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Block 5 > Immunology - Week 1 > Flashcards

Immunology - Week 1 Flashcards

1
Q

What is an Immunogen?

A

an antigen that induces an immune response

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2
Q

What is an Antigen?

A

A molecule that binds to (is recognized) by antibody or T cells

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3
Q

What factors will DECREASE immunogeicty?

Regarding:
Size
Dose
Route
Composition
Form (2)
Similarity to self protein
Adjuvants (2)
Interaction with host MHC
A 
Size: Small (MW <2500)
Dose: High or Low
Route: intravenous or intergastric
Composition: Simple
Form: Soluble and Native
Similarity to self protein: Few differences
Adjuvants (2): Rapid Release and No Bacteria
Interaction with host MHC: Ineffective
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4
Q

What factors will INCREASE immunogeicty?

Regarding:
Size
Dose
Route
Composition
Form (2)
Similarity to self protein
Adjuvants (2)
Interaction with host MHC
A 
Size: Large
Dose: Intermediate
Route: Subcutaneous 
Composition: Complex
Form: Particulate and Denatured
Similarity to self protein: Multiple differences
Adjuvants (2): Slow release and Bacteria
Interaction with host MHC: Effective
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5
Q

What mutation results in Chrones Disease?

A

A mutation in Nod-like receptors that cause over-activation of immune system

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6
Q

Which cells come from the common myeloid progenitor? (6)

A

Erythrocytes, Platelets, Basophils, Eosinophils, Neutrophils, Monocytes

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7
Q

Which cells come from the Common Lymphoid Progentior? (3)

A

B lymphocytes, T lymphocytes, NK Cells

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8
Q

What are the physical characteristics of a monocyte? (2)

A

Large cell

Lots of cytoplasm

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9
Q

What are the physical characteristics of a lymphocyte?

A

Little cytoplasm

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10
Q

What are the physical characteristics of a neutrophil?

A

Awkwardly shaped, multi-lobed nucleus and small granules

Most abundant immune cell in circulation

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11
Q

What are the physical characteristics of a Eosinophil?

A

Purple nucleus with a ton of red granuals

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12
Q

What are the defining physical characteristics of Basophils?

A

Purple dots

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13
Q

What are the defining physical characteristics of Mast Cells?

A

Purple dots

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14
Q

What do Basophils release?

A

IL4

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15
Q

What do Mast Cells release? (2)

A

Heparin and Histamine

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16
Q

What is the primary role of Dendritic Cells?

A

Dendritic cells are Antigen Presenting Cells - primary role is to transport and present microbial antigens to T lymphocytes in peripheral lymphoid tissues

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17
Q

What do Natural Killer Cells secret? (2)

A

The cytotoxins perforin and granzyme

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18
Q

What activates Natural Killer Cells? (4)

A

IFN-a, IFN-b, IFN-y, IL-12

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19
Q

What are the Primary (generative) Lymphoidal Tissues? (2)

A

Bone Marrow and Thymus

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20
Q

What are the Secondary (Peripheral) Lymphoid Tissues? (3)

A

Lymph Nodes, Spleen, and Mucosal or Skin-associated lymphatic tissue (MALT/SALT)

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21
Q

What is the role of Bone Marrow? (2)

A

Generation of hematopoietic progenitors

B lymphocyte maturation

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22
Q

What is the role of the thymus?

A

T Cell maturation

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23
Q

What is the structure of the thymus? (2)

A

There is a Cortex on the outer edges and the Medulla in the middle

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24
Q

What is contained in the periarteriolar lymphoid sheath (PALS) and where is this?

A

T Cells in the Spleen

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25
Q

What is contained in the follicle and where is this?

A

B Cells in the Spleen

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26
Q

How can you differentiate between the T Cell zone and the B cell zone in an H&E stain?

A

The B cell zone (follicles) will be light blue, while the T Cell Zone (PALS) will be dark blue.

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27
Q

What color do T Cell Zones and B Cell Zones stain respectively?

A

T Cell Zone: red

B Cell Zone: green

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28
Q

What is a Peyer’s patch?

A

Specialized lymphatic tissue in the Ilium

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29
Q

What do all innate immune defenses have in common? (3)

A

1) They rely on mechanisms that exist before infection
2) They are capable of responding rapidly to microbes
3) They react in the same way to repeat infections

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30
Q

What is the role of epilthelia in the immune system? (2)

A

1) Physical barrier to infection

2) Killing of microbes by locally produced antibiotics (AMPS)

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31
Q

What is an AMP and what is its mechanism? (antimicrobial peptide)

A

AMPs are peptides created by epithelial cells that are targeted towards microbe-containing environments (ex. GI lumen), they act alone to kill bacteria, fungi and virus by forming pores in their membranes.

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32
Q

What is the AMP that is specific to humans called?

A

defensins

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33
Q

What is Tamm-Horsfall protein (THP)

A

A part of epithilia defense. Inhibits uropathogenic E. coli from binding to epithelia along the urinary tract

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34
Q

What is Lactoferrin?

A

A part of epithilia defense. A glycoprotein that sequesters free iron, which is essential for bacteria. Also oxidizes and breaks bacteria cell walls.

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35
Q

What is the role of Mucus in the immune system?

A

A part of epithelial defense. A glycocalyx that prevents microbes from reaching the epithelial surface.

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36
Q

What is the purpose of commensals? (4)

A

1) compete for resources with more virulent organisms
2) produce their own AMPs
3) keep innate immune cells in an “attentive” state
4) lower vaginal pH

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37
Q

What are examples of resident macrophages?

A

1) Microglial cells (CNS)
2) Kupffer cells (liver)
3) Alveolar macrophages (lung)
4) Osteoclasts (bone)

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38
Q

What is the difference between an activated and unactivated DC cell?

A

unactivated: serve as sentinel cells in nearly every tissue
activated: moves to draining lymph nodes, where they stimulate adaptive immunity

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39
Q

What is Chronic Granulomatous Disease?

A

Deficiency in PMN function, associated with chronic and severe bacterial/fungal infections

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40
Q

Upon ingestion, what methods to phagocytes use to kill microbes? (4)

A

1) Phago-Lysosome fusion: lysosome fuses with phagosome and releases enzymes
2) Myeloperoxidase (MPO): produces HOCL from H2O2 and Cl-
3) NADPH oxidase: produces superoxide
4) iNOS: produces nitric oxide from arginine

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41
Q

What enzymes do lysosomes contain to kill microbes? (5)

A

Lysozyme, Defensins, Lactoferrin, Hydrolases, MPO

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42
Q

What is puss made up of? (3)

A

1) The accumulation of live and dead PMNs
2) Material destroyed by the PMNs
3) enzymes

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43
Q

What are the characteristics of an activated macrophage? (3)

A

1) enhanced phagocytosis due to increased transcription and translation of phagocytosis associated enzymes
2) secrete pro-inflmmatory cytokines
3) couple phagocytosis to antigen presentation on MHC class II molecules

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44
Q

How do DC cells differ from macrophages? (3)

A

DC cells:

1) are more efficient at processing phagocytosed microbes into antigens
2) “dentrites” extend from cell body
3) better at moving to lymph

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45
Q

What is the purpose of Granulocytes in the immune system?

A

defense against helminth parasites

46
Q

What are the granulocyte cells? (3)

A

Eosinophils, Basophils, Mast cells

47
Q

How do granulocytes kill parasites?

A

A receptor binds to the helminth parasite and the granulocyte releases its granules into the EC space (termed “degranulation”)

48
Q

What activates phagocytes?

A

PAMPS and DAMPS

49
Q

What activates granulocytes?

A

Ag-bound IgE binding cell surface FcRI

50
Q

What are the contents of granules? (5)

A

1) vaso-active amines (histamine): cause smooth muscle contraction/parasite expulsion from gut
2) Proteases: disrupts parasite tegument
3) Prostaglandins
4) Leukotriens
5) Cytokines

51
Q

Why are NK cells considered part of the innate immune system? (2)

A

1) Dependent on activating receptors that are germline-encoded (as oppose to through recombination)
2) Response not dependent on previous antigen exposure

52
Q

What are the functions of NK cells? (3)

A

1) Kill virus infected cells by lysis
2) Kill tumors by lysis
3) Kill phagocytosed microbes

53
Q

How do NK cells kill phagocytosed microbes? (3)

A

1) Macrophages that have engulfed a microbe release interluekin-12 (IL-12).
2) NK Cells respond to IL-12 by releasing interferon gamma (IFN-y)
3) IFN-y activates macrophages to kill phagocytosed microbes

54
Q

What is the relative abundence of NK cells?

A

Low abundance, less than 10% of lymphocytes

55
Q

What markers do NK Cells express? (3)

A

CD16, CD56, CD2

56
Q

What markers do Nuetrophils express?

A

CD16

57
Q

What markers do Monocytes and macrophages express?

A

CD16

58
Q

What markers do T helper and Cytotoxic cells express?

A

CD56

59
Q

How are NK cells activated to kill a cell?

A

NK cells have an inhibitory receptor and an activating receptor. The inhibitory receptor will bind to a self class I MHC molecule. The activating receptor will bind to an activating ligand.

NK cells will be activated when the inhibitory receptor is not engaged by MHC class I molecules AND when the activating receptor is engaged by activating ligands.

60
Q

How are NK cells inactivated?

A

NK cells have an inhibitory receptor and an activating receptor. The inhibitory receptor will bind to a self class I MHC molecule. The activating receptor will bind to an activating ligand.

NK cells will be inactivated when the inhibitory receptor is engaged regardless of whether the activating receptor is engaged or not.

61
Q

How do NK cells compliment the role of T cells?

A

Many viruses will down-regulate MHC in order to evade the adaptive immune system. While successful, down regulating MHC will then allow NK cells. and thus the innate immune system, to kill the infected cell because it’s inhibitory receptor will not be bound.

62
Q

How is NK cell lysis of infected or tumor cells carried about? (5 steps) Include the roles of three important molecules involved in the granule.

A

1) NK cell forms tight junctions with target cell
2) releases Granzyme and Perforin in a complex with Serglycine
3) Granule enters the cell via endocytosis
4) Granzme is released via perforin dependent process
5) Granzyme induces apoptosis

63
Q

What is anti-body dependent cellular cytotoxicity (ADCC?)

A

Anti-bodies of certain IgG subclasses bind to infected cells. The NK cell’s Fcy receptor recognizes these antibodies and is activated, killing the infected cell.

64
Q

What is the source of peptides that load onto Class I MHC molecules?

A

Inside (Cytoplasm)

65
Q

What is the source of peptides that load onto Class II MHC molecules?

A

Outside (Extra-Cellular)

66
Q

How are proteins tagged for degradation?

A

Ubiquitin chain added to lysine residues

67
Q

What are the similarities between peptides that bind to Class I MHC molecules? (3)

A

1) 9 residues long
2) hydrophobic amino acid at the 9 position
3) An anchoring region at positions 2 and/or 3 (Glycine and Proline at the 2 and 3 position in one example, tyrosine at the 2 position in another example)

68
Q

How does a virus infected cell create more peptides suitable for binding to Class I MHC molecules? (3 steps)

A

1) IFN-y induces expression of 3 replacement proteosome subunits called LMP
2) these subunits up-regulate chymotrypsin
3) chymotrypsin is a protease that cleaves peptides before hydrophobic amino acids

69
Q

What is an immunoproteosome?

A

A proteosome that has incorporated the 3 beta-protesome subunits (LPMs)

70
Q

What has to happen to a protein in order to get into a proteosome? (2)

A

1) ubiqutin cap needs to be removed

2) protein needs to be unfolded/stretched out

71
Q

What does the proteosome’s 19s cap do?

A

Removes the ubiqutin cap so the protein can enter proteosome

72
Q

What does the TAP molecule do?

A

Transports peptides into the ER

73
Q

How long are peptides after being degraded by the proteosome?

A

4-20 amino acid residues

74
Q

What is the structure of the TAP transporter?

Membrane spanning domains?
Substrate?
Types of peptides?
Size of peptides?

A

Membrane spanning domains: 12
Substrate: only peptides
Types of peptides: Peptides ending in hydrophogic aa (Leucine, Isoleucine, valine or methionine)
Size of peptides: 6-15 aa

75
Q

What is the structure of Class I MHC molecule?

Subunits?
Substrate Size Range?

A

Subunits: light chain (beta-2 microglobulin) and a heavy chain
Substrate Size Range: 8-10 aa

Note* the peptide itself can be considered a subunit because it is needed to keep the molecule together

76
Q

What is tapasin?

A

Tapasin tethers newly synthesized class I MHC molecules to TAP so it is in close proximity for peptides to bind

77
Q

How does a T cell know whether it is seeing self or foreign peptide? (4 steps)

A

1) in the newborn, T cells have the capacity to recognize everything
2) T cells that tightly bind to self-peptide + self-MHC molecule die
3) T cells that don’t bind to anything die
4) the only T cells that are left DON’T bind tightly to self-peptide + self-MHC molecules

78
Q

When does a T cell kill a cell?

A

T cells kill cells when they tightly bind to the peptide + MHC molecule

79
Q

What is alloreactivity?

A

When a T cell binds tightly to someone elses peptide + MHC complex, thus killing that cell (graft rejection)

80
Q

What is the light chain of a Class I MHC molecule called?

A

beta-2 microglobulin

81
Q

What is the structure of a Class II MHC molecule?

Subunits?
Substrate Size Range?

A

Subunits: alpha heavy chain, beta heavy chain
Substrate size range: 10-16 (can be 30 or longer)

Note* the peptide itself can be considered a subunit because it is needed to keep the molecule together

82
Q

What makes up the peptide-binding cleft for a Class I MHC molecule? Which domains? (2)

A

Heavy Chain - alpha1 and alpha2 domains

83
Q

What makes up the peptide-binding cleft for a Class II MHC molecule? Which domains? (2)

A

Alpha heavy chain and beta heavy chain - alpha1 and beta1 domains

84
Q

What mediates the proteolysis of antigen into peptides for Class II MHC molecules?

A

lysosomes

85
Q

What types of cells do Class I MHC molecules display their peptides to?

A

CD8 T cells

86
Q

What types of cells do Class II MHC molecules display their peptides to?

A

CD4 T cells

87
Q

What are cathepsins?

A

lysosomal protease

88
Q

What is the optimal p.H. for cathepsins?

A

p.H. of 5

89
Q

What is the MIIC?

A

the lysosome that makes up the MHC Class II compartment

90
Q

What is the role of invarient chain in the ER? (3)

A

1) Scaffold and stablizer for Class II MHC molecule
2) provides a barrier to peptides while the MHC molecule is in the ER
3) Molecular zip code for MHC to go to MIIC lysosome

91
Q

What is the role of invarient chain in MIIC?

A

1) Invarient chain is cleaved by lysosomal enzymes so that it only fills the peptide binding site (last piece called CLIP)
2) HLA-DM de-stabilizes peptides bound in the cleft
3) Peptides continue to bind until DM can not dislodge it

92
Q

What is the structure of the invarient chain bound to the Class II MHC molecules?

A

3 Invarient chains bind to 3 class II molecules to form a trimer

93
Q

What is CLIP?

A

The piece of inviarient chain left bound to the peptide binding site in the lysosome

94
Q

What is HLA-DM?

A

An enzyme that de-stablizes peptides bound in the peptide binding cleft of MHC Class II.

95
Q

How can self peptides be presented by class II MHC molecules?

A

Macrophages can engulf dead cells and brought to the lysosome

96
Q

What is cross-presentation and which cells do it?

A

Cross-presentation is the process that allows dendritic cells to present peptides on class I MHC molecules along with Class II MHC molecules despite engulfing the virus or bacteria without being infected.

97
Q

What is CD1?

What does it bind?
Similarity to Class I MHC?
Similarity to Class II MHC?
Which cell types have CD1?
Which cell types recognize complex?
A

Bind: CD1 is an antigen presentation molecule that binds lipids.
Like Class I MHC: lipid binds to b2m in cleft
LIke Class II MHC: travels with invarient chain to lysosome
Which cell is it in: Only present in antigen presenting cells
What cell type recognizes CD1: NK T cells recognize lipids with CD1

98
Q

Which cells are antigen presenting cells? (3)

A

B Cells, Dendritic cells, Macrophages

99
Q

Which cells contain MHC Class II

A

Only antigen presenting cells

100
Q

Why does cross-presentation need to happen?

A

Both CD4 and CD8 T cells are needed to eradicate an infection, so both microbial peptides need to be presented by both MHC Class I and MHC Class II molecules.

101
Q

If a dendridic cell engulfs a bacteria, which class MHC cell will present bacteria peptides?

A

Both Class I and Class II (because of cross-presentation

102
Q

What is passive immunity? How long does it last?

A

Transferring anti-bodies specific to a certain antigen to another host in order to impart immunity. Half life of a anti-body is only about 30 days so needs to give them the anti-body very couple months.

103
Q

What is MHC restriction?

A

T cell receptors bind to MHC molecules based on both the antigen and self-MHC molecule, so even if a T cell receptor is specific for an antigen, it won’t work unless it see’s the self MHC molecule as well.

104
Q

What genes are encoded by the Major Histocompatibility Complex Locus? (12)

A

Complex I: 3 genes: HLA-A, HLA-B, HLA-C (3 domains of the heavy chain)
Complex II: 6 genes: HLA-DR, HLA-DQ, HLA-DP (alpha and beta for each)
Related Proteins: HLA-DM, TAP, LMP

105
Q

What chromosome is MHC gene on?

A

6

106
Q

Genetically, how can T cells see such a wide verity of antigens? (3)

A

polygenic: 3 genes code for MHC I, 6 genes code for MHC II

Co-dominent: alleles from each parent will contribute to phenotype, so you will have 6 different alleles for Class I MHC contributing to structure.

Polymorphic: most polymorphic genes in body. Huge number of allel’s in the population, providing a large variety of possible phenotypes

107
Q

What are the chances that 2 siblings share the same ten MHC gene products? Why is it so high?

A

25% - because the genes are inherited as a chunk (they are linked) unless there is recombination between the genes theselves (rare)

108
Q

Which domains of MHC Class I and Class II molecules show the greatest polymorphism? Why?

A

Class I: alpha1 and alpha2
Class II: beta1

These domains are membrane distal, these domains have a direct effect on which peptides bind.

109
Q

How do MHC molecules each individual has bind to such a verity of antigens?

A

1) the loose constraints that limit what type of peptide can bind allows for up to 1000 different types
2) each allelic version binds a different set of peptides

110
Q

What are the benefits of MHC polymorphism?

A

A virus may escape notice by one individual’s MHC molecules, but not an entire populations.

111
Q

What consistent characteristic do non-responders to the Hepatitis B vaccine share? Why does this cause non-responsiveness?

A

They have the alleles HLA-DR7 and HLA-DR3

Causes vaccine not to work because T-Cells are defective in recognizing the antigen

112
Q

What is Ankylosing Spondylitis and how is it linked to the immune system? What is a possible reason?

A

It’s an inflammatory disease of vertebral joints.

93% of those who have it also have HLA-B27

Hypothesis: B27 might be good at presenting a similar peptide to a bacteria peptide, so when T-Cells respond to the bacteria peptide, they also respond to their own cells.

Block 5 (23 decks)

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