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IHO Week 5 > Regulation of the Immune System > Flashcards

Regulation of the Immune System Flashcards

1
Q

What interaction is responsible for the upregulation of IL-2?

A

T-cell CD28 and APC B7 (CD80/86)

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2
Q

What interaction is responsible for the downregulation of IL-2?

A

T-cell CTLA4 and APC B7 (CD80/86)

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3
Q

Intracellular organisms elicit what type of a response?

A

Cell-Mediated Response from NK Cells and CD8+ T-Cells

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4
Q

Extracellular organisms elicit what type of a response?

A

Humoral Response from Complement and Antibody-Mediated interactions

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5
Q

What is CCR7 important for?

A

Trafficking the Dendritic Cell to the Lymph Nodes

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6
Q

What are the symptoms of IPEX?

A

Rashes on the skin and hair falling out, collitis, diarrhea

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7
Q

What is the cause of IPEX?

A

An X-Linked inborn lack of Treg cells that cause a severe autoimmune inflammation through immunodysregulation, polyendocrinopathy, and enteropathy.

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8
Q

What is the function of IL-35?

A

Autoregulatory positive-feedback loop to produce more Treg cells

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9
Q

What are the 3 ways that can lead to autoimmunity?

A

1) Absence of Tregs
2) Insufficient Treg effector functions
3) Resistance of effector T-Cells to Treg effector functions

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10
Q

What happens at the end of the immune response to T-Cells?

A

Apoptosis of Antigen-Specific T-Cells

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11
Q

What does anergy occur in mature dendritic cells?

A

Lack of co-stimulatory signals in the presence of strong MHC expression

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12
Q

What co-stimulatory molecules are necessary for tolerogeneic DC:T-Cell interactions?

A

Surface Molecules: E-Cadherin, PD-1, CD103, CD152 (CTLA-4), ICOS-L (CD275)

Cytokines: IL-10, TGF-B

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13
Q

What is the function of Regulatory T-cells (Treg)?

A

Preventing and suppressing immune responses (prevents autoimmune diseases)

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14
Q

What percentage of T-cells do Tregs make up?

A

10%

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15
Q

What surface molecules are present in immunogenic Dendritic Cells?

A

High CD86
High MCHII
High CD40
High CCR7

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16
Q

What surface molecules are present in tolerogenic Dendritic Cells express?

A

Low CD86
Low MHCII
Low CD40
Low CCR7

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17
Q

What are the pro-inflammatory cytokines that immunogenic Dendritic Cells secrete with presented with antigen?

A

IL-12

TNF-alpha

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18
Q

What is the function of immunogenic Dendritic Cells?

A

T-cell proliferation and activation of effector functions

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19
Q

What is the function of tolerogenic Dendritic Cells?

A

Clonal deletion or anergy of antigen-specific T-cells

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20
Q

What are the 4 mechanisms of Treg effectors?

A

1) Immunosuppressive cytokines (IL-10, TGF-B, IL-35) –> Cell Cycle Arrest
2) IL-2 Consumption –> Bim-Mediated Apoptosis
3) Cytolysis (Granzyme-Mediated) –> Apoptosis
4) Modulation of DC Maturation and Function (CD152/CTLA4 CD80/86) –> Cell Cycle Arrest

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21
Q

How does IL-35 work with Treg?

A

IL-35 is an autoregulator for a positive feedback loop to produce more Treg Cells.

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22
Q

What are the 3 ways that loss of Treg Effector Functions can cause autoimmunity?

A

1) Absence of Tregs (IPEX)
2) Insufficient Treg Effector Functions (RA)
3) Resistance of Effector Tcells to Treg Effector Functions (TNF)

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23
Q

What is Grave’s Disease?

A

Over-production of thyroid hormones caused by autoantibodies from B-cells and plasma cells that act as agonists for the thyroid stimulating hormone receptor

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24
Q

What are the 3 mechanisms of B-Cell Tolerance?

A

1) Clonal Deletion
2) Receptor Editing
3) B-Cell Intrinsic Mechanisms

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25
Q

Define Clonal Deletion in B-Cell Tolerance.

A

Induction of apoptosis via inhibition of survival signals or activation of death receptors

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26
Q

Define Receptor Editing in B-Cell Tolerance.

A

Continued V(D)J recombination to avoid self-reactivity

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27
Q

Define the 2 B-Cell Intrinsic Mechanisms in B-Cell Tolerance.

A

Anergy, downregulation of the BCR, upregulation of CD5
OR
Lack of T-Cell help or survival factors

28
Q

What type of response is evoked with administration of antigens subcutaneously or intradermally?

A

Active Th1 CD4+ T-Cell Immune Response

29
Q

What type of response is evoked with administration of antigens orally, IV or aerosol?

A

Tolerance or a Th2 CD4+ T-Cell Immune Response

30
Q

How is IFN-Gamma production induced in T-Cells and NK Cells and what is the consequence of this?

A

IL-12 stimulates IFN-Gamma production, which leads to the differentiation of Th1 T-Cells

31
Q

How is IL-12 induced and what is the consequence of this?

A

Production of IFN-alpha early in viral infection to switch T-cells from Th2 to Th1.

32
Q

What Th1 cytokines promote what cell actions?

A 
IFN-y
TNF-B
IL-2
Macrophage Activation
Antibody-dependent cell-mediated cytotoxicity
Delayed Hypersensitivity
33
Q

What Th2 cytokines promote what humoral immune responses?

A 
IL-4, IL-5, IL-9, IL-10, IL-13
IgG1 and IgE isotype switching
Mucosal Immunity
IgA Synthesis
Mast Cell/Eosinophil Differentiation
34
Q

What Th17 cytokine promotes what cell action?

A

IL-17
Neutrophil Recruitment
and Inflammation

35
Q

How does IgG inhibit B-Cell differentiation?

A

By cross-linking the antigen receptor with the Fc receptor on the same cell

36
Q

What 2 ways can antibody-dependent B-Cell suppression occur?

A

Antibody blocking by soluble Ig binding to membrane Ig when there is too much antibody in the system
OR
Receptor cross-linking by membrane protein FcyRIIb binding soluble IgG in a plasma cell signaling apoptosis

37
Q

What are the 2 regulatory effect of immune complexes?

A

Inhibition through FcyRIIb
OR
Augmentation through complement CR2 binding to antigen and signaling the B-cell to undergo Class-Switching Recombination or Somatic Hypermutation

38
Q

What chemokine receptors do Th1 T-Cells express to attract what cells?

A

CXCR3 and CCR5

Monocytes

39
Q

What chemokine receptors do Th2 T-Cells express to attract what cells?

A

CCR3, CCR4, and CCR8

Mast Cells and Eosinophils

40
Q

What chemokine receptors do Th17 T-Cells express to attract what cells?

A

CCR6

Neutrophils

41
Q

Where are the two areas of the body that immune responses do not occur and what cytokines prevent an immune response?

A

Anterior chamber of the eye and the testes

TGF-B and IL-10

42
Q

What diseases are people with C1q, C1r, and C1s defects prone to?

A

Systemic Lupus Erythematosus (SLE)

Lupus Nephritis

43
Q

What susceptibility is increased with a deficiency in C3 (C2 or C4)?

A

Bacterial Infections

44
Q

What is TLR4 important for and what does polymorphism Asp299Gly result in?

A

TLR4 is an important sensor of gram negative bacterial infections, which results in higher increase in TNFa when stimulated with LPS.

45
Q

In Africans with the TLR4 polymorphism, what are they protected against?

A

Cerebral Malaria

46
Q

In Europeans with the TLR4 polymorphism, what are they susceptible to?

A

Septic Shock from the plague

47
Q

What mutation gives rise to a reduced number of T-Cells?

A

IL-7R alpha chain mutation

48
Q

What mutations gives rise to reduced numbers of T-Cells and NK-Cells, as well as impaired B-cell function?

A

Mutation in the common cytokine receptor y chain (yc)

–component in IL-2, IL-4, IL-7, IL_9, and IL-15 receptors

49
Q

What mutations increase susceptibility to mycobacterial infections?

A

IFNy receptor

IL-12 receptor

50
Q

What mutations in cytokine receptor genes are associated with SCID?

A

Defect in yc or Jak 3

Defect in IL-7R alpha

51
Q

What have mutations in the cytokine promotes been linked to?

A

Susceptibility to infections and autoimmune conditions

52
Q

What diseases has a mutation in the TNFalpha gene promoter region been associated with?

A

Cerebral Malaria
Lepromatous Leprosy
Mucocutaneous Leishmaniasis
Meningococcal Disease

53
Q

What mutation in cytokine promoters is associated with progression from HIV to AIDS?

A

Chemokine Receptor Gene-5 (CCR5)

54
Q

What genotype is resistant to HIV-1 infections?

A

Homozygous for the CCR5 mutation

55
Q

What is the root mutation causing IPEX?

A

FOXP3 mutation –> defective Treg Cells –> Failure of peripheral tolerance

56
Q

Define Central Tolerance.

A

Result of the removal of self-reactive lymphocytes in the central organs

57
Q

Define Peripheral Tolerance.

A

Inactivates T and B cells that escape central tolerance and exit to the periphery

58
Q

Due to the risk of disease flare-up in IPEX patients, what is contraindicated?

A

Vaccination

59
Q

How would you treat a flare-up of IPEX on exposure to pathogens?

A

IVIG

60
Q

What is APECED?

A

Autoimmune Polyglandular Syndrome Type 1

61
Q

How is APECED inherited?

A

Autosomal Recessive

62
Q

What is the root cause of APECED?

A

Defect in T-cell tolerance and production of autoantibodies to IL-17 and IL-22 (produced by Th17

63
Q

What abnormality might be found in the lymph nodes of individuals that lack the AIRE gene?

A

T-Cell zone expanded because negative selection is not present

64
Q

What would you expect to find if you transferred lymphocytes from AIRE deficient mice to RAG knock-out mice?

A

No recombination taking place, no B-Cells or T-Cells –> APECED

65
Q

What would you expect to find if you transferred lymphocytes from wildtype mice to RAG knock-out mice?

A

Normal transient phenotype that can fight a pathogen initially, but nothing major will happen.

66
Q

How might IVIG be an effective therapy for IPEX?

A

Blocking the immune system to never be stimulated so you get less risk for inflammation

IHO Week 5 (5 decks)

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