunity to the unprotected/unvaccinated individuals. This phenomenon is called:

A

Herd immunity

54
Q

List the general types of immunotherapeutics.

A
  1. Ab
  2. Recombinant cytokines
  3. Recombinant cytokine inhibitors
55
Q

(Polyclonal/monoclonal) Ab reflect body’s normal Ab response. It’s a (homo/hetero)-geneous mixture that’s (manufactured/derived) from (X). This makes the supply (limited/unlimited).

A 
Polyclonal;
Heterogeneous;
Derived
X = plasma or serum
Limited
56
Q

(Polyclonal/monoclonal) Ab contains identical Ab molecules. It’s a (homo/hetero)-geneous mixture that’s (manufactured/derived) from (X). This makes the supply (limited/unlimited).

A 
Monoclonal
Homogeneous 
Manufactured
X = B cell fusion with cancer cell (hybridoma)
Unlimited
57
Q

T/F: Monoclonal Ab suspension has only one targeted epitope.

A

True

58
Q

Immunotherapeutics: list the types of diseases/conditions that Ab are used to treat.

A
  1. Infections
  2. Cancer
  3. B cell immunodeficiencies and autoimmune diseases
59
Q

How might (poly/mono)-clonal Ab be used in cancer therapy?

A

Monoclonal Ab targeted at specific cancer cell antigen/marker

60
Q

Adalimumab is a(n) (X), targeted against (Y).

A 
X = anti-TNF (monoclonal) Ab
Y = TNF (cytokine)
61
Q

Immunotherapeutics: In general, recombinant cytokines can be given to patients who…

A

Are deficient or need extra

62
Q

Which immune therapy is used to treat IL-12 receptor deficiency? Explain the logic.

A

Recombinant cytokine (IFN-gamma) because deficiency in IL-12 receptor leads to lack of Th1 cell development (thus deficiency in IFN-gamma)

63
Q

IL-1 receptor antagonist is an example of (X) type of immunotherapeutic. What’s its role in treating some (Y) diseases?

A 
X = recombinant cytokine inhibitor
Y = autoimmune

Blocks IL-1 receptor (anti-inflammatory)

64
Q

Etanercept is really just a(n) (X). What’s its role in treating some (Y) diseases?

A 
X = soluble TNF receptor
Y = autoimmune

Binds TNF, preventing its binding to normal TNF receptors (anti-inflammatory)

65
Q

Immunotherapeutics: making soluble receptors is done by fusing (X) with (Y). Which key benefit does this have?

A 
X = extracellular part of receptor
Y = Fc region of IgG

Long blood half-life

66
Q

What’s the main point of the (X) number of stages in clinical trials?

A

X = 3

Determine safety and efficacy of drug (vaccine/immunotherapeutic)

67
Q

Clinical trials Phase I has (few/many) subjects and key point is to assess:

A

Few;

Safety and potential efficacy

68
Q

Which clinical trial phase(s) assess efficacy against disease?

A

Phases II and III

69
Q

Which clinical trial phase(s) involves many subjects, divided into groups?

A

Phase III

70
Q

Patient with B cell deficiency should be treated with which specific type of immunotherapy?

A

Intravenous immune globulin (IVIG)

71
Q

Which immunotherapy is used for post-exposure treatment (such as rabies)?

A

Specific immune globulin (against a particular microbe)

72
Q

The key interaction that immunodiagnostics is based on is:

A

Ab-antigen

73
Q

List the two categories of “immunodiagnostics”

A
  1. Hemagglutination

2. Immunoassays (ft. lables)

74
Q

What’s an analyte?

A

The substance (either Ab or antigen) that you want to analyze/detect

75
Q

Hemagglutination is simply the (X) of (Y) by (Z).

A 
X = cross-linking
Y = RBCs
Z = Ab
76
Q

List some labels used in immunoassays to tag (Ab/antigen).

A

Either Ab or antigen;

  1. Chemiluminescent compounds
  2. Enzymes
  3. Fluorochrome
77
Q

In immunoassays, the antigen-Ab reaction is labeled (directly/indirectly).

A

Can be direct or indirect

78
Q

Anti-human Ig Ab are used to detect (X) (directly/indirectly).

A

X = Ab-antigen reaction

Indirectly

79
Q

The idea behind anti-human Ig Ab is that (X) from one species can be (Y) in another species.

A 
X = Ab
Y = antigens
80
Q

In indirect labeling of immunoassays, the (X) is the primary Ab and the (Y) is the secondary Ab. Star the one that’s labeled.

A 
X = patient's Ab
Y = anti-Ig Ab*
81
Q

In ELISA to detect patient’s specific IgG, the wells are coated with (X).

A

X = antigen (to specific IgG)

82
Q

In ELISA to detect patient’s specific IgG, the wells are first coated/washed, and then (X) is added.

A

X = patient serum (IgG Ab)

83
Q

In ELISA to detect patient’s specific IgG, what’s added after the patient’s (X)?

A

X = serum (IgG Ab)

The enzyme-conjugated anti IgG (secondary Ab)

84
Q

In ELISA to detect patient’s specific IgG, what’s the final addition step, allowing signal detection?

A

Add substrate to the enzyme (enzyme will convert colorless substrate into colored product)

85
Q

List the basic 4 steps of immunoassay. Star any optional steps.

A
  1. Antigen on solid support
  2. Primary Ab
  3. Secondary Ab*
  4. Detect
86
Q

Define “titer”.

A

Highest serum dilution that yields signal above negative (control)

87
Q

Western blot provides information about (X), unlike other immunoassays.

A

X = MW

88
Q

Immunofluorescence/immunohistochemistry provides information about (X), unlike other immunoassays.

A

X = morphology

89
Q

Which immunoassay analyzes single cells in suspension?

A

Flow cytometer

90
Q

T/F: Flow cytometry provides quantitative information.

A

True

91
Q 
Western blotting is a technique 
that uses (X) to highlight the (Y) of (Z) in cell extracts.
A 
X = Ab
Y = size and amount
Z = protein

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