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MICRO > Ch3: Lymph, MHC, Antigen Presentation > Flashcards

Ch3: Lymph, MHC, Antigen Presentation Flashcards

1
Q

What are the five steps of the immune response in the transition from innate to adaptive immunity?

A
  1. Adherence to epithelium
  2. Penetration of epithelium
  3. Local infection of tissues
  4. Lymphatic spread
  5. Adaptive immunity begins
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2
Q

How does the immune system protect against bacterial adherence?

A

Normal flora and chemical factors

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3
Q

How does the immune system protect against penetration?

A

Anti-microbial proteins, peptides, phagocytes and complement destroy invaders

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4
Q

How does the immune system protect against local infection in tissues?

A
  1. Complement activation
  2. Dendritic cells migrate to lymph nodes
  3. NK Cells activated
  4. Cytokines and chemokines produced
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5
Q

How does the immune system use lymphatic spread?

A

Pathogens trapped and phagocytosed in lymphoid tissue which allows dendritic cells to initiate adaptive immunity

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6
Q

What happens in adaptive immunity?

A

Infection clared by specific antibody, T-cell dependent macrophage activation and cytotoxic T cells

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7
Q

What are the two primary lymphoid organs?

A

Thymus and Bone Marrow

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8
Q

What are some of the secondary lymphoid organs? 6

A
  1. Adenoid
  2. Tonsil
  3. Thoracic Duct
  4. Spleen
  5. Peyer’s patches
  6. Appendix
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9
Q

What lymph nodes drain the upper limb and lateral breast?

A

Axillary

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10
Q

What lymph nodes drain the stomach?

A

Celiac

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11
Q

What lymph nodes drain the duodenum and jejunum?

A

Superior mesenteric

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12
Q

What lymph nodes drain the sigmoid colon?

A

Colic –> inferior mesenteric

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13
Q

What lymph nodes drain the rectum and anal canal above pectinate line?

A

Internal iliac

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14
Q

What lymph nodes drain the anal canal below pectinate line, scrotum, and superficial thigh?

A

Superficial inguinal

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15
Q

What lymph nodes drain the testes?

A

Superficial and deep plexuses

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16
Q

What lymph nodes drain the lateral side of dorsum of foot?

A

Popliteal

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17
Q

Are lymphocytes mature upon leaving circulation for lymph nodes ?

A

Yes, but naive.

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18
Q

What happens if lymphocyte encounters their specific antigen?

A

Lymphocyte activates, differentiates, and clears the pathogen

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19
Q

What happens if lymphocyte does not encounter antigen? 4

A
  1. Leave lymph node via efferent lymphatic vessel.
  2. Reside in lymph
  3. Return to blood via thoracic duct
  4. Enter lymph node
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20
Q

How is the antigen transported to the lymph node?

A
  1. Antigen presenting cell finds antigen and travels via lymph vessel to the lymph nodes
  2. The spleen looks through the blood for antigens
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21
Q

Activated dendritic cells move to lymph node to do what?

A

Activate B cells and T cells

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22
Q

Upon activation, T and B cells go where?

A

To site of infection to remove pathogen

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23
Q

How do naive lymphocytes enter lymph nodes?

A

Capillaries/High endothelial venules

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24
Q

How do pathogen-loaded dendritic cells enter lymph nodes?

A

Afferent lymphatic vessels

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25
Q

If naive lymphocytes recognize the pathogen carried by DC, what happens?

A
  1. Activate
  2. Differentiate into effector cells
  3. Leave via efferent lymphatic vessel
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26
Q

What are germinal centers?

What controls them?

A

Sites of B cell proliferation

T-cells

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27
Q

What type of lymphatic vessels drain tissue?

What do they carry? (2)

A

Afferent

Pathogens and APC’s

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28
Q

What delivers lymphocytes from bloodstream to node?

A

High endothelial venules

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29
Q

Where are B cells found?

A

Follicles of lymph node

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30
Q

Where are T cells found?

A

Paracortical area of lymph node

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31
Q

3 differences between spleen and lymph node

A
  1. Removes dead red blood cells in the red pulp area
  2. White blood cells are present in white pulp
  3. Spleen does not drain lymph, it drains whole blood
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32
Q

Germinal centers in the spleen form along what?

A

Periarteriolar lymphoid sheath (PALS)

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33
Q

Marginal zone B cells in spleen produce what?

A

IgM

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34
Q

Does the spleen have a direction link to lymphatics?

A

No

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35
Q

What type of cells form the PALS?

A

T cells

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36
Q

Marginal zone around spleen follicle contains what cells mainly? 2

A
  1. Macrophages

2. Non-circulating marginal zone B cells

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37
Q

What covers Peyer’s patches?

A

Epithelial layer containing M cells

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38
Q

Gut-associated lymphoid tissue (GALT) is found where? (4)

A
  1. Tonsils
  2. Adenoids
  3. Appendix
  4. Peyers Patches
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39
Q

What cell collects antigen from epithelial surface in GALT?

A

M cells

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40
Q

What forms the Peyer’s patch?

A

Central dome of B cells surrounded by T Cells

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41
Q

What is the main function of Peyer’s patch

A

Local response to pathogens without draining to a lymph node

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42
Q

The major histocmpatability complex has its gene locus where?

How many BP’s?

How many genes?

A

Chromosome 6

4,000,000 BP’s

200 genes

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43
Q

What are the two main groups of proteins that present antigen to T cells?

A

MHC Class I

MHC Class II

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44
Q

What does HLA stand for?

A

Human leukocyte antigen

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45
Q

What domains make up the Class I peptide binding cleft?

A

Alpha1 and alpha2

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46
Q

What domains make up the Class II peptide binding cleft?

A

Alpha1 and Beta1

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47
Q

What cells express MHC I?

A

All nucleated cells

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48
Q

What cells express MHC II?

A

Professional antigen presenting cells?

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49
Q

3 types of progessional antigen presenting cells?

A

Dendritic cells
B cells
Macrophages

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50
Q

What is special about the expression of MHC genes? 2

A
  1. Co-dominant expression so both parental alleles are expressed giving you more MHC varieties
  2. Polymorphic genes: Many different alleles
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51
Q

What type of cells interact with MHC Class II cells?

A

CD4+ Helper T cells

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52
Q

What type of cells interact with MHC Class I cells?

A

CD8+ Cytotoxic T Cells

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53
Q

The dendritic cell is located where in lymph node?

A

T-Cell areas

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54
Q

How does the dendritic cell uptake the antigen? 3

A
  1. Macropinocytosis
  2. phagocytosis
  3. Virus infects the cell itself
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55
Q

How does the dendritic cell MHC expression differ by location?

A

Dendritic cells in tissue = Low expression

Dendritic cells in lymphoid tissues = High

56
Q

What antigens can dendritic cells present? (3)

A
  1. Peptides
  2. Viral antigens
  3. Allergens
57
Q

Where in the body are dendritic cells found?

A

Entire body

58
Q

Where are macrophages found in the lymph node?

A

Throughout

59
Q

How does the macrophage uptake antigen?

A

Phagocytosis

60
Q

How does macrophage MHC expression vary?

A

If it comes in contact with bacteria and cytokines, expression increases

61
Q

What antigens does the macrophage present? 2

A
  1. Particulate antigens

2. Intracellular and extracellular pathogens

62
Q

Where are macrophages found? 3

A
  1. Lymph tissue
  2. Connective Tissue
  3. Body cavities
63
Q

Where are B cells found in lymph node?

A

Follicle

64
Q

How do B cells uptake antigen?

A

Antigen-specific receptor (Ig)

65
Q

How does B cells MHC expression vary?

A

Always expressing, but can be activated to express even more

66
Q

What antigens do B cells present? 3

A
  1. Soluble antigens
  2. Toxins
  3. Viruses
67
Q

Where are B cells found? 2

A
  1. Lymph tissue

2. peripheral blood

68
Q

Cytosolic pathogens degrade where?
Bind to what class of MHC?
Present to what cells?
Effect on presenting cell?

A

Cytosol

Class I

Effector CD8 T cells

Cell death

69
Q

Exogenous antigens degrade where?
Bind to what class of MHC?
Present to what cells?
Effect on presenting cell?

A

Cytosol

Class I

Naive CD8 T cells

Presenting cell activates CD8 cell

70
Q

Intravesicular pathogens degrade where?
Bind to what class of MHC?
Present to what cells?
Effect on presenting cell?

A

Endocytic vesicles

MHC Class II

Effector CD4 T cells

Activate to kill intravesicular bacteria and parasites

71
Q

Extracellular pathogens degrade where?
Bind to what class of MHC?
Present to what cells?
Effect on presenting cell?

A

Endocytic vesicles

Class II

Effector CD4 T cells

Activation of B cells to secrete Ig to eliminate pathogen

72
Q

What provides so much diversity to MHC genes? (2)

A
  1. Polygeny = Different class genes

2. Polymorphic = Variants of each gene

73
Q

Which MHC class I isotypes present antigen to CD8 T cells? 3

A

HLA-A
HLA-B
HLA-C

74
Q

Which MHC isotypes interact with NK cells? 2

A

HLA-E

HLA-F

75
Q

Which MHC isotypes interact with CD4 T cells? (3)

A

HLA-DP
HLA-DQ
HLA-DR

76
Q

Which MHC isotypes are intracellular and aid in antigen presentation process? (2)

A

HLA-DM

HLA-DO

77
Q

Each person expresses how many copies of each HLA?

From whom?

A

2 Copies

1 copy from each parent

78
Q

Why is it important to have different HLA types and a diverse MHC?

A

Allows for a greater diversity of peptides to be presented

79
Q

What encodes 1 HLA-DR?

A

HLA-DRB1 and DRA gene

80
Q

How might someone make more than 1 DR from a single chromosome?

A

Contain an additional DRB cassette

81
Q

If no extra cassettes are present, how many DR genes will an individual express?
If one is present on one chromosome, how many DR?
If one is present on two chromosomes how many DR?

A

2

3

4

82
Q

How many MHC-II genes can an individual express per professional APC?

Why?

A

6-8

2 DP + 2 DQ + (2-4) DR

83
Q

What are the domains involved in MHC class 1?

A

Alpha 1, Alpha 2, Alpha 3

84
Q

What are the domain involved in MHC class 2?

A

Alpha 1, Alpha 2, Beta1, Beta 2

85
Q

Anchor residues (2-3 AA’s) on the MHC allow for what?

A

Binding of peptide to the MHC within peptide binding groove

86
Q

Non-anchor residues on MHC allow for what?

A

Recognition by T cells

87
Q

MHC I present peptides of what size?

A

8-11 AA’s long

88
Q

MHC II present peptides of what size?

A

10-30 AA’s long

89
Q

Promiscuity in anchor residues allow for what?

A

Small number of MHC molecules to handle a variety of pathogens

90
Q

The T cell receptor recognizes what? (2)

A
  1. MHC (self)

2. Peptide (non-self)

91
Q

Does the T cell have to recognize the MHC and peptide simultaneously?

A

Yes

92
Q

MHC-II presents antigens from where?

A

Extracellular sources

93
Q

MHC-I presents antigens from where?

A

Intracellular sources

94
Q

Endogenous antigens are usually presented by what? (2)

A
  1. Cancer cells

2. Virus-infected cells

95
Q

4 main steps in antigen presentation to MHC?

A
  1. Antigen uptake
  2. Antigen processing
  3. MHC biosynthesis
  4. Peptide-MHC association
96
Q

Peptides for MHC-I presentation are broken down where?

What type of enzymes perform this?

A

Proteasome in the cytosol

Trypsin/Chymotrypsin-like activity

97
Q

Degraded proteins from MHC-I proteasome are transported where? How?

A

ER using Transporter associated with Antigen Processing (TAP)

98
Q

What prevents MHC-I molecules from interacting with antigen in the ER?
Examples? (5)

A

Chaperone protein interaction

Calnexin, Tapasin, Calreticulin, ERp57, and PDI

99
Q

What are the steps in MHC folding and peptide loading? 5

A
  1. Class I heavy chain is stabilized by calnexin
  2. Calnexin released
  3. Beta2-microglobulin binds and forms peptide loading complex with calreticulin, tapasin, TAP, ERp57, and PDI
  4. Peptide delivered by TAP binds to class I heavy chain forming mature MHC-I molecule
  5. MHC-I dissociates from peptide-loading complex and is exported from the ER
100
Q

So what must happen before MHC-I moves to cell surface?

A

Load a peptide

101
Q

Are self peptides ever loaded onto MHC-I?

A

Yes, but T cells know not to attack these cells

102
Q

What are the steps of peptide trimming in the ER? 3

A
  1. MHC-I loaded with a peptide that is too long at N terminus
  2. ERAP removes N-terminal AA’s to give correct size of 8-10
  3. MHC-I travels to cell surface
103
Q

How does the MHC-II presentation begin with uptake from ECF? (4)

A
  1. Antigen taken up from ECF into vesicle
  2. Endosomes are inactive due to neutral pH
  3. Vesicles acidify allowing proteases to work
  4. Vesicle with peptides fuses with vesicle containing MHC II
104
Q

What are the steps of peptide loading in MHC-II? 6

A
  1. Invariant chain blocks binding of peptides to MHC-II in ER
  2. Vesicle pinches off
  3. Upon contact with acidified endosome, Invariant chain cleaved off but leaves CLIP fragment
  4. CLIP blocks binding of peptides to MHC-II in vesicles
  5. HLA-DM facilitates release of CLIP, allowing peptides to bind
  6. MHC-II moves to
105
Q

Overall, what are the five basic steps of MHC-II presentation?

A
  1. Uptake of ECF proteins into vesicles
  2. Processing of vesicles in endosomal vesicles
  3. Synthesis and transport of MHC-II to endosomes
  4. Peptide endosome and MHC-II vesicle fuse and loading occurs
  5. Expression of peptide-MHC-II
106
Q

CD8 T cells bind to what on the MHC class I?

A

Alpha3 domain

107
Q

CD8 T cells upon binding to MHC class I do what?

A

Release cell destruction signals

108
Q

CD4 binds to what on the MHC class II?

A

Beta2 domain

109
Q 
CD4 does what upon binding to an MHC class II?
Which will do what? 1
A

Cytokine production

  1. Activate macrophages
  2. Activate B cells to make antibodies
110
Q

What have pathogens done to combat MHC presentation?

A

Found ways to evade host responses

111
Q

Total removal of the MHC does what?

A

Makes the cell more recognizable by NK cells

112
Q

MHC class I displays what proteins? (4)

A
  1. Self antigens
  2. Viral
  3. Bacterial
  4. Tumor
113
Q

Function of calnexin?

A

Retain partially folded state of MHC class I

114
Q

MHC class I loading complex contains what? (3)

A

Calreticulin
Erp57
Tapasin

115
Q

Function of calreticulin?

A

Chaperone

116
Q

Function of Erp57? 3

A

Chaperone, enzyme, maintain bonds

117
Q

Function of Tapasin?

A

TAP-associated protein that bridges MHC class I and TAP

118
Q

What is the stability of MHC molecules when not bound to antigen or chaperones?

A

Very unstable

119
Q

What is responsible for breaking down intracellular proteins and transporting them? 2

A
  1. Proteasome: Degrades

2. TAP proteins: Transport to ER

120
Q 
Upon leaving the ER in a vesicle, where does the MHC class II protein go? 
What happens during this process?
A

Through the Golgi to the surface

Invariant chain degraded leaving only CLIP

121
Q

Why must the MHC complex be stable at cell surface? 2

A

Dissociation would cause:

  1. Pathogens to escape detection
  2. Other cells to pick up antigens and be killed
122
Q

How tight is the MHC-Peptide complex?

A

Very, requires denaturation to dissociate

123
Q

Without bound peptide, MHC-I at cell surface does what? 3

A
  1. Conformation change
  2. Beta2-microglobulin dissociates
  3. alpha chain internalized and degraded
124
Q

Without bound peptide, MHC-II at cell surface does what? 3

A
  1. MHC-II’s aggregate
  2. Internalized
  3. Degraded
125
Q

What is the relative specificity of MHC’s?

A

Very broad, many different peptides can bind to the same MHC molecule

126
Q

Each T cell responds to what?

A

Single peptide bound to an MHC molecule

127
Q

What is required for an MHC to be stable at cell surface?

A

Bound peptide

128
Q

3 components of stable peptide-MHC2 complex?

A

Polymorphic alpha chain
Polymorphic Beta chain
Peptide

129
Q

3 components of stable peptide-MHC1 complex?

A

Polymorphic alpha chain of MHC
Beta2-microglobulin
Peptide

130
Q

What enzymes are responsible for MHC-II peptide generation?

A

Endosomal and lysosomal proteases

131
Q

What enzymes are responsible for MHC-I peptide generation?

A

Cytoplasmic proteasome

132
Q

Where is site of peptide loading of MHC for class II?

A

Specialized vesicles

133
Q

Where is site of peptide loading of MHC for class I?

A

ER

134
Q

Molecules involved in transport of peptides and loading of MHC-II molecules? 2

A

Invariant chain

HLA-DM

135
Q

Molecules involved in transport of peptides and loading of MHC-I molecules?

A

TAP

MICRO (22 decks)

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