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lect 16 Flashcards

1
Q

where is AIRE expressed

A

in lymphoid organs

thymic epithelial cells- positive selection

dendritic cells- negative selection

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2
Q

what results from the absense of AIRE in humans

A

autoimmune polyendocrine syndrome

APS-1

bc central tollerance missing

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3
Q

what are antigens that we have a tolerance to called

A

tolerogen or tolerogenic antigen

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4
Q

what are the mechanisms of central B cell tolerance

A

deletion- apoptosis
receptor editing
anergy
ignorance

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5
Q

B cell central tolerance +++ strength

A

apoptosis

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6
Q

B cell central tolerance + strength

A

anergic cell

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7
Q

B cell central tolerance +/- strength

A

mature B cell that is clonally ignorant

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8
Q

B cell central tolerance - strength

A

mature B cell

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9
Q

what happnes to the escapees of central tolerance

A

anergy due to no costimulatory singnal

deletion- FAS/FASL interactions - activates induced cell death

involves regulatory and supressor T cells

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10
Q

self rective B cells generated

A

druing immune reaction bc of SHM in gernal centre (affinity maturation)

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11
Q

what is the molecular basis of B cell anergy

A

B cells get only signal 1 from the antigen leading to anergy

follicular exclusion

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12
Q

what is follicular exclusion

A

cells excluded
from B-cell follicles in spleen &
LN; don’t receive survival signals
(die by neglect)

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13
Q

molecular basis of T cell anergy

A

only get one signla from Ag leading to anergy and no expression of IL2

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14
Q

Deletion of auto-reactive active T lymphocytes in the
periphery is due to

A

activation of the FAS receptor

ACID
activation induced cell death

anergic B cells also express Fas and can be eliminated this way

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15
Q

what disease results from mutated Fas

A

ALPS

autoimmune lymphoproliferative syndrome

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16
Q

mice with Fas and FasL mutations

A

lps and gld mice

autoimmune disease with increase numbers of lymphocytes

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17
Q

what initiates oral tolerance

A

encounter of food antigens with GALT- Ags enter circulation and presented by APC to T cell in absence of costiumulation by APC or B7

leads to T cell anergy

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18
Q

what plays an important role in oral toelrance

A

gut microbiome

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19
Q

what is the etiology of autoimmune diseases

A

genetic factors
environmental
interaction of genetic and environmental factors
drug and hormonal triggers

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20
Q

what are the genetic factors of autoimmunity

A

family clustering
- polygenic
-MHC(HLA) associated
-non HLA genes

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21
Q

what are the enviromental factors of autoimmunity

A

microbial and truama

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22
Q

what is associated genetically with autoimmune diseases

A

HLA types and Sex

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23
Q

environmental susceptibility types

A

sequestered Ags
molecular mimicry
polyclonal activation
innaproperiate expression class II MHC

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24
Q

what are the immunoprivelaged sites

A

eyes
testes
ovaries
placenta

dont develop a classical immune response

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25
what sites are autoantigens protected
cartilage neuronal antigens
26
what causes antigens to be released from immunoprivelaged sites
physical disruption OR infection
27
explain molecular mimmickry
a normally self reactive B cell wont activate from self antigen bc it wont have T cell help if a B cell is reacting to microbial antigen that looks like our own, itll have T cell help and then produce antibodies that will react to our own antigens
28
explain polyclonal activation
Lypopolysaccharide (PAMPs) from a gran -ve bacteria interacts with activating receptors on B cells this will lead to intracellular detection of pathogenic patterns of DNA
29
diabetes mellitis patients versus normal
Type 1 diabetes B cells express class II and I MHC but they are only supposed to express class I leads to activation of autoreactive CD4+ T cells
30
explain innaproperiate expression of class II MHC
Expression of class II MHC on cells that do not normally express class II MHC can activate autoreactive CD4+ T cells
31
what causes the transfer of autoimmunity
tranfering CD4+ T cells and a lack of T reg cells
32
what increases autoimmunity
specific HLA alleles
33
what is necessary to have an autoimmune reaction
interaction bw TCR and self peptide AND MHC and self peptide
34
how do T regs supress autoreactive t h cells
they supress CD4+ t cells that interact with the same ppetide or different peptide if they are all intercating with the same APC lleads to linked supression
35
what is an example of an immunosupressant
cyclosporin A
36
what can be used as treatment for autoimmune diseases
immunosupressive therapy: immunosupressants general anti inflamamtory drugs depletion of CD4+ t cells using anti CD4 antibody other treatment: targetted therapies oral tolerance block only antigen activated T cells
37
does depletion of CD4 T cells using anti-CD4 antibody work
* Worked in mice * Not successful in humans; timing of treatment? *Humans diagnosed in later stages of disease compared to mouse models
38
what are some general targeted therapies for autoimmune treatment
anti cytokine antibodies or blockers Rituximab
39
what is rituximab
mAb against B cell CD20 - promotes B cell apoptosis and ADCC helpful for RA?
40
what are some anti cytokine antibodies and what do they do
block TNF-a embrel remicade humira
41
what are anti cytokine antibodies used for
crohns disease ankylosing spondyylitis
42
what is the advantage of blocking only ag activated T cells
overall immunity is not lowered
43
what is the challenge of blocking only ag activated T cells
target only activated T cells 1. we can use mAb against IL2-R, a subunit has promising resulst but BAD for T reg 2. block specific asssociated TCR chains
44
what type of autoiimune is SLE
type 3 formation of immune complexes that lead to compliment activation and deposition in kidneys- inflammation
45
how is SLE distributed in sex
10:1 females to males can be exacerbated during pregnancy there is a genetic predisposition and an HLA association
46
what is the symptom and underlying cause of SLE
unknown ag butterfly like rash and high levels of anti DNA abs
47
what is the visual symptom of hashimotos thyroiditis
goiter formation and hypothyroidism
48
what is the cuase of hashimotos thyroiditis
* Autoantibodies against microsomal & thyroglobulin * Sensitized T H1 cells for thyroid antigen * Intense infiltration of the thyroid gland by mononuclear cells * Interfere with iodine uptake & leads to decreased production of thyroid hormones
49
what mediates MS
T cells infiltrate the brain and cause inflammatory lesions inflammatory lesions destroy myelin shief of CNS autoreactive TH1 cells activate macrophages -leads to inflammation -inc macrophage, neutrophil, mast cells -Fas mediated death of oligodendeocytes
50
what causes MS
not known sequestered release of myelin Ags mollecular mimicry following viral infection (EBV)
51
what is the gentic component of MS
HLA class II DR15, DQ6
52
what cells are in type 1 IDDM
CD8+ TH1 Cytokines
53
what is the genetic component of type I diabetes
HLA Class II genes HLA DQ2. DQ8 and non HLA genes
54
what occurs in Type I diabetes
destrction of insulin producing B islet cells of pancreas leads to autonatibodies formation
55
what cells are involved in rheumatoid artheritis
autoreactive CD4+ TH1 cells CD4+ TH17 and cytokines lead to bone destruction macrophages and fibroblasts cause a feed forward inflammation
56
what cytokines in RA
IFNY and IL17
57
genetic component of RA
some HLA DR4 alleles
58
what are the immune complexes in RA
rheumatoid factor ++ IgM antibody against Fc region of igG molecules
59
what is RA
chronic inflammation and ersion of synoviun and bone
60

immunology (30 decks)

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