MI 05a: Tolerance and Autoimmunity Flashcards by Nuna H

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

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

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

Central;
X = self-antigen

Apoptosis
Treg development
B cell receptor editing

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

X = CD4 T cells

CD25 (alpha chain of IL-2)
FoxP3 (transcription factor)

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

Outside;
Suppress

X = lymphocytes and APCs

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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).

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

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

Peripheral;
X = self-antigens

Apoptosis
Anergy
Suppression by Tregs

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

X = peptide:MHC and TCR interaction

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

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

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

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

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

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

Peripheral;

Secreting cytokines (IL-10 and TGF-beta)

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Apoptosis of T cells occur through which pathways?

Mitochondrial (intrinsic)

2. Death receptor (extrinsic)

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

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

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

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

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

X = BCR
Y = directed against cell-bound antigen

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

X = BCR
Y = directed against soluble antigen

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

Anergy
Treg or inhibitory receptor suppression
Apoptosis (extrinsic pathway)

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Define autoimmunity.

Reaction to self-antigens

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

Genetic susceptibility

2. Environmental trigger

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

False

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

True

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

MHC

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

X = presentation of self-peptide to T cells

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

Development/propagation of self-reactive T and B cells

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

X = MHC;
Y = 90

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

``` X = MHC or PTPN22 Y = 4-12 (for MHC allele) ```

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

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

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

``` X = MHC (and some non-MHC) Y = 35 (for MHC allele) ```

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

``` X = MHC Y = 14 ```

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

``` X = APCs Y = co-stimulatory (signal 2) Z = autoreactive T cells ```

Define immunization.

The process of inducing OR providing immunity by artificial means

Vaccination is (active/passive) immunization.

Active

Active immunization involves administration of (X).

X = non-pathogenic microbes/microbial products

Passive immunization involves administration of (X).

X = antibodies

Pros of active immunization.

Long-lasting and immunologic memory formed

Cons of active immunization.

Takes time to develop

Pros of passive immunization.

Immediate protection provided

Cons of passive immunization.

Temporary (till Ab are catabolized)

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

Live attenuated (weakened) vaccine; Pros: long-lasting; and low dose needed

Cons of live attenuated vaccine.

Possibility of reversion to pathogenic form

Pros of dead/inactivated vaccine type.

More stable and safe (than live vaccines)

Cons of dead/inactivated vaccine type.

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

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

True

Live attenuated vaccines should NOT be given to patients with:

T-cell immunodeficiency

List some examples of live attenuated vaccines.

1. Measles/mumps/rubella 2. Chickenpox 3. Rotavirus

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

X = subunit vaccines Dead; Y = vaccines

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

``` X = Y = toxin Z = formaldehyde ```

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

``` X = toxin Y = structure (so Ab can react with it) ```

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

X = T-independent antigens Adding protein component (making them T-dependent)

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

``` X = B Y = MHC class II Z = CD4 T ```

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

True

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

Enhance X = immunogenicity Making vaccine insoluble

Give example of an adjuvant.

Aluminum hydroxide

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

Herd immunity

List the general types of immunotherapeutics.

1. Ab 2. Recombinant cytokines 3. Recombinant cytokine inhibitors

(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).

``` Polyclonal; Heterogeneous; Derived X = plasma or serum Limited ```

(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).

``` Monoclonal Homogeneous Manufactured X = B cell fusion with cancer cell (hybridoma) Unlimited ```

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

True

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

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

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

Monoclonal Ab targeted at specific cancer cell antigen/marker

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

``` X = anti-TNF (monoclonal) Ab Y = TNF (cytokine) ```

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

Are deficient or need extra

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

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

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

``` X = recombinant cytokine inhibitor Y = autoimmune ``` Blocks IL-1 receptor (anti-inflammatory)

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

``` X = soluble TNF receptor Y = autoimmune ``` Binds TNF, preventing its binding to normal TNF receptors (anti-inflammatory)

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

``` X = extracellular part of receptor Y = Fc region of IgG ``` Long blood half-life

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

X = 3 Determine safety and efficacy of drug (vaccine/immunotherapeutic)

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

Few; | Safety and potential efficacy

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

Phases II and III

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

Phase III

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

Intravenous immune globulin (IVIG)

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

Specific immune globulin (against a particular microbe)

The key interaction that immunodiagnostics is based on is:

Ab-antigen

List the two categories of "immunodiagnostics"

1. Hemagglutination | 2. Immunoassays (ft. lables)

What's an analyte?

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

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

``` X = cross-linking Y = RBCs Z = Ab ```

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

Either Ab or antigen; 1. Chemiluminescent compounds 2. Enzymes 3. Fluorochrome

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

Can be direct or indirect

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

X = Ab-antigen reaction | Indirectly

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

``` X = Ab Y = antigens ```

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

``` X = patient's Ab Y = anti-Ig Ab* ```

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

X = antigen (to specific IgG)

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

X = patient serum (IgG Ab)

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

X = serum (IgG Ab) The enzyme-conjugated anti IgG (secondary Ab)

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

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

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

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

Define "titer".

Highest serum dilution that yields signal above negative (control)

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

X = MW

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

X = morphology

Which immunoassay analyzes single cells in suspension?

Flow cytometer

T/F: Flow cytometry provides quantitative information.

True

``` Western blotting is a technique that uses (X) to highlight the (Y) of (Z) in cell extracts. ```

``` X = Ab Y = size and amount Z = protein ```

MI 05a: Tolerance and Autoimmunity Flashcards

(91 cards)