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ACAAI Review for the Allergy/Immunology Boards > Chapter 1, Section 1. Basic Science > Flashcards

Chapter 1, Section 1. Basic Science Flashcards

1
Q

What genes are associated with MHC-II

A

HLA-DP, HLA-DQ, HLA-DR

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2
Q

How many isotypes of human IgG are there

A

4 - IgG1, IgG2, IgG3, IgG4

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3
Q

Where does Omalizumab bind

A
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4
Q

What kind of bond is there between Ig heavy-heavy and heavy-light chains

A

disulfide bonds

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5
Q

What is Ig affinity

What is Ig avidity

A

strength of binding between the antibody and the epitope. It is indicated by the Ksubd. A numerically lower Ksubd indicates higher affinity

Avidity is the net effect of affinity and valence. It is an estimate of the overall strength of the binding between Ig and antigen. A low-affinity IgM can produce a high-avidity interaction by simultaneous binding to multiple antigen epitopes through 10 contact sites on each IgM molecule

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6
Q

Titermax adjuvant - what copolymers are in it

A

Copolymers polyoxypropylene (POP) and polyoxyethylene (POE)

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7
Q

What are the nucleotides (4)

Which are purines? Which are pyrimidines?

A

adenine (A), guanine (G), thymine (T), cytosine (C)

A,G are purines

T,C are pyrimidines

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8
Q

How does lack of costimulation function in tolerance

A

lack of costimulation, or lack of an innate immune system response to the antigen, blunts the required upregulation to produce costimulation (a second signal). T lymphocytes will recognize the antigen but receive no support to activate. If this happens repeatedly where the cell is recognized but no costimulation is forthcoming the lymphocyte becomes unresponsive to that antigen (anergic)

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9
Q

Once the TCR-antigen HLA complex is formed, how does activation occur:

A

activation requires a second signal or costimulation

the most important cytokine is IL-2 and its receptor CD25

proliferation is clonal; it is stimulated by IL-2, clonal expansion preserves the specificity of the T lymphocyte for its particular antigen

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10
Q

What cytokines (2) do Tregs need to survive

A

IL-2 and TGFbeta

tolerance is maintained in general by IL-10 (turns off innate cells) and TGFbeta (turns off innate and lymphoid cells)

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11
Q

How many constant regions are there in IgG, IgA, and IgD

How many constant regions are there is IgM and IgE

A

3

4

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12
Q

What is the TCR complex made up of

A

TCR, CD3, two zeta chains

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13
Q

how are somatic mutations passed down

A

these occur with cells outside of the reproductive system, so do not get passed to subsequent generations. However, a mutation early enough in the process can affect a lot of the cells and this can cause disease - mosaicism

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14
Q

What type of molecule transports amino acids to ribosome

A

tRNA

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15
Q

Lck

A

an SRC family kinase, noncovalently associated with CD4 and CD8

basically turns on (phosphorylates) the zeta and CD3 proteins by way of their ITAMs

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16
Q

Review the MHC class II antigen-processing pathway

A
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17
Q

What cytokines are associated with MHC class I cells

A

interferon alpha, interferon beta, and interferon gamma

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18
Q

What part of the TCR imparts the most significant sequence variability

A

the alpha-beta CDR3 (just like in antibodies)

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19
Q

what type of molecule is copied from DNA and travels to ribosome

A

mRNA

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20
Q

What genes are associated with MHC-1

A

HLA-A, HLA-B, HLA-C

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21
Q

IP3

A

1,4,5 triphosphate

more importantly, the generation of IP3 stimulates an increase in cytosolic calcium from the ER.

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22
Q

For the ADAM33 gene, name the associated protein, the protein function, and relevance in atopy

A

type 1 transmembrane protein, cell-to-cell interactions, increased risk of asthma and bronchial hyperresponsiveness

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23
Q

What do effector CD4 cells do (3)

A

induce differentiation of T lymphocyte response to either Th1, Th2, Th17

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24
Q

What is the most variable part of the Ig molecule

A

CDR3.

VsubL and VsubH form the antigen-binding sites that consist of complementarity-determining regions which account for antibody diversity. There are 3 CDRs in each V region

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25
Q

Where does peripheral tolerance occur

A

this occurs in the peripheral tissues when a mature lymphocyte encounters a self-antigen

same as before, if the T cell reacts to self it can either 1) undergo apoptosis 2) become anergic or 3) become Treg cells

if a B cell reacts to self in the periphery, it will either become anergic or be deleted through apoptosis

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26
Q

What is the toxin associated with Strep Pyogenes superantigen disease

A

SPE-C - strep toxic shock syndrome

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27
Q

What state of being is a T cell in when it recognizes an antigen but does not receive costimulatory signals

A

this is anergy

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28
Q

T/F T cells only recognize antigens that are presented as part of the MHC complex (MHC restriction). This restricts them to ________

A

T, peptide

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29
Q

Mutations in SAP (what is it?) cause what disease

A

SAP = SLAM-associated protein

brings SLAM and Fyn together. downstream Fyn binds to CD3

mutations lead to X-linked lymphoproliferative syndrome (XLPS)

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30
Q

Review T-Cell Differentiation

A
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31
Q

What happens to cells repeatedly presenting self-antigen without innate response

what overall protein system does this involve

A

They have Fas which interacts with FasL on the T cell and this can delete the self-reactive T cell or cause the death of the activating cell

This involves the caspase system

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32
Q

Review Summary of T and B Cell Tolerance

A
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33
Q

T/F Alternative splicing changes Ig from transmembrane to secretory form

A

True

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34
Q

NFkappaB

A

transcription factor essential for cytokine synthesis and plays an important role in lymphocyte development, neoplasms, and formation of secondary lymphoid organs

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35
Q

What causes ALPS (autoimmune lymphoproliferative syndrome)

A

mutations in Fas and caspase system in general. The cells accumulate and don’t know when to die.

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36
Q

Key Fact

Mutations in what gene leads to APS (autoimmune polyglandular syndrome)

A

AIRE gene

lymphocytes fail to have tolerance, they are not deleted or tolerated to endocrine-related self antigens. The endocrine organs are attacked by autoreactive T lymphocytes and autoantibodies

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37
Q

Review “Costimulator Expression and Function”

A
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38
Q

Define “Immunogen”

A

molecule that induces an immune response (used interchangeably with “antigen”)

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39
Q

For the 5q22-32 gene, name the associated protein, the protein function, and relevance in atopy

A

CD14, LPS receptor, both increased/decreased risk of asthma/atopy

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40
Q

Rac-GTP

A

another molecule activated by another GDP/GTP exchange that activates JNK to phosphorylate Jun, which also turns on AP-1

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41
Q

What is a superantigen

A

antigens that activate a large number of polyclonal T lymphocytes by binding outside the MHC antigen cleft and cause massive cytokine release

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42
Q

Nucleic Acid Antigens

What immune cells are involved (3)

What surface molecules are involved? (3)

Prototypical vaccines (1)

A

Immune cells = B cells, CTLs, DC

Surface molecules = MHC Class I, MHC Class II, TLR

Vaccines = DNA vaccines in clinical trials

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43
Q

ZAP-70

deficiency in this leads to what clinical syndrome

A

Syk family kinase

deficiency leads to a SCID with NO CD8 cells or T-lymphocyte function, but normal B lymphocytes and NK cells.

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44
Q

How does T-lymphocyte central tolerance work

A

A T-lymphocyte precursor is exposed to a self-antigen in the thymus. First, the T cell has to bind well enough to MHC (positive selection). Secondly it has to not react to self-antigens (negative selection)

If it does react to self, it either undergoes apoptosis or develops into a Treg cell

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45
Q

How does B cell tolerance work

A

precursor B cells are exposed to self-antigen in the bone marrow during development. If B cells are exposed to self one of three things can happen: 1) apoptosis (negative selection) 2) receptor editing 3) anergy

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46
Q

What is the inheritance pattern of MHC molecules

A

MHC molecules are co-dominant, which means that a given individual expresses one haplotype from each parent. This means that MHC from both parents is expressed on cell surfaces

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47
Q

What are the two general forms of Ig

A

membrane bound

secreted

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48
Q

For the 3p21-22 gene, name the associated protein, the protein function, and relevance in atopy

A

CCR5, chemokine receptor, protection against nonallergic asthma

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49
Q

What do activated T cells become when they grow up

A

They become effector or memory T cells

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50
Q

What cellular markers do T cells in the thymus carry

A

double negative (CD4- and CD8-)

CD3+

after proceeding through education in the thymus, the cells become single positive

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51
Q

What is the structure of the Ig molecule

A

Ig molecule is a polypeptide heterodimer composed of two identical light chains and two identical heavy chains connected by disulfide bonds

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52
Q

NFAT

A

nuclear factor of activated T lymphocytes (NFAT), antigen-activated transcription factor for expressing genes encoding for cytokines (including IL-2, IL-4, TNF) usually in association with AP-1 (transcription factor)

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53
Q

Review this table on leukocyte Fc receptors

A
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54
Q

Freund’s adjuvant - what is it

A

emulsified in bacterial products (BCGs)

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55
Q

What is the CD deficiency that leads to SCID (key fact)

A

CD3 deficiency

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56
Q

What is the general structure of the alpha-beta TCR

A

heterodimer of alpha and beta chain, each with two Ig-like domains. Each alpha and beta chain consist of a variable (V) and constant (C) domain, a transmembrane hydrophobic region, and a short cytoplasmic tail with NO SIGNALING ability (requires accessory molecules for signal transduction)

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57
Q

Heavy chains are designated by what letters of the Greek alphabet

A

gamma (G), alpha (A), mu (M), epsilon (E), delta (D)

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58
Q

Key Fact

In B cell central tolerance, what light chain subunit comes first

A

the kappa light chains are rearranged first in central b lymphocyte tolerance. If the receptor reacts too much to self then then the process of receptor editing is started with lambda chains

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59
Q

Key fact - what MHC receptor do CD8 cells go for? How about CD4 cells

A

CD8 - MHC I

CD4 - MHC II

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60
Q

What happens with too-little Ig glycosylation

What happens with too-little Ig galactosylation

What happens with sialic acid enrichment in IVIG

A

poor function, can’t bind to Fc receptors, can’t activate complement

associated with hyper-inflammatory states

this significantly increases IVIG anti-inflammatory activity

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61
Q

Protein Antigens

What immune cells are involved (3)

What surface molecules are involved? (2)

What is the B-cell response? (3)

Prototypical vaccines (2)

A

Immune cells = B-2 cells, T cells, “T-cell-dependent”

Surface molecules = MHC Class I, MHC Class II

B-cell response = isotype switch, affinity maturation, induced memory response

Vaccines = Diphtheria, Tetanus

62
Q

T/F Somatic hypermutation leads to changes in the V but not the C regions

A

True

63
Q

What are virus strategies to evade MHC class I presentation?

Give examples . . .

A

HSV can block TAP transportation

CMV can remove MHC class I from the ER

64
Q

What cytokines are associated with MHC II

A

interferon gamma only

65
Q

How are light chains (on Ig) identified

A

they are identified by their C regions: kappa is coded on chromosome 2 and lambda is coded on chromosome 22

an Ig molecule has either KK or LL but never 1 of each. Similarly, a B lymphocyte will produce only K chains or L chains, never both

66
Q

For the 5q31 gene, name the associated protein, the protein function, and relevance in atopy

A

IL-13, cytokine that induces IgE secretion, mucous production, and collagen synthesis. Increased risk of asthma, bronchial hyperresponsiveness, SPT responsiveness. Linked to response to Singulair

67
Q

What is “epigenetics”

A

changes in gene function that occur without a change in the sequence of DNA

often occur due to environmental interactions that cause methylation and histone modification

68
Q

Lipid Antigens

What immune cells are involved (2)

What surface molecules are involved? (2)

A

Immune cells = NK cells, gamma delta cells

Surface molecules = MHC-like, CD1(NKT)

69
Q

For the ADRB2 gene, name the associated protein, the protein function, and relevance in atopy

A

B2 adrenergic receptor, adrenaline/noradrenaline receptor. Relevance is Arg/Arg phenotype with decreased albuterol response compared with Gly/Gly phenotype at residue 16

70
Q

What cells have MHC class I

A

almost all nucleated cells

71
Q

How can the ratio of K to L bearing lymphocytes help oncologists

A

the ratio of K-bearing lymphocytes (remember, the kappa chain is rearranged first, the lambda only if receptor editing is needed) to lambda bearing lymphocytes is an indication of clonality

therefore, it is useful to diagnosing and typing B-lymphocyte lymphomas

72
Q

What is a tolerogen

A

A tolerogen is an antigen that induces tolerance

A foreign antigen that becomes a tolerogen does so conditionally (only does so at a certain amount of antigen concentration, for example)

73
Q

What are antibody constant regions

A

These are CsubH and CsubL. Only CsubH does any effector functions (binding to Fc receptors, binding complement)

74
Q

How do B cells get activated (in general)

A

They need T cell help, because antigens cannot cross-link the BCR on their own

without the T cell, they will become anergic or induced to apoptosis

75
Q

What do Treg cells express (3)

A

CD4, CD25, FoxP3

76
Q

What are “Bare Lymphocyte Syndromes”

A

“Bare Lymphocytes” are lymphocytes without class I or class II MHC. So, “Bare Lymphocyte Syndromes” refer to a MHC class I or MHC class II deficiency

77
Q

What is immunogenic tolerance

A

Immunogenic tolerance is unresponsiveness to an antigen

this can be to self-antigens (self-tolerance) or foreign antigens

self-tolerance is part of the normal immune system education

78
Q

What kind of epitopes are recognized by T cells

A

linear determinents of amino acids only

length limited by MHC binding (MHC I = 8-11, MHC II 10-30)

79
Q

Why do SNPs matter to allergists

A

several predispose to higher risk of atopy and differing response of medications for allergic processes

80
Q

Hapten

A

small-molecule antigen that, when bound to a larger carrier such as a protein, is capable of eliciting the production of antibodies; hapten-specific B cells interact with carrier-specific T cells to generate these antibodies; once an antibody to a hapten is generated, the carrier is no longer needed to simulate an immune response

81
Q

What mutation occurs in IPEX

A

FoxP3 mutation, as in IPEX, causes immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome

fatal autoimmune disorder characterized by triad of watery diarrhea, eczema, and endocrinopathy

82
Q

Sos

A

a GDP/GTP exchanger

in the attached picture, the SOS is simply termed the “GDP/GTP exchange factor”, but is in fact the same thing

83
Q

What signaling molecule is required for T-lymphocyte activation and maturation (both CD4 and CD8)

A

Lck

(part of a Src family tyrosine kinase)

phosphorylates the ITAMs in CD3 and zeta proteins so that ZAP protein is recruited

84
Q

What is the definition of “antigen”

A

any substance that gives rise to a specific immune response or is recognized by lymphocytes or antibodies

85
Q

T/F T cells recognize lipids, nucleic acids, polysaccharides that are presented by MHC molecules

A

F, these entities are not presented by T cells and are thus not recognized by T cells

86
Q

How does receptor editing work

A

This involves reactivation of RAG1 and RAG2 when a high-affinity self-antigen is recognized by the BCR

The RAG enzymes will delete the previously rearranged VJ exon and give the BCR a new light chain. As a result, this self-reactive B cell will have a new specificity.

If this next recombination recognizes self too - the B cell will be deleted by apoptosis, or possibly just become anergic if the self-antigen is of low concentration

87
Q

CRAC

A

calcium release activated calcium channel, on the cell membrane

it’s necessary for more calcium to come in the cell for various PKC transcription factors to come into being (notably NFAT)

88
Q

Review the Functional Features of IgG

A
89
Q

For the Filaggrin gene, name the associated protein, the protein function, and relevance in atopy

A

Filaggrin, essential for epidermal barrier, increased risk of eczema/asthma

90
Q

What are some differences between alpha beta and gamma delta T lymphocytes

A

gamma delta cells do not have CD4 or CD8

they are NOT HLA RESTRICTED

they are a bridge between innate and acquired immunity

91
Q

What are adjuvants

A

molecules given in vaccines to enhance the body’s immune response to an antigen; typically this involves activating the innate immune system leading to costimulatory expression/cytokine production leading to an adaptive response

92
Q

For the 17q12-21 gene, name the associated protein, the protein function, and relevance in atopy

A

ORMDL3, unknown function, increased risk of asthma

93
Q

calcineurin

A

activator of nuclear factor of activated T lymphocytes (NFAT) by dephosphorylation, allowing it to travel to the nucleus

94
Q

Antigen is a contraction of what two words?

A

Antibody Generator

95
Q

review “types of mutations”

A
96
Q

Key Facts

What is the only Ig to cross the placenta

What is the Ig with highest plasma concentration

What is the Ig with the highest whole body concentration and daily production

What secretes the poly-Ig receptor

A

IgG (binds to neonatal FcRn)

IgG

IgA

synthesized by the mucosal epithelial cells and helps transport IgA via vesicles to the luminal surface

97
Q

Which nucleotides are in RNA

A

The same as DNA, but there is uracil (U) instead of T

A, G, U, C

98
Q

Where in the body does central tolerance occur

A

Central tolerance occurs in the lymph organs (thymus for t cells, bone marrow for b cells)

99
Q

Key Fact - What IgG subclass has the shortest half-life

A

IgG3

100
Q

How do nucleotides fit together as far as base pairing

A

A clicks with T

G clicks with C

101
Q

Review the structure of class I and class II molecules

A
102
Q

LAT

A

phosphorylation of LAT recruits adapter proteins that mediate different signaling pathways

103
Q

What enzyme is stimulated with CD40L-CD40 interactions

A

stimulates activation-induced cytosine deaminase (AID), crucial for somatic mutation and isotype switching

104
Q

What is a mutation

A

a change in the nucleotide sequence of genes

105
Q

What cells have MHC class II

A

APCs - dendritic cells, macrophages, B cells

106
Q

What are the three toxins associated with Staph Aureus superantigen disease

A

SEB - food poisoning SEC2 - food poisoning TSST - toxic shock syndrome

107
Q

What are SNPs

A

single nucleotide polymorphism, widely used in GWAs (genome-wide association studies)

this is a variation in DNA sequence that occurs when a single nucleotide differs from the normal

108
Q

What kinds of epitopes are recognized by B cells

A

linear determinants or tertiary structure in native conformation

carbohydrates, amino acids, nucleic acids, phospholipids

109
Q

Calmodulin

A

ubiquitous, calcium-dependent regulatory protein that binds calcium and interacts with calcineurin

110
Q

what is Rheumatoid factor

A

antibody against the Fc portion of IgG. It is most commonly IgM but it can be any other isotype

111
Q

What does HLA-DM have to do with MHC class II

A

HLA-DM is an intracellular protein involved in class II antigen processing. It removes CLIP and thus allows antigenic peptides to be loaded in the MHC binding cleft.

It is not a component of MHC class II

112
Q

Fyn

A

Src family kinase, noncovalently associated with CD3

fyn is attached physically to the CD3 proteins in T cells

113
Q

What do activated CD8 cells do

A

they become cytolytic

114
Q

T/F Class switch recombination changes the V but not the C regions

A

False

115
Q

Where in the cell is DNA stored (easy question)

A

nucleus

116
Q

What is the key component of humoral immunity and what produces it

A

Igs - produced by B lymphocytes and plasma cells

117
Q

Are SNPs mutations

A

these are not considered mutations, as they occur more frequently in noncoding DNA sequences and also occur more often than mutations

118
Q

What is anergy

A

Anergy is a state of unresponsiveness to antigenic stimulation; the antigen is recognized by the immune cell but weak signaling (owing to a lack of costimulation) leads to anergy

119
Q

What is SLAM and why is it important

A

SLAM (signaling lymphocytic activation molecule) binds to SLAM-associated protein (SAP) which links it to Fyn.

Fyn is linked to CD3 proteins in T cells

so, basically, SLAM is necessary for T-cell signaling

120
Q

how are germ-line mutations passed down

A

via reproductive cells

121
Q

What kind of chemical binding is used in antigen recognition by Ig

A

reversible, noncovalent binding through the Ig V regions

antibody binds to effector cells through the Fc region

122
Q

what molecule, downregulated with chronic antigen recognition, leads B-lymphocytes home to lymph nodes to interact with T cells

A

CXCR5

123
Q

Polysaccharide Antigens

What immune cells are involved (4)

What is the B-cell response? (4)

Prototypical vaccines (2)

A

Immune cells = Marginal zone B cells, B-1 cells, Macrophages, “T-cell-independent”

B-cell response = no isotype switch, no affinity maturation, limited memory response, predominantly IgM

Vaccines = MSPV4 (Menomune), PPSV23

124
Q

What are SNPs useful for

A

these tend to differ between different geographic and ethnic groups, so they are useful as markers for human genetic variations between groups and their differing susceptibility to various diseases

125
Q

What protein is key in T cell apoptosis

A

BIM - proapoptotic member of the Bcl-2 family. Leads to apoptosis via mitochondrial pathway

126
Q

Ribi adjuvant system

A

Squalene-Tween80-water and oil emulsification

127
Q

What type of molecule combines with protein to make ribosomes

A

rRNA

128
Q

What processes maintain peripheral T-cell anergy at the cellular level

A

blockade of TCR signalling, ubiquitin ligases (which target proteins for degradation), and inhibitor costimulatory molecules (CTLA4, PD-1)

129
Q

Key Fact - On what chromosome are MHC molecules coded

What are the three regions that on this chromosome that encode the MHC

A

Chromosome 6

Class II, Class III, Class I

130
Q

What is an epitope

A

Antigenic determinant. It is the antigenic component identified by a unique antibody. A single antigen may have many different epitopes.

131
Q

What receptor enables NK-T cells to recognize lipids

A

CD1

132
Q

What do accessory molecules for the TCR contain

A

immunoreceptor tyrosine-based activation motifs (ITAMs)

133
Q

Incomplete Freund’s adjuvant - what is it

A

water in oil emulsificaton

134
Q

what is transcription? What is translation?

A

transcription is synthesis of mRNA from DNA

translation is the synthesis of proteins from mRNA

135
Q

Aluminum adjuvant - where is it used

A

used commonly in humans

136
Q

What is a “carrier”

A

a macromolecular substance to which a hapten is coupled in order to produce an immune response against the hapten

137
Q

ERK

A

one of the MAP kinases that activates the transcription factor activation protein 1 (AP-1)

138
Q

Review characteristics of bare lymphocyte disorders

A
139
Q

How are Ig fragments produced

A

Papain cleaves Ig above the hinge, and results in two Fab (antigen-binding) fragments and 1 Fc (crystallizable fragment)

Pepsin cleaves Ig below the hinge at multiple sites

140
Q

How is tolerance maintained to self by the innate immune system

A

this occurs via the dendritic cells. Immature/nonactivated dendritic cells still present self-antigen on their surface. These presentations don’t happen with any costimulation so the T cells don’t get a second signal, which results in continued tolerance.

141
Q

Review the MHC class I antigen-processing pathway

A
142
Q

What is another name for MHC molecules

A

human leukocyte antigens (HLA)

143
Q

For the Xp22 gene, name the associated protein, the protein function, and relevance in atopy

A

TLR 7 and TLR 8, pattern recognition receptor for viral ssRNA, increased risk of asthma/rhinitis/atopic derm and increased specific IgE

144
Q

What are the two main factors that determine T cell tolerance or negative selection in the thymus

A

antigen concentration and antigen affinity to the TCR

high concentration and high affinity promote negative selection

145
Q

What antibody type fixes complement the best

A

IgM

146
Q

At the molecular level, where do superantigens bind the T cell

A

Superantigens bind the variable portion of the Beta chain of TCR (CDR4) that are outside of the peptide-binding groove on the MHC molecule

147
Q

What is a conjugated vaccine

What are some examples

A

T-independent antigens linked to a carrier protein, which can trigger T-dependent response and memory.

Examples are 13-valent pneumococcal vaccine (Prevnar 13), Hib vaccine, and meningococcal vaccines (MCV4-Menactra and Menveo)

148
Q

IRAK4

A

activates NFkB, recurrent pneumococcal disease, think severe pneumococcal infections without fever

MYd88 is similar

149
Q

anhidrotic ectodermal dysplasia is associated with what mutation

A

NEMO

150
Q

Review 95% PPV for failed food challenge (its actually 75% for soy and wheat)

A
151
Q

Continued - review 95% PPV for failed food challenge (its actually 75% for soy and wheat)

A
152
Q

What INS is best studied/safest in pregnancy

A

Rhinocort (Budesonide)

Fluticasone is ok, too

ACAAI Review for the Allergy/Immunology Boards (11 decks)

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