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1
Q

Primary function of IgM

A

Primary immune responses

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2
Q

Primary function of IgG

A

secondary immune responses

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3
Q

Primary function of IgE

A

allergic hypersensitivities

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4
Q

Primary function of IgA

A

External secretion, mucosal protection

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5
Q

Primary function of IgD

A

Unknown. Found on B cell surfaces

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6
Q

Which Ig is most associated with opsonization?

A

IgG

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7
Q

Which Ig is most associated with sensitization of mast cells?

A

IgE

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8
Q

Which Ig can activate complement?

A

IgM and IgG

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9
Q

What are the three methods by which antibodies mediate humoral immunity?

A

Neutralization
Opsonization
Complement activation

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10
Q

Gene segments in Ig light chain locus

A

V, J

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11
Q

Gene segments in Ig heavy chain locus

A

V, D, J

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12
Q

Order of rearrangements in Ig gene during B cell development

A

1) D-J rearrangement on heavy chain
2) V-DJ rearrangement on heavy chain
3) V-J rearrangement on light chain

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13
Q

Which stage of B cell development does heavy chain DJ rearrangement occur?

A

Pro B cell

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14
Q

Which stage of B cell development does heady chain V-DJ rearrangement occur?

A

Pre-B cells are formed once the heavy chain is rearranged and surrogate light chain combines to make the pre B cell receptor

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15
Q

Which stage of B cell development does the light chain rearrange?

A

pre-B cells turn into immature B cells when the light chain successfully rearranges to form IgM on the cell surface

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16
Q

Which enzyme is involved with Ig gene rearrangement?

A

RAG1 and RAG2

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17
Q

What enzyme adds random nucleotides between V, D and J segments during gene rearrangement?

A

TdT does “N nucleotide addition”

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18
Q

Which T cell receptor chain is analogous to the B cell receptor light chain?

A

The T cell alpha chain is analogous to the B cell light chain (V and J segments, no D)

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19
Q

Describe the timing of thymic development during embryogenesis

A

Wk 7-8: HSC colonize the thymus gland
Wk 12-13: Mature T cells are detectable in thymus
Wk 13-14: Mature T cells leave thymus and establish peripheral T cell pool

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20
Q

What is DiGeorge syndrome?

A

A deletion in c22 leads to recurrent infections due to loss of the thymus and T cells

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21
Q

What is the clinical significance of the FOXN1 gene?

A

FOXN1 is essential for the development of thymic epithelial cells. Without this gene, HSCs are not recruited to the thymus and T cells will not be made

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22
Q

What cytokines are produced by thymic epithelial cells?

A

IL7, SCF, IL1, IL6, IL15, TSLP

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23
Q

What is the major cell surface ligand of thymic epithelial cells?

A

Delta-like 1,4 is the ligand for the Notch receptor

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24
Q

What CD marker is activated between HSC and T/NK progenitor cells?

A

CD7

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25
What CD marker do Pre-T cells have that T/NK do not?
CD1a
26
What T cell pregenitor is the final precursor for alpha/beta and gamma/delta T cells?
immature single positive
27
What cytokine is required for recombination of TCR and BCR genes?
IL7
28
What surface markers are characteristic of NKT cells?
T cell markers (TCR alpha/beta) and NK markers (CD56)
29
What surface markers are characteristic of Tregs?
CD4+, CD25+ | Also have FOXP3 TF expressed
30
What are the 2 signals required for thymus dependent activation of B cells?
1) MHC-TCR | 2) CD40-CD40L
31
What are the B cell stimulatory cytokines?
IL 4, 5, 6
32
What enzyme is required for isotype switching?
AID
33
What are the 4 main outcomes of a Class II MHC interacting with a CD4 Th0 cell?
Possible responses: | Th1, Th2, Th17, Treg
34
What is the dominant cytokine and the main transcription factor associated with a Th1 response?
Cytokine: IL12 TF: T-Bet
35
What is the dominant cytokine and the main transcription factor associated with a Th2 response?
Cytokine: IL4 TF: GATA-3
36
What is the dominant cytokine and the main transcription factor associated with a Treg response?
Cytokine: TGF-beta TF: FoxP3
37
What is the dominant cytokine and the main transcription factor associated with a Th17 response?
Cytokine: IL23 TF: ROR
38
Describe the main steps in a TMMI response
1) Pathogen phagocytosed by DC or macrophage 2) IL 12 released from phagocytic cell 3) Pathogen fragments presented to Th0 on MHCII 4) Th0 converted to Th1 in presence of IL12 5) Th1 cell produces IL2, IL21 and IFNgamma, which activate Macrophages 6) Activated macrophages produce IL1, IL6, IL8 and TNFalpha
39
What are the 4 mechanisms that initiate/enhance CD8 cytotoxicity?
1) NK cells see abnormal MHC, produce IFNgamma 2) TLRs on DCs present to CD4 via MHCII, CD4 activates CD8 3) TLR sensitive to DNA/RNA can activate CD8 4) Cross presentation by DCs on MHC I and II
40
What determines whether IL21 will promote a Th1 or a Th2 response?
The presence of IFNgamma promotes Th1 | Without IFN, Th2 will be stimulated
41
What cytokines are the major drivers of B cell differentiation in Th2 responses?
IL 5, 6, 10
42
What cytokines associated with Th2 responses supress Th1 responses?
IL 4, 10 and 13 supress Th1 reactions
43
What is the trio of cytokines associated with Th17 responses?
IL23, IL6, and TGFbeta
44
What cytokines are strong inhibitors of Th17?
IL4 and IFNgamma
45
Describe the cytokine profile that stimulates a Treg response
TGFbeta and IL10 in the absence of IL6
46
Activation of the classical pathway of complement
Immune complexes Fc regions are recognized by C1qrs | C1q binds to the Ab, C1r activated and then activates C1s forming a C3 convertase
47
Activation of the lectin pathway of complement
MBL binds to mannose on microbial surfaces | MASP1 and MASP2 are proteases that form C3 convertase
48
What is the result of an activated classic or lectin pathways?
C1s/MASP-2 cleavs C4 to C4a and C4b C4b binds with C2 on cell surface C4b2a is C3 convertase, which cleaves C3 C3b is powerful opsonin, promotes phagocytosis
49
What molecules make up the C5 convertase?
C4b2a3b is the C5 convertase
50
Describe the effects of C5 convertase
C4b2a3b cleaves C5 into C5a and C5b C5b combines with C6 and C7 and binds the membrane C8 inserts into the membrane and then 16 C9 molecules form MAC "hole" in membrane
51
Describe the steps of the alternate pathway of complement activation
C3 is slowly hydrolyzed and then can bind Factor B Factor D cleaves Factor B to Bb and Ba C3b binds cell surface, Factor B can bind and then get cleaved by D to form C3bBb, stabilized by Factor P, a C3 convertase Another molecule of C3b associates to form C3bBbC3b, a C5 convertase MAC complex formed
52
What are the two types of opsonization?
Complement mediated: Cr1 receptors on phagocyte bind C3b on cell surface FcR mediated: FcRs on phagocyte bind Abs
53
What factors inhibit C1?
C1INH
54
What factors inhibit C3?
DAF, C4BP, CR1, MCP, factor I
55
What factors inhibit C5?
Factor I, Factor H and CR1
56
What factors inhibit MAC?
CD59
57
What is the main chemokine that helps DCs navigate to lymph nodes?
CCL21 produced by HEVs and stromal cells
58
Type I hypersensitivity disease
Allergic response, IgE mediated
59
Type II hypersensitivity disease
Antibody directed against tissue antigens
60
Type III hypersensitivity disease
Immune complex mediated disease
61
Type IV hypersensitivity disease
Delayed hypersensitivity (TMMI)
62
What is the major balance between in immune complex disease?
Formation versus disposal of immune complexes
63
Ways to treat immune complex diseases
Eliminate the antigen Inhibit antibody formation Suppress inflammation
64
How do FcR (gamma) regulate APCs and lymphoid cells differently?
In APCs, cross linkage of FcRs triggers phagocytosis and degradation In B cells, cross linkage of FcRs with BCRs downregulates the production of antibody by the B cell
65
How can FcRs be used to prevent fetal rejection due to Rh factors?
A Rh- mother in her second pregnancy is at risk to have an immune response against the Rh factor of her child. Administering IgG for Rh+ will cross link BCR and FcRs and downregulate the production of Rh+ antibodies
66
What is the difference between an isograft and an allograft?
isografts are between identical twins (perfect match) | allografts are between different peoples (not perfect match)
67
What is a complement dependent cytotoxicity assay tell us?
Whether or not a recipient has antibodies that will react with donor tissue
68
Describe direct allorecognition
Transplant recipient will have donor APCs migrating to their local lymph nodes and stimulating alloreactve recipient T-cells. In this situation, the entire APC is recognized as a foreign antigen
69
Which immune responses are triggered during specific rejection of a transplant?
Donor and host DCs stimulate Th2, B cells and Th1 (TMMI, CD8 and Th17) responses So basically, all of them
70
What causes hyperacute rejection?
Preexisting antibodies to donor blood group antigens
71
What are the strategies to prevent rejection?
Match MHC Block T cell responses to alloantigens Provide inhibitory signals (CTLA4), Tregs, or cytokines to override Th1, Th17 and CD8
72
What gene is deleted to allow for xenotransplation?
alpha-1,3 GT
73
What immune mechanisms are balanced by commensal microbiota?
Pro-inflammatory and anti-inlammatory | Th1/Th17 vs. Treg
74
How does B. Fragilis protect from/treat IBD?
B fragilis induces Tregs
75
Defend the hygiene hypothesis using Th1 and Th2 logic
Infections elicit Th1 responses, which inhibit Th2 responses from occuring. Without exposure to pathogens as a child, Th2 will not be as suppressed and the development of hyperreactive IgE is more possible
76
What is the mechanism of superantigens?
They bridge CD4 to MHCII, tricks into thinking normal Ag presentation is occuring
77
Toxic shock syndrome mechanism
Superantigen stimulates 20-30% of T cells, releases IFNgamma, which activates Macrophages to release tons of TNFalpha This causes decreased vascular resistance, shock, death
78
What is the diagnostic value of autoantibodies in the serum?
None. Most people have autoantibodies, so their presence doesn't help with diagnosis
79
Loss of AIRE function leads to:
multiple autoimmune neural/endocrine diseases due to failure of display in thymic medulla
80
The ratio between what two cytokines determines bone formation?
high OPG/RANKL protects bones from breakdown
81
What cytokines induce RANKL?
Proinflammatory cytokines IL 1,6,8, TNF, IL17
82
Which T cell response would you want to promote in order to prevent excess bone resorption?
Normal Th1, Th2 or balanced Th1/2 responses would inhibit IL17 and decrease chronic inflammation
83
What is the difference between M1 and M2 macrophages?
M1 are proinflammatory (IL1, 6, 8, TNF) | M2 are ant-inflammatory (TGFb, IL10)
84
What are the main opposing adipocytokines?
Leptin (proinflammatory) and Adiponectin (anti-inflammatory)
85
What is clinically important about visfatin?
Visfatin is a proinflammatory adipocytokine that is also pro-angiogenic. Blocking this could prevent fat expansion
86
What chemokine is associated with M1 machrophages in atherosclerotic plaques?
CCL2 attracts monocytes and then prohibits them from leaving the plaque
87
What chemokine is associated with immunosupressive environments around tumor cells?
CCL21
88
What is the relevance of the relevance of the PD1 receptor?
Tumors use this receptor on T cells to inhibit/kill them Tumor PD-L1 or 2 This interaction neutralizes any attacking cytotoxic T cells
89
What are the three targets for monoclonal antibodies that are promising treatments for cancer?
Block CTLA4 on the T-cells Block PD1 on T cells Block PD1L on cancer cells
90
What is a RAST assay?
Patient serum is added to a solid media with allergen bound. If IgE is sensitive to the antigen, then it will bind. Radio labeled anti-IgE is used to quantify amount
91
Treatment and prevention of allergies
Suppress the symptoms with drugs Immunotherapy: subcutaneous or sublingual Block/suppress with a monoclonal Anti-IgE Vaccinate?

Host Defense (3 decks)

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