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IMMUNOLOGY AND SEROLOGY > Nature of Antigens and the Major Histocompatibility Complex > Flashcards

Nature of Antigens and the Major Histocompatibility Complex Flashcards

1
Q

Immune system that is characterized by specific recognition of individual pathogens

A

Adaptive Immune System

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2
Q

The key cells that are responsible for the specificity, diversity, and memory that characterize adaptive immunity

A

Lymphocytes

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3
Q

Materials that trigger the immune response of lymphocytes

A

Immunogens

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4
Q

Macromolecules capable of triggering an adaptive immune response by inducing the formation of antibodies or sensitized T cells in an immunocompetent host

A

Immunogens

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5
Q

Substance that reacts with an antibody or sensitized T cells but may not be able to evoke an immune response in the first place

A

Antigens

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6
Q

All immunogens are antigens, but the converse is not true. True or False?

A

True

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7
Q

Factors Influencing the Immune Response

A

Unique biological properties of the individual
Nature of the immunogen
Genetic coding of major histocompatibility complex (MHC) molecules
Immunogen processing and presentation

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8
Q

Biological properties of the individual that influence the nature of the immune response

A

Age
Overall health
Dose
Route of inoculation
Genetic capacity

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9
Q

How does age influence immune response?

A

In general, older individuals are more likely to have a decreased response to antigenic stimulation. At the other end of the age scale, neonates do not fully respond to immunogens because their immune systems are not completely developed

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10
Q

How does overall health influence immune response?

A

Individuals who are malnourished, fatigued, or stressed are less likely to mount a successful immune response

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11
Q

How does dose influence immune response?

A

Generally, the larger the amount of an immunogen one is exposed to, the greater the immune response

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12
Q

It determines the actual amount of immunogen needed to generate an immune response

A

How we are exposed to pathogens and where they get into our bodies

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13
Q

Different routes of inoculation

A

Intravenous (into a vein)
Intradermal (into the skin)
Subcutaneous (beneath the skin)
Oral contact

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14
Q

How does route of inoculation influence immune response?

A

The route where the immunogen enters the body determines which cell populations will be involved in the response

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15
Q

A system of genes that code for cell-surface molecules that play an important role in antigen recognition

A

Major histocompatibility complex (MHC)

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16
Q

The ability of an immunogen to stimulate a host response

A

Immunogenicity

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17
Q

Factors influencing the immunogenicity of immunogens

A

Macromolecular size
Foreignness
Chemical composition and molecular complexity
Ability to be processed and presented with MHC molecules

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18
Q

Usually, an immunogen must have a molecular weight of at least _____ to be recognized by the immune system and the most active immunogens typically have a molecular weight of over _____ daltons

A

10,000; 100,000

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19
Q

“The greater the molecular weight, the more potent the molecule is as an immunogen”. True or False?

A

True

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20
Q

How does lymphocytes acquire their ability to distinguish between self and nonself?

A

Thru maturity in primary lymphoid organs

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21
Q

“The more distant taxonomically the source of the immunogen is from the host, the more successful it is as a stimulus”. True or False?

A

True; more foreign, more effective as immunogen

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22
Q

The most effective immunogens

A

Proteins and polysaccharides

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23
Q

Why do we consider proteins as powerful immunogens?

A

Because they are made up of a variety of units known as amino acids

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24
Q

Nonimmunogenic synthetic polymers made up of a few simple repeating units with no bending or folding within the molecule

A

Nylon or Teflon

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25
Q

Why carbohydrates are less immunogenic than proteins?

A

Because they are smaller than proteins and have a limited number of sugars available to create their structures

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26
Q

As immunogens, carbohydrates most often occur in the form of

A

Glycolipids or Glycoproteins

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27
Q

Does pure nucleic acids and lipids perform as immunogens?

A

No; unless attached to suitable carrier molecule

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28
Q

If a macromolecule cannot be degraded and presented with MHC molecules, then it would be an excellent immunogen. True or False?

A

False; poor immunogen

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29
Q

The key portion of the immunogen

A

Determinant site or epitope

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30
Q

Molecular shapes or configurations that are recognized by B or T cells

A

Epitopes

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31
Q

Number of amino acids in protein epitopes recognized by B cells

A

As few as 6 to 15 amino acids

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32
Q

This type of epitope consists of amino acids following one another on a single chain

A

Sequential/Linear epitopes

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33
Q

Type of epitope that results from the folding of one chain or multiple chains

A

Conformational epitope

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34
Q

This type of epitope brings certain amino acids from different segments of a linear sequence or sequences into close proximity with each other so they can be recognized together

A

Conformational epitope

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35
Q

Epitopes recognized by B cells may differ from those recognized by T cells. True or False?

A

True

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36
Q

Characteristics of B cells in the recognition of immunogens:

A

Reacts with both linear and conformational epitopes of immunogens

Anything that is capable of cross-linking surface immunoglobulin molecules is able to trigger B-cell activation

The immunogen does not necessarily have to be degraded first.

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37
Q

How does T cells recognize immunogens?

A

For T cells to be able to recognize an immunogen it must first be degraded into small peptides by an antigen-presenting cell (APC). Then the peptides form a complex with MHC proteins and are carried to the surface of the APC

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38
Q

Nonimmunogenic materials that, when combined with a carrier, create new antigenic determinants

A

Haptens

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39
Q

Haptens by themselves are considered:

A

Antigen but not immunogen

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40
Q

Once antibody production is initiated, the hapten is capable of reaction with antibody even when the hapten is not complexed to a carrier molecule. True or False?

A

True

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41
Q

Are haptens capable enough to facilitate precipitation or agglutination? Why?

A

Precipitation or agglutination reactions will not occur because a hapten has a single determinant site and cannot form the cross-links with more than one antibody molecule that are necessary for precipitation or agglutination.

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42
Q

Hapten produced by poison ivy

A

Catechols

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43
Q

How does poison ivy give rise to contact dermatitis?

A

Poison ivy (Rhus radicans) contains chemical substances called catechols, which are haptens. Once in contact with the skin, these can couple with tissue proteins to form the immunogens that give rise to contact dermatitis

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44
Q

The best known drug (haptens) that combines with normal proteins in the body to provoke an immune response

A

Penicillin

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45
Q

Australian scientist who conducted the most famous study of haptens

A

Karl Landsteiner

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46
Q

This book provides detailed results of an exhaustive study of haptens; which contributed greatly to our knowledge of antigen–antibody reactions

A

The Specificity of Serological Reactions, published in 1917

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47
Q

A substance administered with an immunogen that increases the immune response in order to provide immunity to a particular disease

A

Adjuvants

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48
Q

Clinical function of adjuvants

A

Addition of an adjuvant to a substance used for an immunization helps to make the immunization more effective

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49
Q

How does adjuvants work?

A

Adjuvants actually work by targeting APCs, which are key to the adaptive immune response. Substances used as adjuvants protect immunogens from degradation and allow a longer response time that attracts a large number of immune system cells to the injection site, which helps to boost the strength of the response

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50
Q

The only adjuvant approved for clinical use

A

Aluminum salts

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51
Q

How does aluminum salts perform as adjuvants?

A

They complex with the immunogen to increase its size and to prevent a rapid escape from the tissues

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52
Q

Ideal route of inoculation for adjuvants to work

A

Intramuscular

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53
Q

Advantage of incorporating adjuvants in immunization:

A

Adjuvants are used to accelerate the immune response and increase the duration of protection, thus reducing the need for booster immunizations

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54
Q

Categories according to their relationship to the host

A

Autoantigens
Alloantigens
Heteroantigens
Heterophile antigens

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55
Q

Antigens that belong to the host

A

Autoantigens

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56
Q

Characteristics of autoantigens

A

Does not evoke immune response under normal circumstances. However, if an immune response does occur to autoantigens, it may result in an autoimmune disease

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57
Q

Antigens from other members of the host’s species and are capable of eliciting an immune response

A

Alloantigens

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58
Q

Type of antigen in concern in tissue transplantation and in blood transfusions

A

Alloantigens

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59
Q

Antigens from other species, such as other animals, plants, or microorganisms

A

Heteroantigens

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60
Q

Heteroantigens that exist in unrelated plants or animals but are either identical or closely related in structure so that antibody to one will cross-react with antigen of the other

A

Heterophile antigens

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61
Q

Screening test for Infectious Mononucleosis (IM)

A

Paul-Bunnell screening test

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62
Q

Principle of Paul-Bunnell test

A

Detection of heterophile antibody

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63
Q

This account for differences in how individuals respond to particular immunogens

A

Major Histocompatibility Complex

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64
Q

The genetic capability to mount an immune response is linked to a group of molecules originally referred to as

A

Human leukocyte antigens (HLA)

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65
Q

Etiology of the term human leukocyte antigens (HLA)

A

They were first defined by discovering an antibody response to circulating white blood cells (WBCs)

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66
Q

Human leukocyte antigens (HLA) are now known as:

A

Major Histocompatibility Complex (MHC) Molecules

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67
Q

Etiology of the term MHC molecules

A

They determine whether transplanted tissue is histocompatible and thus accepted or recognized as foreign and rejected

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68
Q

MHC molecules are found in:

A

All nucleated cells in the body

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69
Q

The main function of MHC

A

To bring antigen in the body to the surface of cells for recognition by T cells

70
Q

When does T-cell activation occur?

A

T-cell activation will occur only when antigen is combined with MHC molecules on the surface of other cells

71
Q

System of genes that encodes cell-surface molecules

A

MHC

72
Q

MHC molecules play a pivotal role in the development of cellular immunity only. True or False?

A

False; both humoral and cellular immunity

73
Q

The most polymorphic system found in humans

A

MHC system

74
Q

Genes that code for proteins that play a pivotal role in immune recognition

A

MHC genes

75
Q

Importance of the polymorphism of MHC system

A

It is essential to our survival because it allows for an immune response to diverse immunogens

76
Q

Location of the genes coding for the MHC molecules in humans

A

Short arm of chromosome 6

77
Q

3 categories/classes of MHC genes:

A

Class I genes
Class II genes
Class III genes

78
Q

Three different locations or loci where class I genes are found:

A

A, B, C

79
Q

Class II genes are situated in what region?

A

D region

80
Q

Different loci where class II genes are found:

A

DR, DQ, DP

81
Q

How many genes are coding for class I molecules?

A

For class I molecules, there is only one gene coding for each particular molecule

82
Q

How many genes are coding for class II molecules?

A

Class II molecules have one gene that codes for the α chain and one or more genes that code for the β chain

83
Q

Location of class III genes

A

Class III genes lies between the class I and class II regions on chromosome 6

84
Q

Proteins coded by class III genes:

A

C4A
C4B
C2
B complement proteins
Cytokines such as tumor necrosis factor (TNF)

85
Q

Function of class I and II molecules

A

They are involved in antigen recognition; in this role, they influence the repertoire of antigens to which T cells can respond

86
Q

Function of class III molecules

A

They are secreted proteins that have an immune function, but they are not expressed on cell surfaces

87
Q

Alternate forms of a gene that code for slightly different varieties of the same product

A

Alleles

88
Q

Why do we describe MHC system as polymorphic?

A

Because there are so many possible alleles at each location

89
Q

When all alleles that an individual inherits code for products that are expressed on cells

A

Codominant

90
Q

Because the MHC genes are closely linked, they are inherited together as a package called a:

A

Haplotype

91
Q

This accounts for the uniqueness of an individuals MHC type.

A

Polymorphism; there are numerous alleles or variant forms at each locus

92
Q

How do we serologically define HLA nomenclature?

A

Through the use of a battery of antibodies

93
Q

Where can we find class I MHC (HLA) molecules?

A

They are expressed on all nucleated cells

94
Q

Where can we find class II MHC (HLA) molecules?

A

They are found primarily on APCs

95
Q

Body distribution and concentration of class I MHC molecules

A

Highest:
Lymphocytes
Myeloid cells

Low or undetected:
Liver hepatocytes
Neural cells
Muscle cells
Sperm

96
Q

HLA-C antigens are expressed at a much higher level than HLA-A and HLA-B antigens. True or False?

A

False, lower levels

97
Q

Clinical correlation of the concentration of HLA-A, HLA-B, HLA-C antigens

A

Since HLA-C is expressed at a much lower level than the other two, HLA-A and HLA-B antigens are the most important to match for transplantation

98
Q

Chemical and structural composition of class I antigen

A

Class I antigen is a glycoprotein dimer made up of two noncovalently linked polypeptide chains (α chain; β2–microglobulin)

99
Q

Gene coding for β2–microglobulin of class I MHC

A

Single gene on chromosome 15 that is not polymorphic

100
Q

What do we mean by “β2–microglobulin is encoded by a single gene on chromosome 15 that is not polymorphic”?

A

This means that every class I molecule contains the same β2–microglobulin

101
Q

Describe the sructure of the α chain of class I antigen

A

The α chain is folded into three domains—α1, α2, and α3—and it is inserted into the cell membrane via a transmembrane segment that is hydrophobic

102
Q

Describe the structure and function of β2–microglobulin

A

β2–microglobulin does not penetrate the cell membrane, but it is essential for proper folding of the α chain

103
Q

Function of α1 and α2 domains

A

They serve as the walls of a deep groove at the top of the molecule that functions as the peptide-binding site in antigen recognition

104
Q

Holding capacity of the peptide-binding site of class I MHC

A

This binding site is able to hold peptides that are between 8 and 11 amino acids long

105
Q

In class I MHC, most of the polymorphism resides in the α1 and α2 regions, whereas the α3 and β2 regions are relatively constant. True or False?

A

True

106
Q

In class I MHC, the CD8 on cytotoxic T cells reacts with:

A

α3 region

107
Q

Designation for nonclassical class I antigens

A

E, F, and G

108
Q

Function of nonclassical class I antigens

A

This group of molecules, except for G, are not expressed on cell surfaces and do not function in antigen recognition but may play other roles in the immune response

109
Q

Function of G antigens

A

Expressed on fetal trophoblast cells during the first trimester of pregnancy. G antigens are thought to help ensure tolerance for the fetus by protecting placental tissue from the action of NK cells

110
Q

How does G antigens ensure the tolerance of fetus from the action of NK cells?

A

G antigens bind to NK inhibitory receptors and turn off the NK cytotoxic response

111
Q

Function of E antigens

A

Similar role as G antigen

112
Q

Function of F antigens

A

Unknown

113
Q

Where can we find class II MHC molecules?

A

They are found on the APCs that include:
B lymphocytes
Monocytes
Macrophages
Dendritic cells
Thymic epithelium

114
Q

Most effective antigen-presenting cell

A

Dendritic cells

115
Q

Cells with the highest levels of class II molecules on their surface

A

Dendritic cells

116
Q

Chemical and structural composition of the major class II molecules —DP, DQ, and DR

A

Consist of two noncovalently bound polypeptide chains that are encoded by separate genes in the MHC complex. These molecules are called heterodimers because they contain two different chains

117
Q

Class II MCH molecule with the highest level of expression. Why?

A

DR is expressed at the highest level because it accounts for about one-half of all the class II molecules on a particular cell

118
Q

Most highly polymorphic class II MHC molecule

A

DRβ gene

119
Q

Class II MCH molecule with the lowest level of expression

A

DP

120
Q

Both the α chain and the β chain of class II MHC are anchored to the cell membrane. True or False?

A

True

121
Q

Each chain of class II MHC has how many domains?

A

Each chain has two domains

122
Q

This forms the peptide-binding site of class II MHC

A

α1 and β1 domains

123
Q

Why does class II molecules to capture longer peptides than class I molecules?

A

Because both ends of the peptide-binding cleft are open

124
Q

Designation for nonclassical class II genes

A

DM, DN, and DO

125
Q

Function of nonclassical class II genes

A

Products of these genes play a regulatory role in antigen processing

126
Q

Function of DM gene

A

Helps to load peptides onto class II molecules

127
Q

Function of DO gene

A

Modulates antigen binding

128
Q

Function of DN gene

A

Unknown

129
Q

In class II MHC, the CD4 on helper T cells reacts with:

A

β2 region

130
Q

The main role of the class I and II MHC molecules

A

Antigen presentation

131
Q

Describe antigen presentation

A

A process by which degraded peptides within cells are transported to the plasma membrane where T cells can then recognize them

132
Q

T cells can only “see” and respond to antigens when they are combined with MHC molecules. True or False?

A

True

133
Q

Function of class I molecules

A

mainly present peptides synthesized within the cell to CD8 (cytotoxic) T cells

134
Q

Function of class II molecules

A

Present exogenous antigen to CD4 (helper) T cells

135
Q

Where does the exogenous proteins presented by class II molecules come from?

A

They are those taken into the cell from the outside and degraded

136
Q

The watchdogs of viral, tumor, and certain parasitic antigens that are synthesized within the cell

A

Class I molecules

137
Q

They mount immune response to bacterial infections or other pathogens found outside cells

A

Class II molecules

138
Q

Minimum requirements to trigger T-cell response:

A

Peptides must be available in adequate supply for MHC molecules to bind
Must be able to be bound effectively
Must be recognized by a TCR

139
Q

Functional difference/s between class I and II molecules

A

The mechanisms by which processed antigen is transported to the surface

140
Q

It is where class I molecules are synthesized

A

Rough endoplasmic reticulum

And for a time they remain anchored in the endoplasmic reticulum membrane

141
Q

Why is it called endogenous pathway of antigen presentation?

A

Because antigens that bind to class I proteins are actually synthesized in the same cell as the class I molecules

142
Q

Binding of the newly synthesized proteins helps to stabilize the association of the α chain of class I with the β2–microglobulin. True or False?

A

True

143
Q

88-kd membrane-bound molecule in the endoplasmic reticulum

A

Calnexin

144
Q

Function of calnexin

A

Keeps the α chain in a partially folded state while it awaits binding to β2–microglobulin

145
Q

What happens when β2–microglobulin binds to α chain of class I MHC?

A

When β2–microglobulin binds, calnexin and ERp57 are released and two other chaperone molecules—calreticulin and tapasin— associate with the complex and help to stabilize it for peptide binding

146
Q

Intracellular peptides/materials processed by class I molecule:

A

Virus
Tumor
Bacterial antigen
Defective proteins (fail to fold correctly)

147
Q

Enzyme responsible for the digestion of defective intracellular proteins

A

Proteases

148
Q

Proteases that reside in large cytoplasmic complexes called

A

Proteasomes

149
Q

What is proteosome?

A

Packets of enzymes formed into a cylindrical shape through which peptides pass and are cleaved

150
Q

These are responsible for the adenosine triphosphate-dependent transport of peptides suitable for binding to class I molecules

A

Transporters associated with antigen processing (TAP1 and TAP2)

151
Q

TAP1 and TAP2 are most efficient at transporting peptides that are between

A

8 to 16 amino acids in size

152
Q

Of the thousands of peptides that may be processed by class I MHC, only a small fraction of them (1% or less) actually induce a T-cell response. True or False?

A

True

153
Q

Explain the exogenous pathway of antigen presentation

A

Antigen is taken into the cell from the outside by means of either phagocytosis or endocytosis

154
Q

Describe phagocytosis or endocytosis

A

processes by which cells ingest extracellular molecules by enclosing them in a small portion of the plasma membrane

155
Q

Characteristics of dendritic cells

A

Most potent activators of T cells, are excellent at capturing and digesting exogenous antigens such as bacteria

156
Q

Hydrolytic enzymes within the endosomes digest antigen into peptides of

A

13 to 18 amino acids in length

157
Q

It is where class II molecules are synthesized

A

Endoplasmic reticulum

158
Q

Protein that associates with class II molecules

A

Invariant chain (Ii)

159
Q

Molecular weight of invariant chain (Ii)

A

31-kd

160
Q

Function of invariant chain (Ii)

A

Ii may be responsible for helping to bring α and β chains together in the ER lumen and then moving them out through the Golgi complex to the endocytic vesicles where digested antigen is found

161
Q

Class II molecules must be transported from the endoplasmic reticulum (ER) to an endosomal compartment where they can then bind peptides. True or False?

A

True

162
Q

The remaining small fragment after the degradation of invariant chain is called

A

class II invariant chain peptide (CLIP)

163
Q

Why does the binding groove of MHC class II can accommodate more amino acids than the binding groove of MHC class I?

A

Because in class II molecules, the groove is open on both ends, unlike class I molecules, which have a closed end

164
Q

Responsible for forming a trimolecular complex that occurs between antigen, class II molecule, and an appropriate TCR

A

Class II molecules

165
Q

Clinical significance of MHC

A

Testing for MHC antigens has typically been carried out before tissue transplant procedures

166
Q

Why is it important to test for MHC antigens before tissue transplant procedures?

A

Because both class I and class II molecules can induce a response that leads to graft rejection

167
Q

How does MHC antigens play a role in the development of autoimmune diseases?

A

Inheritance of certain HLA antigens appears to predispose a person to certain autoimmune diseases

168
Q

A progressive chronic inflammatory disorder affecting the vertebrae of the spine caused by the inheritance of HLA B27

A

Ankylosing spondylitis

169
Q

Class I and class II molecules determine the types of peptides to which an individual can mount an immune response. True or False?

A

True

170
Q

HLA that can increase resistance to HIV infection

A

HLA B8

IMMUNOLOGY AND SEROLOGY (3 decks)

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