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CMBM exam 4 > Regulation of Immune Response > Flashcards

Regulation of Immune Response Flashcards

1
Q

What autoimmune disease is associated with dry eyes and dry mouth?

A

Sjogren disease

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2
Q

Which of the following antibodies are of most use for diagnosis of pernicious anemia?

A

Anti-parietal cells

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3
Q

What is the reaction to self-antigens called?

A

Tolerance

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4
Q

Loss of self tolerance

A

autoimmune disease

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5
Q

Shift in immune responses

A

Hypersensitivity

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6
Q

Decrease in immune response

A

Immunodeficiency

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7
Q

Th0 cell is stimulated by Il-12, what occurs?

A

Differentiates to Th1 cells

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8
Q

Th0 is stimulated by IL-23 and IL-6, what occurs?

A

Th17 cells develop

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9
Q

Th0 cell is stimulated by IL-4, what occurs?

A

Th2 cells develop

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10
Q

what cytokines are produced by Th1 cells?

A

IL-2

IFN-y - activates Macrophages

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11
Q

what cytokines are produced by Th2 cells?

A

IL-4
IL-5
IL-10 and IL-13 - these are regulatory
IL-10 inhibits Th1 cells to favor a shift to humoral immunity

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12
Q

TGF-b and IL-10 induce Tregs to produce

A

more TGF-b and IL-10

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13
Q

How do Th2 cells negatively regulate Th1 cells?

A

through IL-4, IL-10 and TGF-b

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14
Q

How do Th1 cells negatively regulate Th2 cells?

A

IL-2 and IFN-y

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15
Q

Tolerance

A

specific state of unresponsiveness induced by prior exposure to an antigen

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16
Q

When is self tolerance induced?

A

in the embryonic developmental states

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17
Q

Main mechanisms of Tolerance:

A

Clonal deletion
Clonal anergy
Ignorance

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18
Q

where does natural tolerance take place?

A

Primary lymphoid organs

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19
Q

How can tolerance by induced?

A

injection of stem cells in neonatal animals

grafting of allogenic bone marrow or thymus in early life results in tolerance to donor type cells and tissues

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20
Q

factors that influence induction of tolerance

A 
physical form 
route of entry/location
Dosage 
Antigen Processing 
Age
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21
Q

Factors that stimulate the immune response

A 
large, complex molecule 
subQ, IM 
Optimal dosage
High level of costimulators 
adult
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22
Q

Factors that stimulate unresponsiveness

A 
soluble or small molecules 
Oral, IV 
very large or small amount (dosage) 
Low level of costimulators 
early age
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23
Q

Immune privilege organs

A

eye
testis
uterus

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24
Q

what axis does the CNS-immune relationship take place on?

A

H-P-A axis

hypothalamus-pituitary-adrenal gland

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25
Q

clonal anergy promoted through

A
  1. no costimulation - lack of B7/CD28 interaction
    or
  2. interaction of CTLA-4 and B7 which prevents T cell activation
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26
Q

Ignorance

A

antigen in low amounts
antigen in organs where there is no access - immune privileged
organs with enhanced immune regulation and induce tolerance through TGF-b

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27
Q

Autoimmune response in eye

A

against antigens from melanin containing structures in retina
damage to one eye causes inflam response in other eye
Granulomatous uveitis can leave person blind

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28
Q

how is peripheral tolerance achieved?

A

Anergy - through CTLA-4 and B7
Activation induced cell death - through Fas and FasL
Cytokine regulation - IL10 and TGF-b from Tregs

29
Q

T regulatory cells

A

T suppressor cells - suppress immune response
CD4+, CD25+ outside the thymus
express Fox3p
produce IL10 and TGF-b to dampen immune responses
inactivate effector cells - functionally unresponsive

30
Q

Autoimmunity

A

more common in women
genetic disposition - African american - SLE, Native Americans - scleroderma, RA
Left handed ppl slightly over right handed ppl

31
Q

Type II hypersens. - Complement mediated

A

Transfusion reaction
Eythroblastosis fetalis
certain drug reactions

32
Q

Type II hypersensitivity

A

Graft rejection

33
Q

Type II hypersensitivity - Antibody mediated cellular dysfunction

A

Myasthenia gravis

Graves disease

34
Q

Autoimmunity triggers

A

Genetic factors - asso. with HLA haplotypes, autoimmune regulator (defective thymic deletion (central)), complement deficiency, Foxp3 defect -> IPEX (x linked defect in Treg activation)
Environmental factors - drugs, hormones (estrogen), Toxins, geographic clustering
Infection: molecular mimcry* -

35
Q

Ankylosing Spodylitis HLA allotype

A

B27

36
Q

Rheumatic fever - pathogen, mimicking?

A

Strept. Pyogenes

M protein similar to molecules on Heart, skin, nerve and connective tissue

37
Q

Ankylosing spondylitis - pathogen mimicry?

A

Klebsiella Pneumoniae

38
Q

Dx of autoimmune disorders

A

symptoms
immunofluorescence
complement levels maybe decreased
biochemical assays for specific antibodies

39
Q

Treatment of autoimmune disorders?

A 
Immunosuppressive and anti-inflammatory drugs 
disease modifying drugs 
thymectomy 
plasmapheresis 
monoclonal antibodies 
but first, always treat the symptoms
40
Q

examples of systemic autoimmune disorders

A 
SLE
scleroderma 
sjogren syndrome 
Rheumatoid arthritis 
Polymyositis
41
Q

Organ specific autoimmune disease

A 
goodpasture's syndrome 
hashimoto's thyrodiditis 
grave's disease 
myasthenia gravis 
Addison's disease 
Diabetes melitus Type I
42
Q

Systemic Lupus Erythematosus

A

Type III hypersens.
chronic affecting multi organs
90% females
onset 15-50 yo
Risk factors: certain HLA types, Asian, Hormones - Estrogens
5 yr survival rate is about 95% in US and canada

43
Q

Pathogenesis of SLE

A

immune complex deposition
antinuclear antibodies against dsDNA, histone and smith-antigen
antinuclear antibodies against DNP
antiphospholipids
In general, C1, C2, C4 deficiency leading to decreased opsonization of immune complexes so there is decreased clearing
Note that Ab are not specific to Lupus

44
Q

Clinical signs of SLE

A

often called The great imitator
symptoms diverse and often non specific
Skin manifestations: butterfly malar rash*
Alopecia - loss of hair
Oral ulcers
Photosensitivity rash (raised, erythematous)
Renal - Membranoproliferative glomerulonephritis, thickening of glomerular capillary wall, end stage renal failure leads to death

45
Q

SLE - clinical signs in MS, pulmonary, neurological, cardiac systems

A

joint pain, muscle pain, no destruction of joints
SLE pneumonitis, pleuritis
cognitive, headache, seizures, neuropathies
Verrucous endocarditis (libman-sacks) -depostis around valves
pericarditis
antiphopholipid antibody syndrome (thrombotic disorder) leads to PTT

46
Q

DX of SLE

A

Elevated ESR
decreased C3 and C4 levels
fluorescent antinuclear antibody
LE cells (not specific though)

47
Q

Treatment of SLE

A

anti inflammatory drugs to prevent swelling and inflammation
immunosuppressants - azthioprine, methotrexate, cyclophosphamide

48
Q

Rheumatoid Arthritis

A

autoimmune disease of the joints
Autoantibodies to cartilage
Rf has receptor for Fc portion of IgG
Immune complex formation leads trigger of complement

49
Q

Clinical signs of RA

A

Joint pain - small joints and symmetric
Inflammation
Stiffness - usually in morning
keratoconjuctivitis

50
Q

Diagnosis of RA

A

ESR and C reactive protein but these are non specific
Rheumatoid factor usually IgM, IgG and IgA
clinical manifestations
Radiological findings

51
Q

Sjogren’s syndrome

A

Type III hypersens rxn
Progressive autoimmune (immune complex) disorder
destruction of lacrimal and salivary glands
Antiribonucleoprotein antibodies SS-A and SS-B

52
Q

Clinical signs of Sjogren’s

A

xerostomia - dry mouth
unilateral parotiditis
xerophthalmia

53
Q

Diagnosis of sjogren’s

A

schirmer’s test - filter paper to collect and measure tear production
SSA/Ro or SSB/La detection

54
Q

Treatment of Sjogren’s

A

Anti inflammatory medications
Artificial tears
NSAIDs and disease modifying drugs

55
Q

Goodpasture’s syndrome

A

Type III hypersens.

Autoantibodies against a3 chain of collagen IV in pulmonary and glomerular basement membrane

56
Q

Reiter’s syndrome

A

mostly in males
Arthritis, Non gonococcal urethritis or cervicitis
Conjuctivitis

57
Q

Risk factors for Reiter’s syndrome

A

positive for HLA-B27

shigella, yersinia, salmonella and chlamydia

58
Q

Ankylosing spondylitis

A

Chronic autoimmune disorder of vertebrae
affects the vertebrae and sacroiliac joints
mainly in males
Symptoms: inflammation and stiffness of lower back
Risk factor: HLA-B27 and Klebsiella infections

59
Q

Multiple Sclerosis

A

autoimmune neurological demyelinating defect
autoreactive cells against Myelin Basic protein (MBP)
mediated by Th17 cells

60
Q

Symptoms of MS

A 
slurred and slow speech 
blurred vision - often in one eye 
difficulty swallowing 
loss of bladder control 
loss of sensation 
MRI of brain and spine shows areas of demylenation
61
Q

risk factors of MS

A

more common in high altitudes
more common in females
syphillus - tertiary
Measles and Herpes virus

62
Q

Myasthenia Gravis*

A

Type II hypersensitivity
autoantibodies binding Ach receptors
blocks Ach binding leads to inhibition Ach at neuromuscular junction

63
Q

Symptoms of Myasthenia Gravis

A

progressive muscle weakness
easy fatigability
blurred vision
difficulty swallowing and breathing

64
Q

Diagnosis and treatment of Myasthenia Gravis

A

Dx - Acythylcholiesterase inhibitor (edrophonium), enlarged thymus
Tx - cholinesterase inhibitors, thymectomy

65
Q

Graves disease

A

type II
Autoantibodies against TSH receptors in the thyroid - tricking thyroid into releasing more hormone
leads to hyperthyroidism and goiter

66
Q

Symptoms of Graves disease

A 
Tachycardia 
Weight loss 
agitation and irritability 
Pretibial myxedema - kids 
exophthalmos (propotosis)
67
Q

Hashimoto’s Thyroiditis

A

Type II and IV
Autoantibodies -thyroid peroxidase and thyroblobulin
Gradual destruction of Thyroid gland - hypothyrodism

68
Q

Clinical signs of Hashimoto’s Thyroiditis

A 
Painless symmetric goiter 
weight gain and cold tolerance 
depression and fatigue 
dry and coarse hair 
bradycardia
69
Q

Insulin dependent diabetes Mellitus

A

HLA-DR3 and HLA-DR4
Early: autoantibodies against beta cells
later: mediated by T lymphocytes (mostly cytotoxic)
Early sudden onset

CMBM exam 4 (27 decks)

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