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Clinical Chemistry 2 > Major Histocompatibility Complex > Flashcards

Major Histocompatibility Complex Flashcards

Summa CUM laude.

1
Q

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**Enumerate: **Functions of T lymphocytes

A
  • Defense against cell-associated microbes
  • Inhibition of immune responses
  • T cell functions require cell-cell interactions or cytokines that act at short range
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2
Q

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Regulatory T cells suppress APCs or other lymphocytes is what function of T-lymphocyte

A

Inhibition of immune responses

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3
Q

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What function of T-lymphocyte:
Phagocyting and killing infected cells and eliminate reservoirs of infection”

A

Defense against cell-associated microbes

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4
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Identify: helps phagocytes to kill ingested microbes and help B cells to make potent antibodies

A

Helper T cells

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5
Q

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kills infected cells and eliminate reservoirs of infection

A

Cytotoxic T lymphocytes (CTLs)

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6
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Enumerate challenges for T lymphocytes

A
  • Very few lymphocytes in the body are specific for any one microbe (or antigen)
  • Lymphocytes must be able to locate and respond to microbes that enter and reside anywhere in the body
  • Lymphocytes must respond to each microbe in ways that are best able to eradicate that microbe
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7
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Specificity and diversity of antigen receptors:

A

–the immune system recognizes and distinguishes between 106 - 109 antigens; the body contains ~ 1012 lymphocytes; therefore, few lymphocytes (~1,000) can recognize any one antigen and need to find that antigen

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8
Q

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Response to extracellular microbes?

A

antibodies that promote phagocytosis; destruction in macrophages (need helper T cells)

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9
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Response to intracellular microbes?

A

killing of infected cells (need CTLs)

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10
Q

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Sites of Antigen entry

A

Skin

GIT

Respiratory tract

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11
Q

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Sites of Initial Antigen capture

A

Lymphatic system

Peripheral blood circulation

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12
Q

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Sites of antigen collection and capture

A

Lymph node

Spleen

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13
Q

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Sites of microbe entry

A

skin, GI tract, airways

(organs with continuous

epithelia, populated

with dendritic cells).

Less often – colonized

tissues, blood

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14
Q

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Sites of lymphocyte activation:

A

peripheral

lymphoid organs (lymph

nodes, spleen), mucosal

and cutaneous lymphoid

tissues)

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15
Q

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Antigens and naïve T cells come together in ???

A

lymphoid organs

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16
Q

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Why are dendritic cells the most efficient APCs for initiating immune responses?

A
  • Location
  • Receptors for capturing and reacting to microbes:T
  • Migration to T cell zones of lymphoid organs
  • Maturation during migration
  • Practical application
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17
Q

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What do T cells see?

A
  • All functions of T cells are mediated by interactions with other cells
  • To ensure cellular communications, T cells see antigens NOT in the circulation but only when displayed by molecules on the surface of other cells
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18
Q

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cells displaying the antigen are called

A

APCs - Antigen Presenting Cells

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19
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Explain:

A

During their maturation in the thymus, T cells whose TCRs see MHC molecules are selected to mature, i.e. mature T cells are MHC-restricted

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20
Q

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True or False: Mature B cells are MHC-restricted.

A

False.

During their maturation in the thymus, T cells whose TCRs see MHC molecules are selected to mature, i.e. **mature T cells are MHC-restricted **

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21
Q

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A genetic locus discovered on the basis of transplantation

A

Major histocompatibility complex

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22
Q

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Human MHC

A

HLA (human leukocyte antigens)

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23
Q

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Determine how antigens in different cellular compartments are recognized by different classes of T cells (CD4+ and CD8+)

A

MHC molecules

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24
Q

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Determines which protein antigens are recognized in different individuals

A

MHC

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25
Q

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True of False: MHC genes are highly polychromic.

A

Negative

MHC genes are highly polymorphic; the MHC molecules in the population can display many different peptides

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26
Q

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What are the antigen receptors of T cells that gives it dual specificities

A
  1. for peptide antigen (responsible for specificity of immune response)
  2. for MHC molecules (responsible for MHC restriction)
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27
Q

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WHO first defined by discovering an ab response to circulating WBCs (HLA)

A

Jean Dausset

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28
Q

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MHC is relevant in what clinical situations/conditions

A

•transfusion reactions, graft rejections, and autoimmune diseases

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29
Q

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True or False: MHC is Plays a role in humoral immunity

A

Negative

MHC plays a role in both cellular and humoral immunity

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30
Q

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True of False:
MHC is found on all nucleated cells

A

TRUE

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31
Q

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Explain Classes of MHC genes.

A

A, B, C loci = class I

D locus = class II

Class III= in between class I and II, codes for complement, cytokine (TNF)

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32
Q

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State the Possible alleles of ALL MHC genes

A

HLA-A = 580 possible alleles

HLA-B = 921 possible alleles

HLA-C = 312 possible alleles

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33
Q

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Crossover rate of MHC genes

A

0.5% crossover rate

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34
Q

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Refers to sets inherited from mother or father

A

Haplotype

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35
Q

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True of False: MHC Alleles Are Sex-linked dominantly Expressed

A

Negative

MHC Alleles Are Co-dominantly Expressed
–Both mother and father alleles are expressed

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36
Q

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Counterpart of the MHC in mouse/mice/rats/rodents/shits

A

H-2

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37
Q
A

Centromere= left side, Telomere= right side

Class I MHC locus (A,B,C)-found on telomere

Class II MHC locus [DP, DM, DQ, DR, Proteasome genes (TAP 1,2 )] - found on centromere

Class III MHC locus [Complement proteins (C4, Factor B, C2), Cytokines (lymphotoxin beta, TNF-alpha, LT) - In between

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38
Q
A

Structure of MHC Class I

  • Glycoprotein dimer
  • Alpha chain = 45 000 MW; folded into three domains (α1, α2, α3)
  • α1, α2, α3 consists of 90 aa each
  • transmembrane domain consists of 25 hydrophobic aa plus a short stretch of 5 hydrophilic aa and an anchor or 30 aa

•Β2 microglobulin = 12 000 MW: does not penetrate the cell membrane, but is essential for proper folding the alpha chain

Ag binding cleft : hold peptides that are between 8-10 amino acids long

Alpha3: reacts with cytotoxic T cells

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39
Q

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Two most important to match for transplantation

A

HLA-A and HLA-B expressed at higher levels than HLA-C : two most important to match for transplantation

40
Q

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T or F: Class I is expressed on all nucleated cells

41
Q

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Class I is highly expressed on ____ and low or undetected in ___

A

•Highest expression on lymphocytes** and low or undetected on **liver hepatocytes, neural cells, muscle cell and sperm

42
Q

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Designated as E,F,G

A

Non-classical Class I Antigens

43
Q

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Expressed on trophoblast cells during the first trimester of pregnancy and help ensure tolerance for the fetus by protecting placental tissue from the action of NK cells

A

G non-classical Class I Antigen

44
Q

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Do not function in antigen recognition but play a role in the immune response

A

Non-classical Class I antigen

45
Q

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Non-classical Class I antigens expressed on the surface of cells

46
Q

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T or : Class I is more restricted than Class II antigens

47
Q

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Found on Ag-presenting cells (monocytes, macrophages, dendritic cells) and B lymphocytes

48
Q

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Class II gene expressed at the highest level

49
Q

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Major class II genes

A

DP, DQ, DR

50
Q

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Most polymorphic Class II gene

A

DRβ has 18 possible alleles, therefore most polymorphic

51
Q

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Peptide binding site of Class II

A

α1 and β1

52
Q

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Class II structure

A
  • Has α chain = 33 000 MW and β chain = 27 000 MW
  • Both are anchored to the cell membrane
  • Each has 2 domains
53
Q

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Binding site for the CD4.
(Class II Ag)

A

b2 is the binding site for the CD4.

54
Q

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The a and b chains of the Class II Ag

A

.
•The a chains are the HLA DR
•The b chains are the HLA DQ and DP

55
Q

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Products of these genes play a regulatory role in antigen processing

A

Non-classical Class II

56
Q

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Non-classical Class II genes

A

DM, DN, DO

57
Q

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Location of polymorphic residues of Class I

A

a-1 and a-2 domains

58
Q

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Location of polymorphic residues of Class II

A

a-1 and b-1 domains

59
Q

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Class I MHC nomenclature for mouse

A

H-2K, H-2K, H-2L

60
Q

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Class II nomenlature for mouse

61
Q

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Size of peptide-binding cleft of Class I MHC

A

Accomodates peptides of 8-11 residues

62
Q

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Size of peptide-binding cleft of Class II MHC

A

Accomodates peptides of 10-30 residues or more

63
Q

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Binding site for T cell coreceptor of Class I MHC

A

a3 region binds CD8

64
Q

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Binding site for T cell coreceptor of Class II MHC

A

B2 binds CD4

65
Q

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Polypeptide chains of Class I MHC

A

a (44-47 kD)

b2-microglobulin (12 kD)

66
Q

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Polypeptide chains of Class II MHC

A

a (32-34 kD)

B (29-32 kD)

67
Q

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Conversion of native antigen (large globular protein) into peptides capable of binding to MHC molecules

A

Antigen processing

68
Q

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Where does antigen processing occur?

A

Occurs in cellular compartments where MHC molecules are synthesized and assembled

–Determines how antigen in different cellular compartments generates peptides that are displayed by class I or class II MHC molecules

69
Q

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stimulates T helper cell in the case of bacterial infections

70
Q

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bind exogenous protein and present it to CD4 T cells

71
Q

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watchdogs of viral, tumor & certain parasitic Ags that are synthesized w/in the cell (endogenous Ags)

72
Q

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present peptides that have been synthesized within the cell to CD8 T cells

73
Q

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Class I MHC pathway

A

Protein antigen in cytosol (cytoplasm)

74
Q

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Class II MHC pathway

A

Protein antigen in vesicles

75
Q

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must be transported from ER to an endosomal compartment before they can bind peptides

76
Q

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bind peptides while still in the ER

binding stabilize association of α with β2 microglobulin

77
Q

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Both Class I and II molecules are synthesized in the ___ and for a time anchored in the ____

A

Both Class I and II molecules are synthesized in the RER, and for a time anchored in the ER

78
Q

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88 kd molecule, membrane bound in the ER, keeps the α chain partially folded while it awaits binding to β2 microglobulin, once β2 microglobulin binds it is released , and other chaperone molecules (calreticulin, tapason, and ERp57) are associated w/complex and help to stabilize it for the peptide binding

79
Q

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Pathways of antigen processing

A
  1. Antigen uptake
  2. Antigen processing
  3. MHC biosynthesis
  4. Peptide-MHC association
80
Q

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Explain: The class I MHC pathway of processing of endogenous cytosolic protein antigens

A
  1. Production of proteins in the cytosol
  2. Proteolytic degradation of proteins
  3. Transport of peptides from cytosol to the ER
  4. Assembly of peptide-class I complexes in the ER
  5. Surface expression of peptide-class I complexes
81
Q

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Defective ribosomal products, peptides that fail to correctly fold and hence defective, about 20-70percent of all proteins synthesized by the cell, must be digested by the proteases (by proteasome)

82
Q

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Peptides derived from proteins found in the cytosol that are then degraded by the multiproteolytic _________complex into peptides. (Class I pathway)

A

Proteasome

83
Q

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Brings the TAP transporters into close proximity to the newly formed MHC molecules and mediates interaction with them so that the peptides can be loaded to MHC class I

84
Q

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are cooperatively folded into the newly synthesized MHC-I molecule.

A

transporter associated with antigen processing (TAP)

85
Q

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The first step in the activation of a CD8+ cellular program

A

The MHC-I molecule allows the APC bearing a particular MHC–peptide complex to **engage an appropriate alpha beta T cell receptor **

86
Q

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The activation of a CD8+ cellular program that might lead to ________________________.

A

cytolysis of the APC as a target and/or to the **secretion of lymphokines by the T cell. **

87
Q

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The class II MHC pathway of processing of internalized vesicular protein antigens

A
  1. Uptake of extracellular proteins into vesicular compartments of APC
  2. Processing of internalized proteins in endosomal/lysosomal vesicles
  3. Biosynthesis and transport of Class II MHC molecules to endosomes
  4. Association of processed peptides with with Class II MHC molecules in vesicles
  5. Expression of peptide-MHC molecule on cell surface
88
Q

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31 kd protein that is made in excess to make sure all Class I molecules have Ii, prevents interaction of Class II binding site to the endogenous proteins of ER, helps to bring α and β chains together in the ER lumen and then moving them thru the golgi apparatus to the endocytic vesicles where digested Ag is found

A

Invariant chain

89
Q

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serves as a chaperone to direct the ab heterodimer to an endosomal, acidic protein–processing location.

A

invariant chain (Ii)

90
Q

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Help to mediate the reaction by removing the CLIP fragment

91
Q

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Class II invariant chain peptide, attached to the peptide-binding cleft

92
Q

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inside-out pathway

93
Q

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outside-in pathway

94
Q

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How does class I-associated antigen presentation

influence the nature of the host T cell response/Activation of a CD4+ cellular program might lead to

A

Macrophage activation: destruction of phagocytosed antigen

B cell antibody secretion: antibody binding to antigen

95
Q

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How class II-associated antigen presentation

influence the nature of the host T cell response

A

Killing of antigen-expressing taget cell

96
Q

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Association of Human MHC Alleles and Risk for Diseases

A

Disease Associated HLA Allele Relative Risk**

Ankylosing Spondylitis* B27 90

Hereditary Hemochromatosis A3/B14 90

Insulin Dependent Diabetes* DR4/DR3 20

Multiple Sclerosis* DR2 5

Myasthenia Gravis* DR3 10

Rheumatoid Arthritis* DR4 10

Systemic Lupus Erythromatosis* DR3 5

* Autoimmune Disease **Percent of Patients with Allele Divided by Percent of Non-Affected Persons with this Allele

•

Narcolepsy DR2 130

97
Q

Clinical Chemistry 2 (11 decks)

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