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Immuno Exam 3 > Tolerance and Immunology > Flashcards

Tolerance and Immunology Flashcards

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1
Q

Tolerance

A

process by which the body ensures that immune responses are directed against foreign antigens and altered self and not against normal self tissues

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2
Q

Tolerance definition

A

SPECIFIC unresponsiveness of an individual to an antigen

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3
Q

Which cells are capable of tolerance

A

only cells with antigen-specific receptors can be tolerant… B and T cells

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4
Q

Tolerance mechanism involves

A

the selective destrcution of lymphocytes that react to self antigens (positive and negative selection)

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5
Q

Central tolerance

A

occurs early in lymphocyte development

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6
Q

Peripheral tolerance

A

regulation of “escapees” of central tolerance in the periphery

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7
Q

Central B tolerance

A

if an immature B cell possesses an IgM that is self-reactive it will undergo anergy (tolerant signals) ro deletion (apoptotic signals)

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8
Q

Peripheral B cell Tolerance

A

BCR is constantly stimulated, chronic stimulation in the absence of other secondary signals = anergy

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9
Q

Central T cell Tolerance

A

if an immature T cell possesses a TCR that is strongly self-reactive, apoptosis is induced

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10
Q

Peripheral T cell Tolerance

A

Primary stimulation of Tcells (antigen recognition) without secondary stimulation results in an inactive T cells

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11
Q

Primary stimulation of peripheral T cells

A

antigen recognition via MHC/peptide-TCR

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12
Q

Secondary stimulation of peripheral T cells

A

B7-CD28 stabilizes IL-2 mRNA that is otherwise rapdily degraded

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13
Q

Antigen recognition without _____________ results in

A

IL-2 present results in peripheral T cell anergy

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14
Q

Repeated stimulation of activated T cells results in

A

apoptosis (clonal deletion)

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15
Q

Regulatory T cells

A

inhibits the activation of T cells by self peptide/MHC

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16
Q

Peripheral Tolerance via regulatory B cells

A

produce IL-10 that negatively regulates the activation of both Th1 CD4+ T cell and CD8+ T cells

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17
Q

Peripheral Tolerance via regulatory T cells

A

CD4+ usually (may be CD8+), express FoxP3, secrete inhibitory cytokines (TGF-beta, IL-10 for Th1 inhibition) and CTL lysis

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18
Q

FoxP3

A

transcriptional repressor expressed by T reg and B reg cells

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19
Q

relapsing MS patients show

A

decreased numbers of IL-10 producing B cells and decreased ability of existing cells to produce IL-10

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20
Q

What age groups are consider immunosuppressed

A

very young and elderly

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21
Q

malnutrition may

A

play a profound effect on the immune system

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22
Q

Disease

A

some diseases may induce a state of nonresponsiveness to antigens

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23
Q

Stress

A

profoundly affects the immune system

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24
Q

HLA sequence

A

determines whether a individual will be capable of responding to an antigen sequence

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25
HLA-B27
HLA sequence that causes autoreactivity producing ankylosing spondylitis and reactive arthritis
26
Doasge and tolerance
small doses over long periods induce tolerance
27
If self molecules are located in immunologically privileged sites and trauma occurs
the immune system may gain access to "new" antigens evoking a response
28
Sympathetic opthalmia
retinal or uvealproteins exposed after trauma to eye
29
Genetic predisposition to autoimmunity
HLA type inheritance
30
Preceding infectious processes in autoimmunity
molecular mimicry from a pathogens antigens causes cross-reacting immune-responses
31
Streptococcal pharyngitis --> which autoimmune disease?
rheumatic fever and heart valve destruction
32
Helicobacter pylori --> which autoimmune disease?
gastric carcinoma
33
Campylobacter jejuni --> which autoimmune disease?
Guillian-Barre syndrome
34
What is Guillian-Barre syndrome
immune response against the pathogens LPS that cross-reacts with motor nerves, resulting in severe paralysis and polyneuritis
35
Klebsiella --> which autoimmune disease?
ankylosing spondylitis (chronic inflammation, fibrosis, and ossification of the articulations)
36
Diseases that elicit polyclonal activation of lymphocytes act via
activation of previously anergic self-reactive lymphocytes
37
What factors are linked to autoimmune diseases?
genetics, previous infection, environmental trigger,impaired immunoregulatory mechanisms, hormones/gender
38
Environmental triggers linked to autoimmune diseases?
exposure to environmental triggers (ie. gluten)
39
Exposure to gluten may lead to
Celiac Disease
40
What is Celiac Disease
exposure to gluten causes autoimmune attack on villi in the small bowel (villi atrophy and T cell infiltration)
41
Celiac Disease is mediated by
T cells
42
95% of individuals with Celiac Disease have
autoantibodies against tissue transglutaminase (anti-TG)
43
90% of individuals with Celiac Disease have
HLA-DQ2 and remaining have HLA-DQ8
44
Celiac Disease is associated with
IgA deficiency
45
Impaired immunoregulatory mechanisms that lead to autoimmune diseases
deficient or defective T cells may alter normal immune control, defective antibody production of one class may lead to inhibition of another class
46
Example of defective antibody production of one class may lead to inhibition of another class
elevated IgE in selective IgA deficiency
47
Which gender is more likely to have an autoimmune disease and why
women, possibly due to ER on immune cells
48
Myasthenia Gravis is a result of
antibodies produced against the ACh receptors at neuromuscular junctions (ORGAN-SPECIFIC)
49
Myasthenia Gravis manifestations
severe muscle weakness, drooping eyelids, difficulty chewing, swallowing, breathing
50
Myasthenia Gravis genetic component
associated with HLA-DR3
51
Myasthenia Gravis
Organ-specific, antibody-mediated
52
Autoimmune hemolytic anemia is the result of
antibodies produced against either Rh antigen or I antigens on RBCs, targetting them for destruction
53
RBCs in Autoimmune hemolytic anemia
complement-mediated lysis or macrophage phagocytosis
54
Autoimmune hemolytic anemia effects which body system
spleen (organ-specific)
55
Autoimmune hemolytic anemia manifestations
anemia, haemolysis, low haptoglobin, increased lactate DH, elevated direct bilirubin
56
Myasthenia gravis is a Type ____ hypersensitivity
Type II
57
Direct antiglobin would test positive in which disease
Autoimmune hemolytic anemia
58
Autoimmune hemolytic anemia is caused by
warm hemagluttinins or cold hemagluttinins
59
Warm hemagluttinins
IgG that can bind RBCs at 37C specific for Rh (Kupffer phagocytosis)
60
Cold hemagluttinins
IgM binds RBCs at less than 37C specific for I antigens (complement/MAC)
61
Systemic Lupus Erythematosus
antibodies against double-stranded DNA (and other nuclear/cytoplasmic components) form IC and deposit in kidneys, arteriole walls, synovium
62
Systemic Lupus Erythematosus IC's activate
complement, PMNs, granulocytes
63
Systemic Lupus Erythematosus manifestations
fever, joint pain, malar, CNS damage, damage to heart and kidneys
64
genetic component of SLE
C1, C4, or C2 deficiency resulting in lack of C3b for IC phagocytosis
65
Systemic Lupus Erythematosus is more common in what patient population
women 15-45
66
is linked to what HLA type
HLA-DR3 or DR2
67
Tests for Systemic Lupus Erythematosus
indirect fluorescent antibody stain
68
Scleroderma
antibody production against nuclear enzymes (topoisomerase and RNA pol)
69
Scleroderma manifests as
skin thickening, arthritis, hair loss, arteritis, Reynaud's, overproduction of EC matrix proteins
70
Scleroderma is most common in what patient population
women 30-50
71
Sjogren's Syndrome
antibodies against cytoplasmic protein-RNA complexes called SS-A (Ro) and SS-B (La)
72
Detection of Scleroderma
indirect fluorescent antibody stain (same as SLE) but different pattern
73
Sjogren's Syndrome manifestation
systemic inflammation and destruction of exocrine glands, esp salivary and lacrimal - dry mouth and eyes
74
Sjogren's Syndrome detection
ELISA or western
75
SLE is a Type _____ hypersensitivity
Type III
76
Graves' Disease
antibodies (TSI) against TSH receptors, bind and cause expression of TSH receptor = hyperthyroidism
77
Graves' Disease Manifestations
low TSH, high T4 and T3
78
TBIIs
antibodies aginst TSH receptors, bind and cause repression og TSH receptor = hypothyroidism
79
Graves' Diseaseeffects primarily
women (4:1)
80
Goodpasture's Disease
antibody production against alpha-3 chain of basement membrane collagen, Fc binds Fc-gamma receptors on immune cells for activation
81
Goodpasture's Disease manifestations
binding to renal glomeruli, pulmonary alveoli causing disease and tissue injury
82
Goodpasture's Disease is a Type _____ hypersensitivity
Type II
83
Multiple Sclerosis
T-cell mediated (CD4 and CD8) response to CNS myelin
84
MS may be linked to
EBV, ADV-2, Hep-B infections, and associated with HLA-DR2
85
Type I DM
T-cell mediated- CD8 CTLs destroy insulin-producing beta cells of the pancreas
86
Genetic component to Type I DM
HLA-A2
87
Rheumatoid Arthritis
T-cell mediated and antiboy mediated
88
Inflammation in RA in initiaed by
deposition of IC's and inflammaotry infiltration of the synovial membrane
89
What immune cells are present in RA synvoial membranes
macrophages, T cells, and plasma cells
90
RA manifestations
chronic inflammation of the synovium, fever, fatigue, joint pain and swelling
91
Pannus
destruction of neighborign cartilage to expose chondrocytes and compromise synvoial integrity
92
2 diagnostic markers for RA
anti-citrullinated peptide antibodies (ACPAs) and rheumatoid factor (RF)
93
RF
IgM against IgG Fc portions, form IC's that are deposited in the synovium --> complement
94
RF titers
20-30% of the time, no RF in RA patients, but generally RF levels coincide with RA severity
95
presence of RF and arthritis
not always due to RA, RF may be elevated in SLE
96
ACPA titers
90-95% indication of RA
97
Hashimoto's thyroiditis
T cell-mediated, but have antibodies against thyroid peroxidase and thyroglobulin
98
What type of hypersensitivity is Hasimoto's?
Delayed Type IV
99
Hashimoto's thyroiditis manifestations
puffy round face, dry skin, cold, brittle hair and nails
100
Hashimoto's thyroiditisis associated with
HLA-DR5, -Dr3 and B8
101
Treatment for hypothyroidism
administration of thyroxine
102
Myasthenia Gravis treatment
cholinesterase inhibitors
103
immunosuppressive therapy for autoimmune disease
anti-mitotic drugs, anti-inflammatory, cyclosporine
104
advantages and disadvantages of using immunosuppressive therapy for autoimmune disease
dampen immune response, adverse side effects (susceptibility of disease), NSAIDS
105
Cytokine treatment of MS
IFN-beta.1a (avonex, rebif)
106
TNF-alpha blockades (infliximab, etanercept, adalimumab, golimumab, certolizumab
treatment for RA and akylosing spondylitis
107
SLE and scleroderma treatments
bone marrow ablation and transplant
108
glatiramer acetate
induces production of Treg cells for treatment of MS
109
tocilizumab
tocilizumab for RA Anti-IL-6R
110
rituximab
anti-CD20 for B cell targeting
111
abatacept
T cell activator for RA
112
natalizumab
anti-alpha-4 integrins for MS
113
Anti-BAFF
SLE
114
Low dose - Oral tolerance
oral low dose Ag causes induction of Th3 cells and the release of TGF-beta which inhibits Th1 and Th2
115
Low dose - Oral tolerance results
ag-specific Th3 and IgA isotype switch (inhibits Th1 and Th2 and cytokine production)
116
High dose - Oral tolerance
clonal exhaustion and anergy of CD4 T cells
117
Oral tolerance for MS
bovine myelin
118
Oral tolerance for RA
Type II collagen
119
Oral tolerance for graft rejection
HLA molecules

Immuno Exam 3 (6 decks)

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