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Immunology PY2 > Lecture 30: Autoimmunity & Autoimmune Diseases > Flashcards

Lecture 30: Autoimmunity & Autoimmune Diseases Flashcards

1
Q

autoimmune disease happens when antigen-specific immunity targets _____ proteins

A

self

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2
Q

autoimmunity is generally a failure of _____ and ____ tolerance

A

central and peripheral

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3
Q

what effects can autoimmune diseases have on organs?

A

can damage them and when they try to repair themselves, it often leads to fibrosis or desposition of inflexible tissue that interferes with normal function

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4
Q

what does it mean if an autoimmune dx is organ-specific? What about if its systemic?

A

Organ Specific: the target antigen is unique to a given organ
Systemic: The autoimmune response is to a broad range of self-antigens

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5
Q

what are the 3 main ways autoimmune dx happen?

A
  1. autoreactive T cells and cell-mediated immune responses
  2. autoantibodies
  3. sometimes both
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6
Q

autoimmune dx affect ___% of the population

A

8

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7
Q

autoimmune dx are more common in what sex?

A

femail

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8
Q

what are2 reasons why females may have a higher chance of autoimmune dx?

A
  1. tendency of women to mount more robust innate & adaptive immune responses (except during pregnancy)
  2. immune-enhancing effects of estrogen (androgens promote immune suppression)
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9
Q

during pregnancy, Th__ responses are favoured rather than Th__

A

2; 1

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10
Q

what types of autoimmune dx may be worsened by pregnancy? Which ones may be ameliorated?

A

Th2 dx like SLE may be worsened; Th1 like MS may be improved

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11
Q

what are the immune effector cells in Type 1 DM?

A

Th1 cells and autoantibodies

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12
Q

what are the target of Myasthenia gravis?

A

acetylcholine receptors

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13
Q

what are the effectors of myasthenia gravis?

A

auto-antibodies (blocking)

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14
Q

what are the targets of MS?

A

brain or white matter

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15
Q

what are the effectors of MS?

A

Th1 and Tc cells and auto-antibodies

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16
Q

what are the targets of rheumatoid arthritis?

A

connective tissue, IgG

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17
Q

what are the effectors of rheumatoid arthritis?

A

auto-antibodies, immune complexes

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18
Q

what are the targets of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

A

Multiorgan/loss of FoxP3 gene

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19
Q

what are the targets of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

A

missing regulatory T cells

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20
Q

what are the targets of autoimmune polyendocrine syndrome type 1 (APS-1)

A

multiorgan loss of AIRE gene

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21
Q

what are the effects of autoimmune polyendocrine syndrome type 1 (APS-1)

A

defective central tolerance

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22
Q

In organ-specific autoimmune dx, ____ and ____ bind to cell membrane antigens, causing cell lysis and/or an inflammatory response that damages the target organs

A

lymphocytes or auto-antibodies

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23
Q

why is organ-specific localized to only that specific organ?

A

bc the antibodies/T cells bind only to the antigens present in that region

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24
Q

what are the target antigens of vitiligo?

A

melanocyte antigens

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25
Q

what is the immune pathology of Type 1 diabetes?

A

caused by cell-mediated autoimmune response to pancreatic beta cells in the islets of langerham. Activated CTL attack the beta cells, IFN-y, IL-1 and TNF-a are produced, leading to a DTH response . Autoantibodies may also contribute to islet cell destruction

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26
Q

what are the Sx and outcomes of Type 1 diabetes?

A

glucose metabolism is disrupted, leading to impeded blood flow, kidney failure, blindness, and death if untreated

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27
Q

what is the immune pathology of myasthenia gravis?

A

results from production of auto-antibodies directed against acetyl choline receptprs (AChR) on the motor end plates of muscles

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28
Q

what are the signs and outcomes of myasthenia gravis?

A

fatgable weakness and progressive weakening of structural muscles and evential death of ACh-R bearing cells. Severity ranges from droopy eyelid to life-threatening breathing difficulties due to myasthenic crisis

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29
Q

what is the treatment of myasthenia gravis?

A

removal of antibodies by plasmapheresis, suppression of B cell activation with corticosteroids and/or using cholinesterase inhibitors to increase Ach level

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30
Q

the hallmark of systemic autoimmune dx is damage throughout the body, which can present as _____ or ______

A

cell mediated immune reactivity or deposition of antibody-antigen complexes (or both)

31
Q

what are some examples of systemic autoimmune Dx?

A

MS, SLE, RA

32
Q

what is the immune pathology of Rheumatoid arthritis (RA)?

A

multifactorial, caused by autoantibodies of the IgM class (rheumatoid factor) that react with Fc of self IgG. The IgM/IgG complexes deposit in the synovia of the joints where complement is activated

33
Q

what are the symptoms of RA?

A

chronic inflammation of the joints characterized by granulocyte/monocyte infiltration, cartilage/collagen destruction by hydrolytic enzymes, fibrin deposition and joint dysfunction

34
Q

what are the outcomes of RA?

A

Can lead to life-threatening severities if left untreated, including cardiac involvement

35
Q

what are the treatments for RA?

A

corticosteroids (to globally reduce immune activity), DMARDs, biologics (i.e. antibodies against TNF, IL-1B and IL-6 or the IL-6 receptor)

36
Q

what is the immune pathology of MS?

A

demyelination of CNS nervous system tissue driven by CD4+ Th17 cells that attract & activate macrophages, leading to damage of nerve fibers, autoreactive CTL and antibodies

37
Q

what are the symptoms of MS?

A

numbness, vision loss, paralysis, bladder & bowel dysfunction

38
Q

t/f the recovery from MS attacks can be partial or complete

A

t

39
Q

what are the outcomes of MS?

A

dictated by the degree of disease activity, location of attacks and dx-modifying therapies

40
Q

what are the treatments for MS?

A

drugs to prevent lymphocyte egress into CNS, sequestration in lymphoid organs, anti-inflammatory agents, T & B cell depleters

41
Q

_____ is a rodent model of central nervous tissue inflammation resembling MS in which T cell tolerance to myelin basic protein (MBP) or proteolipid protein components of the myelin sheath is broken by immunization with MPB in complete Freud’s adjuvant

A

experimental autoimmune encephalomyelitis (EAE)

42
Q

autoimmune polyendocrine syndrome type-1 (APS-1) results from mutations in the ____ gene

A

AIRE

43
Q

what is the purpose of the AIRE gene?

A

codes for AIRE transcription factor that allows tissue-specific antigens to be expressed in the thymus

44
Q

what is the significance of the AIRE transcription factor allowing tissue specific antigens to be expressed in the thymus?

A

ensures elimination of autoreactive T cells and selection of Treg cells

45
Q

immune dysregulation, polyendrocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by mutations in the _____ gene associated with ___ and ___ cells

A

FoxP3; tTreg cells & pTreg cells

46
Q

AIRE and IPEX impact multiple organs and are characterized by what effects?

A

endocrine dysfunction, autoimmunity & primary immunodeficiencies resulting from disruption of immunologic homeostasis

47
Q

autoimmune dx are often associated with expression of ___ molecules with certain allelic specificities

A

HLA

48
Q

people with HLA-B27 are 100x more likely to develop _____ than people who have a different HLA-B allele

A

alkylosing spondylitis (autoimmune dx involving inflammtion of the vertebrae)

49
Q

autoimmune dx are associated with preferential expression of certain TCR ____ region genes and mutations in ____ or ___ genes involved in establishing/maintaining tolerance

A

variable; AIRE or IPEX

50
Q

people with ___ Treg cells, ____ TCR and MHC molecules capable of binding ____ will be susceptible to autoimmune dx

A

dysfunctional/low; autoreactive; self-peptides

51
Q

inflammation-promoting environmental and/or lifestyle factors predispose people to autoimmune dx. Give some examples of these exposures

A

gum dx, smoking, vitamin D exposure

52
Q

t/f infections and altered gut microflora are also complicated by induction of autoimmunity

A

t

53
Q

in most cases, organ-specifc and systemic autoimmune dx is linked to what type of T cells?

A

autoreactive CD4+ T cells

54
Q

aside from autoreactive CD4+ Tcells, what other T cells are involved in autoimmunity?

A

Th17 and Th1

55
Q

what is the role of Th17 cells in autoimmunity?

A

produce Il-17 and IL-23

56
Q

what is the role of Th1 cells in MS?

A

myelin basic protein (MBP)-reactive Th1 clones transfer autoimmune encephalomyelitis (EAE) to healthy mice

57
Q

what is the role of Th2 cells in MS?

A

MBP-reactive Th2 cells prevent EAE induction by immunization with MBP

58
Q

t/f many mechanisms for generation of autoimmune dx have been proposed. They are not mutually exclusive and any one or multiple could contribute

A

t

59
Q

what are 4 proposed mechanisms of autimmunity?

A
  1. release of sequestered autoantigens
  2. inappropriate expression of MHC class II molecules and costimulation
  3. polyclonal B cell activation
  4. molecular mimicry
60
Q

explain the “release of sequestered autoanitgens” theory of autoimmunity

A

accidental exposure of the immune system to autoantigens that are normally sequestered from immune cells are not negatively selected during development (i.e. lens protein, myelin basic protein)

61
Q

explains the “inappropriate expression of MHC class II molecules and co-stimulation” theory of autoimmunity

A
  1. IFN-y production in response to trauma/viral infection can promote autoimmune dx by inducing class 2 MHC expression by unusual cells
  2. IFN-y also promotes IL-1, which can costimulate autoreactive T helper cells that react to the autoantigen in the MHC2
62
Q

what are 4 examples of polyclonal B cell activators?

A
  1. LPS
  2. Gram-negative bateria
  3. cytomegalovirus
  4. Epstein Barr virus
63
Q

polyclonal B cell activation can cause auto-antibodies of what class? They are secreted in the absence of ___ cells

A

IgM; autoreactive T helper cells

64
Q

explain the “molecular mimicry” theory of autoimmunity

A

certain pathogens express molecules that closely resemble self-antigens and can therefore induce autoimmunity

65
Q

many viral peptides are homologous with certain self antigens, such and ____ (virus) and ____ (self-antigen)

A

measles virus P3 & myelin basic protein (MBP)

66
Q

____ type infection may be an initiating factor for development of some autoimmune dx

A

viral

67
Q

explain plasmapheresis as a treatment for autoimmune dx

A

removes autoantibodies and immune complexes from the plasma & may provide temporary relief form sx of autoantibody-mediated autoimmune dx such as RA and myasthenia gravis

68
Q

what is the role of immunosuppressive drugs like cyclosporin A in autoimmunity?

A

reduce severity of T-cell mediated autoimmune dx but leave the patient at greater risk for infection or cancer

69
Q

antibodies that deplete ____ or ____ cells, or that target ____ molecules can reduce the sx of some autoimmune dx

A

T or B cells; chronic inflammatory molecules like TNF-a and adhesions molecules

70
Q

oral administration of potential autoantigens such as myelin basic protein has been shown to induce ___ . How?

A

tolerance in animal models of dx, possibly by induction of pTreg cells that make immunosuppressive TGF-beta

71
Q

targeted treatments can involve what 2 things?

A
  1. peptide blockage of TCR that recognize self-antigens/class 2 MHC
  2. give MAB that target activated autoreactive T cells
72
Q

what MAB can be used in targeted therapy?

A

antibodies against the CD25 subunit of the high affinity IL-2 receptor

73
Q

targets immunotherapy by vaccinating with autoreactive T helper cells has the potential to induce ____ antibodies that suppress the activity of dx-causing ____ cells, while sparing ____ cells

A

anti-TCR antibodies; autoreactive T cells; T cells with other antigenic specificites

Immunology PY2 (20 decks)

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