Nature of Antigens and the Major Histocompatibility Complex Flashcards
(170 cards)
1
Q
Immune system that is characterized by specific recognition of individual pathogens
A
Adaptive Immune System
2
Q
The key cells that are responsible for the specificity, diversity, and memory that characterize adaptive immunity
A
Lymphocytes
3
Q
Materials that trigger the immune response of lymphocytes
A
Immunogens
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
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
6
Q
All immunogens are antigens, but the converse is not true. True or False?
A
True
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
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
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
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
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
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
13
Q
Different routes of inoculation
A
Intravenous (into a vein)
Intradermal (into the skin)
Subcutaneous (beneath the skin)
Oral contact
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
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)
16
Q
The ability of an immunogen to stimulate a host response
A
Immunogenicity
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
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
19
Q
“The greater the molecular weight, the more potent the molecule is as an immunogen”. True or False?
A
True
20
Q
How does lymphocytes acquire their ability to distinguish between self and nonself?
A
Thru maturity in primary lymphoid organs
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
22
Q
The most effective immunogens
A
Proteins and polysaccharides
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
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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Why carbohydrates are less immunogenic than proteins?
Because they are smaller than proteins and have a limited number of sugars available to create their structures
26
As immunogens, carbohydrates most often occur in the form of
Glycolipids or Glycoproteins
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Does pure nucleic acids and lipids perform as immunogens?
No; unless attached to suitable carrier molecule
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If a macromolecule cannot be degraded and presented with MHC molecules, then it would be an excellent immunogen. True or False?
False; poor immunogen
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The key portion of the immunogen
Determinant site or epitope
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Molecular shapes or configurations that are recognized by B or T cells
Epitopes
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Number of amino acids in protein epitopes recognized by B cells
As few as 6 to 15 amino acids
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This type of epitope consists of amino acids following one another on a single chain
Sequential/Linear epitopes
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Type of epitope that results from the folding of one chain or multiple chains
Conformational epitope
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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
Conformational epitope
35
Epitopes recognized by B cells may differ from those recognized by T cells. True or False?
True
36
Characteristics of B cells in the recognition of immunogens:
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.
37
How does T cells recognize immunogens?
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
38
Nonimmunogenic materials that, when combined with a carrier, create new antigenic determinants
Haptens
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Haptens by themselves are considered:
Antigen but not immunogen
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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?
True
41
Are haptens capable enough to facilitate precipitation or agglutination? Why?
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.
42
Hapten produced by poison ivy
Catechols
43
How does poison ivy give rise to contact dermatitis?
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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The best known drug (haptens) that combines with normal proteins in the body to provoke an immune response
Penicillin
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Australian scientist who conducted the most famous study of haptens
Karl Landsteiner
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This book provides detailed results of an exhaustive study of haptens; which contributed greatly to our knowledge of antigen–antibody reactions
The Specificity of Serological Reactions, published in 1917
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A substance administered with an immunogen that increases the immune response in order to provide immunity to a particular disease
Adjuvants
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Clinical function of adjuvants
Addition of an adjuvant to a substance used for an immunization helps to make the immunization more effective
49
How does adjuvants work?
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
50
The only adjuvant approved for clinical use
Aluminum salts
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How does aluminum salts perform as adjuvants?
They complex with the immunogen to increase its size and to prevent a rapid escape from the tissues
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Ideal route of inoculation for adjuvants to work
Intramuscular
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Advantage of incorporating adjuvants in immunization:
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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Categories according to their relationship to the host
Autoantigens
Alloantigens
Heteroantigens
Heterophile antigens
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Antigens that belong to the host
Autoantigens
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Characteristics of autoantigens
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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Antigens from other members of the host’s species and are capable of eliciting an immune response
Alloantigens
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Type of antigen in concern in tissue transplantation and in blood transfusions
Alloantigens
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Antigens from other species, such as other animals, plants, or microorganisms
Heteroantigens
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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
Heterophile antigens
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Screening test for Infectious Mononucleosis (IM)
Paul-Bunnell screening test
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Principle of Paul-Bunnell test
Detection of heterophile antibody
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This account for differences in how individuals respond to particular immunogens
Major Histocompatibility Complex
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The genetic capability to mount an immune response is linked to a group of molecules originally referred to as
Human leukocyte antigens (HLA)
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Etiology of the term human leukocyte antigens (HLA)
They were first defined by discovering an antibody response to circulating white blood cells (WBCs)
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Human leukocyte antigens (HLA) are now known as:
Major Histocompatibility Complex (MHC) Molecules
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Etiology of the term MHC molecules
They determine whether transplanted tissue is histocompatible and thus accepted or recognized as foreign and rejected
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MHC molecules are found in:
All nucleated cells in the body
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The main function of MHC
To bring antigen in the body to the surface of cells for recognition by T cells
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When does T-cell activation occur?
T-cell activation will occur only when antigen is combined with MHC molecules on the surface of other cells
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System of genes that encodes cell-surface molecules
MHC
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MHC molecules play a pivotal role in the development of cellular immunity only. True or False?
False; both humoral and cellular immunity
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The most polymorphic system found in humans
MHC system
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Genes that code for proteins that play a pivotal role in immune recognition
MHC genes
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Importance of the polymorphism of MHC system
It is essential to our survival because it allows for an immune response to diverse immunogens
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Location of the genes coding for the MHC molecules in humans
Short arm of chromosome 6
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3 categories/classes of MHC genes:
Class I genes
Class II genes
Class III genes
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Three different locations or loci where class I genes are found:
A, B, C
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Class II genes are situated in what region?
D region
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Different loci where class II genes are found:
DR, DQ, DP
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How many genes are coding for class I molecules?
For class I molecules, there is only one gene coding for each particular molecule
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How many genes are coding for class II molecules?
Class II molecules have one gene that codes for the α chain and one or more genes that code for the β chain
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Location of class III genes
Class III genes lies between the class I and class II regions on chromosome 6
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Proteins coded by class III genes:
C4A
C4B
C2
B complement proteins
Cytokines such as tumor necrosis factor (TNF)
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Function of class I and II molecules
They are involved in antigen recognition; in this role, they influence the repertoire of antigens to which T cells can respond
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Function of class III molecules
They are secreted proteins that have an immune function, but they are not expressed on cell surfaces
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Alternate forms of a gene that code for slightly different varieties of the same product
Alleles
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Why do we describe MHC system as polymorphic?
Because there are so many possible alleles at each location
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When all alleles that an individual inherits code for products that are expressed on cells
Codominant
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Because the MHC genes are closely linked, they are inherited together as a package called a:
Haplotype
91
This accounts for the uniqueness of an individuals MHC type.
Polymorphism; there are numerous alleles or variant forms at each locus
92
How do we serologically define HLA nomenclature?
Through the use of a battery of antibodies
93
Where can we find class I MHC (HLA) molecules?
They are expressed on all nucleated cells
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Where can we find class II MHC (HLA) molecules?
They are found primarily on APCs
95
Body distribution and concentration of class I MHC molecules
Highest:
Lymphocytes
Myeloid cells
Low or undetected:
Liver hepatocytes
Neural cells
Muscle cells
Sperm
96
HLA-C antigens are expressed at a much higher level than HLA-A and HLA-B antigens. True or False?
False, lower levels
97
Clinical correlation of the concentration of HLA-A, HLA-B, HLA-C antigens
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
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Chemical and structural composition of class I antigen
Class I antigen is a glycoprotein dimer made up of two noncovalently linked polypeptide chains (α chain; β2–microglobulin)
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Gene coding for β2–microglobulin of class I MHC
Single gene on chromosome 15 that is not polymorphic
100
What do we mean by “β2–microglobulin is encoded by a single gene on chromosome 15 that is not polymorphic”?
This means that every class I molecule contains the same β2–microglobulin
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Describe the sructure of the α chain of class I antigen
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
Describe the structure and function of β2–microglobulin
β2–microglobulin does not penetrate the cell membrane, but it is essential for proper folding of the α chain
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Function of α1 and α2 domains
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
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Holding capacity of the peptide-binding site of class I MHC
This binding site is able to hold peptides that are between 8 and 11 amino acids long
105
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?
True
106
In class I MHC, the CD8 on cytotoxic T cells reacts with:
α3 region
107
Designation for nonclassical class I antigens
E, F, and G
108
Function of nonclassical class I antigens
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
Function of G antigens
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
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How does G antigens ensure the tolerance of fetus from the action of NK cells?
G antigens bind to NK inhibitory receptors and turn off the NK cytotoxic response
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Function of E antigens
Similar role as G antigen
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Function of F antigens
Unknown
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Where can we find class II MHC molecules?
They are found on the APCs that include:
B lymphocytes
Monocytes
Macrophages
Dendritic cells
Thymic epithelium
114
Most effective antigen-presenting cell
Dendritic cells
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Cells with the highest levels of class II molecules on their surface
Dendritic cells
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Chemical and structural composition of the major class II molecules —DP, DQ, and DR
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
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Class II MCH molecule with the highest level of expression. Why?
DR is expressed at the highest level because it accounts for about one-half of all the class II molecules on a particular cell
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Most highly polymorphic class II MHC molecule
DRβ gene
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Class II MCH molecule with the lowest level of expression
DP
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Both the α chain and the β chain of class II MHC are anchored to the cell membrane. True or False?
True
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Each chain of class II MHC has how many domains?
Each chain has two domains
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This forms the peptide-binding site of class II MHC
α1 and β1 domains
123
Why does class II molecules to capture longer peptides than class I molecules?
Because both ends of the peptide-binding cleft are open
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Designation for nonclassical class II genes
DM, DN, and DO
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Function of nonclassical class II genes
Products of these genes play a regulatory role in antigen processing
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Function of DM gene
Helps to load peptides onto class II molecules
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Function of DO gene
Modulates antigen binding
128
Function of DN gene
Unknown
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In class II MHC, the CD4 on helper T cells reacts with:
β2 region
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The main role of the class I and II MHC molecules
Antigen presentation
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Describe antigen presentation
A process by which degraded peptides within cells are transported to the plasma membrane where T cells can then recognize them
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T cells can only “see” and respond to antigens when they are combined with MHC molecules. True or False?
True
133
Function of class I molecules
mainly present peptides synthesized within the cell to CD8 (cytotoxic) T cells
134
Function of class II molecules
Present exogenous antigen to CD4 (helper) T cells
135
Where does the exogenous proteins presented by class II molecules come from?
They are those taken into the cell from the outside and degraded
136
The watchdogs of viral, tumor, and certain parasitic antigens that are synthesized within the cell
Class I molecules
137
They mount immune response to bacterial infections or other pathogens found outside cells
Class II molecules
138
Minimum requirements to trigger T-cell response:
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
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Functional difference/s between class I and II molecules
The mechanisms by which processed antigen is transported to the surface
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It is where class I molecules are synthesized
Rough endoplasmic reticulum
And for a time they remain anchored in the endoplasmic reticulum membrane
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Why is it called endogenous pathway of antigen presentation?
Because antigens that bind to class I proteins are actually synthesized in the same cell as the class I molecules
142
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?
True
143
88-kd membrane-bound molecule in the endoplasmic reticulum
Calnexin
144
Function of calnexin
Keeps the α chain in a partially folded state while it awaits binding to β2–microglobulin
145
What happens when β2–microglobulin binds to α chain of class I MHC?
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
Intracellular peptides/materials processed by class I molecule:
Virus
Tumor
Bacterial antigen
Defective proteins (fail to fold correctly)
147
Enzyme responsible for the digestion of defective intracellular proteins
Proteases
148
Proteases that reside in large cytoplasmic complexes called
Proteasomes
149
What is proteosome?
Packets of enzymes formed into a cylindrical shape through which peptides pass and are cleaved
150
These are responsible for the adenosine triphosphate-dependent transport of peptides suitable for binding to class I molecules
Transporters associated with antigen processing (TAP1 and TAP2)
151
TAP1 and TAP2 are most efficient at transporting peptides that are between
8 to 16 amino acids in size
152
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?
True
153
Explain the exogenous pathway of antigen presentation
Antigen is taken into the cell from the outside by means of either phagocytosis or endocytosis
154
Describe phagocytosis or endocytosis
processes by which cells ingest extracellular molecules by enclosing them in a small portion of the plasma membrane
155
Characteristics of dendritic cells
Most potent activators of T cells, are excellent at capturing and digesting exogenous antigens such as bacteria
156
Hydrolytic enzymes within the endosomes digest antigen into peptides of
13 to 18 amino acids in length
157
It is where class II molecules are synthesized
Endoplasmic reticulum
158
Protein that associates with class II molecules
Invariant chain (Ii)
159
Molecular weight of invariant chain (Ii)
31-kd
160
Function of invariant chain (Ii)
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
Class II molecules must be transported from the endoplasmic reticulum (ER) to an endosomal compartment where they can then bind peptides. True or False?
True
162
The remaining small fragment after the degradation of invariant chain is called
class II invariant chain peptide (CLIP)
163
Why does the binding groove of MHC class II can accommodate more amino acids than the binding groove of MHC class I?
Because in class II molecules, the groove is open on both ends, unlike class I molecules, which have a closed end
164
Responsible for forming a trimolecular complex that occurs between antigen, class II molecule, and an appropriate TCR
Class II molecules
165
Clinical significance of MHC
Testing for MHC antigens has typically been carried out before tissue transplant procedures
166
Why is it important to test for MHC antigens before tissue transplant procedures?
Because both class I and class II molecules can induce a response that leads to graft rejection
167
How does MHC antigens play a role in the development of autoimmune diseases?
Inheritance of certain HLA antigens appears to predispose a person to certain autoimmune diseases
168
A progressive chronic inflammatory disorder affecting the vertebrae of the spine caused by the inheritance of HLA B27
Ankylosing spondylitis
169
Class I and class II molecules determine the types of peptides to which an individual can mount an immune response. True or False?
True
170
HLA that can increase resistance to HIV infection
HLA B8
