Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PM3 - Infection and immunity > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

autoimmune diseases are …

A

… chronic, progressive and self-perpetuating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

sterile inflammation

A

TISSUE INJURY: inflammation -> repair -> fibrosis, metaplasia and or tumor

TISSUE STRESS/MALFUNCTION: inflammation -> adaptation to stress -> homeostasis -> shift leads to new homeostasis, disease or autoinflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

autoinflammatory disorders
definition, example

A

inherited
involve “unprovoked” innate-mediated inflammation
rhythmic, recurrend

e.g. familial fever syndromes -> FMF -> mutated FMF gene encoding for PYR -> excessive inflammasome activation if homozygous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

therapy of autoinflammatory disorders

A

recombinant IL6R Ab
neutralizing IL1b Ab
IL1R atagonist
decoy IL1R
anti-TNF blockers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

causes for autoimmunity (general)

A

genetics + infection + environment lead to breakdown of tolerance

abnormal display of self-Ag, inflammation, initial innnate response, genetically linked to MHC (HLA complex) abnormalities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

infections triggring autoimmunity
mechanisms

A

BYSTANDER ACTIVATION: activated T cells are not specific!

MOLECUAR MIMICRY: Ag similar to endogenous protein (e.g. EBV and myelin in MS), cross-reactivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

systemic vs organ-specific manifestation of autoimmunity

A

SYSTEMIC: by self-nucleolar Ab or specific Ab (circulating!)

ORGAN-SPECIFIC: Ab or response against tissue-restricted features

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

environmental trigger tissue injury
autoimmunity

A

tissue injury can lead to exposure of previously concealed Ag
autoimmunity induced by immune complexes, circulating auto-AB or autoreactive T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

causes for tolerance failure

A
  • defects in negative selection of T and B cells
  • defects in receptor editin (B cells)
  • defects in inhibitory pathways and receptors
  • reduced number or function of Tregs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

TGFb

A

driver of Treg and TH17 (in combination with IL6) differentiation
inhibits TH1 and TH2

produced by DC, Treg, MDSC, TAM2 and tumor cells
activates RORgt (TH17)

immunosuppressive towards CD4, CD8, NK cells
beneficial for Treg and TAM (and TH17)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

IL6

A

proinflammatory cytokine
produced by many cells and initiated by many cytokines

with TGFb -> activation of STAT3 -> TH17
loss of IL6 -> Treg increases

promotes T cell survival, proliferation, recruitment and subset committment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

IL23

A

promotes TH17 poarization
IL23R initially not expressed on naive T cells -> not involved in initiation
important for full, sustained and stable differentiation

induces IL17 and IL6, IL1 and TNF -> inflammation (GIT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Treg in autoimmunity

A

balance the immune response
establish peripheral tolerance
prevent autoimmunity
autoimmunity developes when numbers or function is reduced, or T cells become resistant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

DC in autoimmunity

A

establishing central tolerance -> mTEC (TRA) and AIRE-mediated
maintaining peripheral tolerance by self-Ag presentation and induction of irrreversible unresponsiveness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

B cells in autoimmunity

A

formation of immune complexes (Ab) -> can engage B cells, FcR bearing cells, and complement system -> inflammation
can display Ag and co-stimulators -> T cell activation
cytokine release
organized lymphoid structure organisation (via lymphotoxin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

single-gene abnormalities causing autoimmunity

A

influence tolerance
- central tolerance (AIRE)
- generating T reg (FoxP3, IL2, IL2R)
- anergy and function of Treg (CTLA4)
- peripheral T and B differentiation

17
Q

factors involved in autoimmunity

A

genetic
infections
tissue alterations
hormones
microbiota

18
Q

Ab as autoimmunity-causing factor

A
  • TISSUE DISRUPTION: via opsonization and phagocytosis -> Ab bind cells -> immmune recruitment and tissue injury
  • IMMUNE COMPLEXES: deposition in vessel walls -> vascular inflammation, ischemic damage, e.g. serum sickness
  • RECEPTOR INTERACTIONS: blocking receptor-ligand interaction or activating receptor
19
Q

GBS
target, effect, pot. cause

A

Guillain-Barré-Syndrome

TARGET: PNS via Ab (depending on Ab different symptoms)
EFFECT: rapid progressive weakness, maybe respiatory muscles affected
POST-INFECTION: can develop 1-3 weeks after infections, esp. GBS I since not predominant in women, no HLA association and monophasic disease course

20
Q

SLE
target, cause, pathogenesis

A

systemic Lupus erthematodes

chronic, remitting and relapsing

TARGET: many different autoAb, most frequent are anti-nuclear Ab

CAUSE: auto-Ab form immune complexes -> inflammatory disease
- GENETIC: insufficient clearance of apoptotic fragements (C1q deficiency)
- ENVIRONMENTAL: extensive cell death or injury -> increased DNA exposure

PATHOGENESIS: clearance hypothesis
- inadequate clearance leads to increased nuclear Ag burden
- immune complex formation
- FcgRIII on pDC binds immune complexes
- TLR7/9 signalling -> DC maturation
- stimulation of self reactive B cells -> Ab increases

TLR7 escape during X inactivation -> extensive TLR 7 signalling in 35% of women

21
Q

SLE
clinic, therapy

A

M:F = 1:10
can cause glomerulonephritis, anemia, thrombocytopenia, CNS manifestations

small arteries freuently affected
systemic, psychological manifestations, afferences (figers, toes, nose) affected

THERAPY: no cure or prevention, clinical trials for
- anti-IFNg Ab
- TLR inhibition
- anti-CD20 or anti-BAFF mediated B cell depletion

22
Q

clearance hypothesis

A

pathogenesis of SLE

PATHOGENESIS: clearance hypothesis
- inadequate clearance leads to increased nuclear Ag burden
- immune complex formation
- FcgRIII on pDC binds immune complexes
- TLR7/9 signalling -> DC maturation
- stimulation of self reactive B cells -> Ab increases

TLR7 escape during X inactivation -> extensive TLR 7 signalling in 35% of women

23
Q

Cause of SLE

A

CAUSE: auto-Ab form immune complexes -> inflammatory disease
- GENETIC: insufficient clearance of apoptotic fragements (C1q deficiency)
- ENVIRONMENTAL: extensive cell death or injury -> increased DNA exposure

24
Q

Pathogenesis SLE

A

PATHOGENESIS: clearance hypothesis
- inadequate clearance leads to increased nuclear Ag burden
- immune complex formation
- FcgRIII on pDC binds immune complexes
- TLR7/9 signalling -> DC maturation
- stimulation of self reactive B cells -> Ab increases

TLR7 escape during X inactivation -> extensive TLR 7 signalling in 35% of women

25
Q

Therapy SLE

A

THERAPY: no cure or prevention, clinical trials for
- anti-IFNg Ab
- TLR inhibition
- anti-CD20 or anti-BAFF mediated B cell depletion

26
Q

RA
target, cells & cytokines, therapy

A

rheumatoid arthritis

TARGET: synovium -> inflammation , destruction of cartilage and bone

CELLS and CYTOKINES: many involved
-> TH17, TH1, cells, macrophages, tertiary lymphoid structures
-> IL1, IL6, TNF & IL8, IL17, IFNg

THERAPY: TNF antagonists, anti-IL6 Ab, IL1 antagonists, JAK inhibition, anti-CD20, B7:CD28 interaction blockage

27
Q

RA
therapy

A

THERAPY:
- TNF antagonists
- anti-IL6 Ab
- IL1 antagonists
- JAK inhibition
- anti-CD20, B7:CD28 interaction blockage

28
Q

MS
target, onset therapy

A

multiple sclerosis

TARGET: myelin (CNS)

ONSET: genetically predisposed exposed to unknown trigger (ev. EBV infection -> molecular mimicry)

THERAPY:
- HALT MS: prevention of relapsng remitting MS -> chemo and autologous HSC Tx -> CD4 reduced, Tregs increased, but re-emergence of myelin-specific cells
- FINGOLIMOD: reduces SIP1 receptors (mediate T-CM circulation), retention in LN and no CNS invasion
- mRNA VACCINE: non-immunogenic vaccine Ag delivered to DC, expansion of Ag-specific effector Treg

29
Q

MS
target, onset therapy

A

multiple sclerosis

TARGET: myelin (CNS)

ONSET: genetically predisposed exposed to unknown trigger (ev. EBV infection -> molecular mimicry)

THERAPY:
- HALT MS: prevention of relapsng remitting MS -> chemo and autologous HSC Tx -> CD4 reduced, Tregs increased, but re-emergence of myelin-specific cells
- FINGOLIMOD: reduces SIP1 receptors (mediate T-CM circulation), retention in LN and no CNS invasion
- mRNA VACCINE: non-immunogenic vaccine Ag delivered to DC, expansion of Ag-specific effector Treg

30
Q

MS therapy

A
  • HALT MS: prevention of relapsng remitting MS -> chemo and autologous HSC Tx -> CD4 reduced, Tregs increased, but re-emergence of myelin-specific cells
  • FINGOLIMOD: reduces SIP1 receptors (mediate T-CM circulation), retention in LN and no CNS invasion
  • mRNA VACCINE: non-immunogenic vaccine Ag delivered to DC, expansion of Ag-specific effector Treg
31
Q

DM1
target, disease complictions and pathogenesis

A

Diabetes mellitus Type I

TARGET: pancreal beta-clells producing Insulin

Complications: CV diseasem renal failure, severe sight impairment

PATHOGENESIS: inflammation in islet cells leads to necrosis and lymphocyte infiltration
- TH1 reactive towards islet Ag
- CTL mediated lysis
- autoAb
- damaging local TNF and IL1

32
Q

DM1
genetics

A

strong HLA association
HLA-DQ 2&8, HLA-DR3&4 have increased susceptibility
HLA-DQ6, HLA-DR2 is potective

polymorphisms in IL2 & CD25, IDD12 (CTLA4) or IDD2 (insulin)
reduced Vitamin D exposure

33
Q

DM1
therapy

A

try to induce tolerance with diabetogenic peptides from islet Ag
generating/giving Tregs

TEPELIZUMAB: anti-CD3 mAb, improves/stabalizes beta cell function in Ab+ high risk patinets

34
Q

tepelizumab

A

treatment of DM1

anti-CD3 mAb, improves/stabalizes beta cell function in Ab+ high risk patinets

35
Q

Inflammatory bowel disease
definition, cause, clinic, therapy

A

heterogenous group of chronic remitting inflammations
-> e.g. Chron’s, ulcerative colitis

CAUSE: most likely poorly regulated response to commensal bacteria

CLINIC: abdominal pain, vomitiing, diarrhea, weight loss

THERAPY: anti-inflammatory drugs

36
Q

APS-I
cause, symptoms

A

autoimmune polyendocrine syndrome type 1
AIRE-deficiency

AIRE: mediates TRA presentation by mTECs -> no negative selection

SYMPTOMS: chronic candidiasis, hypoparathyreoidism, adrenocortical failure

37
Q

Therapeutic approaches for autoimmune diseases

A
  • anti-inflammatory agents
  • depletion of cells or Ab
  • anti-cytokine drugs/Ab
  • interrupting cell interaction/migration (B7 block, intergin Ab)
  • Tolerisation (Ag-specific, blunt autoimmunity and no impairment of IS)
    -Treg transfer

PM3 - Infection and immunity (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions