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Sp 15-Micro Final > Immunological Tolerance and Autoimmune Disease > Flashcards

Immunological Tolerance and Autoimmune Disease Flashcards

1
Q

What is immunological tolerance?

A

A state of unresponsiveness for a particular antigen

LEARNED prior to exposure to the antigen

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2
Q

What is self tolerance?

A

Physiological state in which the immune system does NOT react destructively against self tissue.

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3
Q

Self tolerance may be induced in immature self-reactive lymphocytes within ________ or in mature lymphocytes in ________.

A

Generative lymphoid organs (bone marrow/thymus)

Peripheral Sites

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4
Q

What is central tolerance?

A

Tolerance that involves immature self-reactive lymphocytes within generative lymphoid organs

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5
Q

______ is functional unresponsiveness or “programmed ignorance.”

A

Anergy

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6
Q

Peripheral tolerance occurs in peripheral sites and occurs when ______ lymphocytes encounter self antigen.

A

Mature Self-reactive

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7
Q

True or False: Immunological tolerance is the failure to recognize antigen.

A

FALSE, it is an active response to a particular epitope and is just as specific as an immune response.

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8
Q

Tolerance may be _______ (self or oral) or may be _____ (prevent allergies, graft rejection, etc).

A

Natural

Induced

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9
Q

Reactivity is prevented by processes that occur ______ rather than being genetically pre-programmed.

A

during development

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10
Q

Which aspect of tolerance is considered to be the most important because it prevents the body from mounting an immune attack against its own tissues?

A

Self Tolerance

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11
Q

Which aspect of tolerance is considered to be the most important because it prevents the body from mounting an immune attack against its own tissues?

A

Self Tolerance

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12
Q

Central tolerance is programmed in T cells within the ____ and in B cells within the ______.

A

Thymus

Bone Marrow

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13
Q

What happens when lymphocytes do not bind MHC through their TCR?

A

They are destined to die by apoptosis

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14
Q

_______ selection occurs in the cortical region of the thymus.

A

Positive

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15
Q

What is “positive selection” within the thymus?

A

If the TCR of a lymphocyte recognizes MHC and binds antigen with LOW AVIDITY, the lymphocyte is sent to peripheral (secondary lymphoid organs) where it is able to mature and proliferate.

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16
Q

______ selection occurs in the medullary region of the thymus.

A

Negative

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17
Q

What is “negative selection” within the thymus?

A

If the TCR of a lymphocyte binds MHC with HIGH AVIDITY, the lymphocyte is deleted.

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18
Q

During maturation in the thymus, immature T cells that recognize antigens with high avidity will die (most) or_________(few).

A

Differentiate into regulatory T cells that will act to keep other T cells in check

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19
Q

Where do regulatory T cells come from?

A

Maturing T cells in the thymus that bind with high avidity or most often deleted, but some are allowed to differentiate into regulatory cells to monitor T cell activity.

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20
Q

Lymphocyte activation and tolerance is determined by:

  1. _________ of the antigens
  2. _______ of the antigen-specific lymphocytes
  3. types of _____ received when encountering antigens
A
  1. Properties
  2. State of maturation
  3. stimuli (costimulatory molecules)
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21
Q

A B cell Receptor is a _________.

A

Membrane bound antibody

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22
Q

Central tolerance in B cells will occur in immature B cells within the _______, where autoreactive cells will be _______ or _______.

A

bone marrow
eliminated
inactivated until rearrangement results in a new receptor

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23
Q

B cells that are self reactive will go through ________ which is a one-chance process.

A

Receptor Editing

  • if the receptor is still self-reactive = apoptosis
  • if the receptor is no longer reactive = maturation
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24
Q

Nature and concentration of self Ag determine the fate of B cells. For example:

  1. Multivalent Ag induces ______
  2. High concentrations of Ag induce ________
  3. Low concentrations of Ag induce ________
A
  1. B cell death
  2. B cell death
  3. functional anergy (decrease membrane Ig)
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25
Q

Nature and concentration of self Ag determine the fate of B cells. For example:

  1. Multivalent Ag induces ______
  2. High concentrations of Ag induce ________
  3. Low concentrations of Ag induce ________
A
  1. B cell death
  2. B cell death
  3. functional anergy (decrease membrane Ig)
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26
Q

What is peripheral tolerance and where does it occur?

A

It is the mechanism by which mature T cells that recognize self antigen in peripheral tissues become incapable of responding to these antigens.

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27
Q

What are the four mechanisms of peripheral tolerance?

A
  1. Clonal Deletion
  2. Clonal Anergy
  3. Suppression
  4. Ignorance
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28
Q

What is clonal deletion?

A

A mechanism of peripheral tolerance through which the cells are eliminated by induced cell death

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29
Q

What is clonal anergy?

A

A mechanism of peripheral tolerance through which the mature cell is present but is functionally inactivated.

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30
Q

True or False: Clonal anergy is an irreversible mechanism of peripheral tolerance.

A

False.

Anergy can be REVERSED

31
Q

Suppression is a mechanism of peripheral tolerance through which cellular activity is inhibited due to interaction with ______.

A

Other Cells such as T Regulatory Cells:
CD4/CD25 T Cells
IL-10 Secreting Regulatory Cells

32
Q

The co-existence of self-reactive clones and antigen in which the cells do not respond to antigen is known as _____.

A

Ignorance (mechanism of peripheral tolerance)

33
Q

The co-existence of self-reactive clones and antigen in which the cells do not respond to antigen is known as _____.

A

Ignorance (mechanism of peripheral tolerance)

34
Q

What kind of factors will determine which mechanism(s) of peripheral tolerance are operative?

A
  • concentration of self antigen in generative organs
  • affinity of receptor for antigen
  • nature of antigen
  • concentration of costimulatory molecules
35
Q

How do T cells affect the outcome of B cell activation in the periphery?

A

There must be a coordinated response (two signal hypothesis):
Signal 1 = signal through Ag receptor
Signal 2 = signal mediated through CD40-CD40L
Cytokines released = antibody production

36
Q

The “two signal hypothesis” for B cell Activation in the periphery states that the absence of one signal would results in ______.

A

B cell anergy

37
Q

Typically, APC will attach to Naive T cells through MHC and costimulatory molecules B7 and ______.

38
Q

Which molecule will compete with costimulatory CD28 for B7?

39
Q

APC that recognize foreign antigen will attach to T cells through MHC and costimulatory molecules B7- ______.

40
Q

Which molecule will compete with costimulatory CD28 for B7 when APC recognize self-antigen?

41
Q

Anergic cells show a block in _____-induced signal transduction via lack of costimulation by _____ and inhibition by ______.

A

TCR
B7
CTLA-4

42
Q

What does CTLA-4 bind to?

43
Q

If a T cell recognizes self antigen, there will be an engagement of inhibitory receptors (such as CTLA-4) that will make the T cell _______.

A

Unresponsive (anergic)

44
Q

Peripheral tolerance via apoptosis results in deletion of self-reactive cells through cytochrome c + caspase-9 (neglect) or through Fas-____+Caspase-___ (activated death).

45
Q

IL-10 inhibits functions of _____, such as IL-12 secretion or B7 expression.

46
Q

TGF-beta inhibits _______ cell proliferation.

47
Q

IL-4 inhibits actions of _______.

48
Q

IL-10 inhibits ______ activation.

A

macrophage

49
Q

How does ignorance happen?

A
  1. Antigen is expressed in a privileged site (brain) or sequestered (formed cyst) where the T cells cannot reach the antigen due to inability to cross some endothelial barrier.
    or
  2. Antigen is not expressed in the context of MHC
50
Q

Foreign antigens may be administered in ways that preferentially _________ rather than immune responses.

A

induce tolerance

51
Q

Foreign antigens may be administered in ways that preferentially _________ rather than immune responses.

A

induce tolerance

52
Q

________ antigens administered subcutaneously or intradermally with adjuvants will favor immunity rather than tolerance.

A

Protein

*adjuvants enhance the bodies response to antigens

53
Q

High doses of antigens administered systemically without adjuvants tend to induce ______ rather than ______.

A

Tolerance rather than immunity

54
Q

Oral administration of antigen will favor ________ induction.

55
Q

A state of immune _____ follows oral administration.

A

Hyporesponsiveness (maintains homeostasis so there is no immune response to food antigen)

56
Q

A low dose of orally administered Ag will _____ Th2, whereas a high dose will cause _______ or _______ of Th1 and Th2 cells.

A 
low= induction of Th2
high= deletion or anergy of Th1/Th2
57
Q

For both B lymphocytes and T lymphocytes, anergy is associated with _____tolerance and apoptosis is associated with ______tolerance.

A

Peripheral

Central

58
Q

How does central and peripheral tolerance relate to the development of autoimmunity?

A

Autoimmunity results when central and peripheral tolerance is broken
-The immune system is dysregulated and attacks the organs it was designed to protect

59
Q

True or False: Autoimmune diseases only involve the nervous, gastrointestinal, and endocrine systems.

A

False.

Autoimmune diseases can involve almost every organ system

60
Q

What are the seven common factors that can predispose an individual to autoimmune diseases?

A
  1. MHC associations
  2. Familial concordance
  3. Gender (females)
  4. Climate (equatorial range)
  5. Chemical agents
  6. Infectious agents
  7. Immune dysregulation
61
Q

Certain ______ occur at higher rates within the MHC haplotypes of autoimmune individuals but no one has the same exact halplotype.

62
Q

______ hormones represent an important modulatory factor in the autoimmune response.

63
Q

Pregnancy causes a switch to more _____ production which makes MS better and Lupis worse.

A

Th2
MS: associated with increases in Th1
Lupis: associated with increases in Th2

64
Q

What initiates an autoimmune response?

  1. Incomplete ________
  2. Stimulation of normally ______ self reactive cells
  3. Altered ______ of anergic cells
A
  1. deletion of self reactive cells
  2. anergic
  3. regulation
65
Q

What initiates an autoimmune response?

  1. Incomplete ________
  2. Stimulation of normally ______ self reactive cells
  3. Altered ______ of anergic cells
A
  1. deletion of self reactive cells
  2. anergic
  3. regulation
66
Q

Molecular mimicry occurs when microbial antigen peptide within the MHC ______.

A

Appears like self-antigen

67
Q

What is “bystander activation” in the context of autoimmunity?

A

Antigen presenting cell with self-antigen comes into close proximity of a microbe. The microbe activates APC expression of costimulatory molecules (B7-CD28) and T cells attack self tissue.

68
Q

Autoimmune disease may be either ______ or ______ specific.

A

Systemic

Organ

69
Q

Lupus Erythematosus (SLE) and Rheumatoid Arthritis are _____ autoimmune diseases. Multiple sclerosis and Insulin Dependent Diabetes Mellitus are ______ autoimmune diseases.

A

Systemic

Organ-specific

70
Q

Lupus Erythematosus (SLE) and Rheumatoid Arthritis are _____ autoimmune diseases. Multiple sclerosis and Insulin Dependent Diabetes Mellitus are ______ autoimmune diseases.

A

Systemic

Organ-specific

71
Q

What is the most common inflammatory disorder of the central nervous system?

A

Multiple Sclerosis (MS)

72
Q

What is characterized as a “T cell mediated autoimmune disease in which T cells are specific for components of the myelin sheath” ?

A

MS (damage to CNS via myelin degradation)

73
Q

True or False: An individual may develop more than one autoimmune disease.

74
Q

True or False: An individual with Lupus may also develop MS.

A

False: These diseases are contradictory. Lupus (Th2), Multiple Sclerosis (Th1)

Sp 15-Micro Final (12 decks)

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