Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

SFM > immunological tolerance and autoimmunity > Flashcards

immunological tolerance and autoimmunity Flashcards

1
Q

immunulogical tolerance? what is challenge of it? mediated by?

A

unspecific unresponsiveness to ag

challenge is to understand how it becomes a pathological process , how T and B cells recognize self ags and contribute to tissue injury

mediated by IL-10

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

self-tolerance

A

all individuals are tolerant to specific self ag

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

autoimmunity

A

results from breakdown of self tolerance

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

negative selection

A

T lymphocytes should be doing this in the thymus, but it is not perfect

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

auto-reactivity

A

low level of it is crucial to normal immune function

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

central and peripheral tolerance

A

ag specific

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

central tolerance

A

induced in self reactive (immature) lymphocytes in primary lymphoid organs

ensures that lymphocytes are not reactive to self ags

results in:

  1. deletion by apoptosis
  2. change of BCR specifitiy
  3. development of Treg cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

peripheral T cell tolerance

A

induced in mature self-reactive lymphocytes in lymph nodes or peripheral sites such as submucosal tissues

needed to prevent activation of potentially dangerous lymphocyte clones in periphery

results in:

  1. inactivated (anergy)
  2. deleted (apoptosis)
  3. suppressed by Treg cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

central T cell tolerance- where does it take place and by what mechanisms

A

takes place in thymus**

T cells that have strong binding of self ags (negatively selected) are deleted by apoptosis

T cells that show no affinity or bind to self ag below threshold are positively selected migrate into blood as mature T cells

most will develop into effector CD4 and CD8 cells, small percent develop into Tregs

**further detail on question for AIRE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Treg cells? what do they do? what do they express? what is needed for their survival? what do they release to what?

A

natural Treg develop in thymus

respond to self ag but still positvely selected for

produce anti-apoptotic molecules which protect them from negative selection

also inhibit CD4 T cell activation and CD8 T cell differentation

prevent T cells from helping B cells in production of Abs

express FOXP3, CD4, CD25, CTLA-4

IL-2 critical for survival and function

long-lived

prevent autoimmune reactions in certain tissues- suppress activation of self reactive lymphocytes in peripheral tissues

release IL-4, IL-10, TGF-B to APC’s through cell to cell contact

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

Th0 cells- where are they produced?

what do they express?

what are they inhibited by?

A

induced Treg

outside of thymus- produced in GI and lymph nodes

FOXP3 exp induced in CD4 cells upon ag recognition and in presence of TGF-B if IL-16 is not present

if IL-6 is present- FOXP3 exp prevented and induced exp of RAR and RORyt leading to Th17 differentiation

development relationship between iTregs and Th17

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

anergy

A

functional unresponsive

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

suppression

A

block in activation by Treg

work through inhibitory receptors CTLA-4 and PD-1 (all CD4 and CD8 cells express these after ag stimulation)

cancer therapy- enhanced antitumor immune respone and tumor regression– checkpoint blockage

checkpoint blockade can form autoimmune reactions

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

deletion

A

apoptosis

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

anergy

A

functional unresponsive

is induced when there is no costimulation of CD80:CD28

anergic cells survive but are incapable of responding to ag

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

apoptosis

A

caused by cell receptor death or ag recognition without co stimulation

apoptotic inducers are released from mt

*two pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

mitochondrial (intrinsic pathway)

A

cell injury triggers BH3 proteins

BCL-2 upregulated (and effectors Bax, Bak)

cytochrome c and other pro-apoptotic proteins realeased

intiator: caspase 9
executioner: caspases

endonuclease activation and breakdown of cytoskeleton

sends DNA fragments out to surface of cell where ligands signal them for phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

death receptor (extrinsic pathway)

A

FasL binds to Fas on mt while TNF binds to TNF receptor

intiator: caspase 8
executioner: caspases

endonuclease activation

sends DNA fragments out to surface of cell where ligands signal them for phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

central B cell tolerance

A

immature B cells that recognize high avidity self ags in bone marrow will undergo receptor editing or apoptosis

low avidity for self ag will lead to anergic B cell

20
Q

receptor editing

A

rearrangment and replacement of Ig light chain gene that will continue to occur until the cell no longer recognizes self ag or cell dies

21
Q

BCR editing

A

all BCR’s that have light chain go through this

already express rearranged heavy chain

first recombines locus that encodes kappa light chain which yields a lymphocyte with autoreactive BCR– RAG1/RAG2 on during this

BCR continues recombination until it leads to IgL chain that lacks self reactivity– RAG1/RAG2 turned off

22
Q

RAG1/RAG2

A

control recombination

23
Q

peripheral B cell tolerance, problem that can occur

A

Mature B cells that recognize ag in the absence of Th cells may be rendered unresponsive or die by apoptosis

CD22 inhibitory signals is phosphorylated by Lyn which recruits SHP-1 tyrosine phosphatase which reduces BCR signaling

defects in Lyn, SHP-1, or CD22 lead to autoimmunity

24
Q

commensal microbes functions

A

reside in intestinal and respiratory tracts, on skin

  • inhibit pathogen coloinzation
  • supresses pathobionts through Tregs and IL-10
  • aid in deigestion and absorption of foods
  • have anti inflammaotry properties
  • important role in GALT development
25
GALT
upregulates Th17 and Th1 development upregulate barrier function
26
commensal microbe tolerance
exxagerated mucosal immunity to normal micrflora controlled by genetic factors cause of IBD
27
autoimmunity mechanism
mix of suspectibilty genes that fail to create self tolerance of B and T cells **and** tissue injury, activation of APC's activation of self reactive lymphocytes effector molecule cause tissue injusry and autoimmune disease
28
mutations that can break tolerance
AIRE C4 CTLA-4 Fas/FasL FoxP3 IL-2/IL-R2 SHP-1
29
AIRE functions
**autoimmune regulator** **tissue-restricted Ag's (TRA's) processed are expressed on surface of medullary thymic epithelial cell's HLA (regulated by AIRE) to bind to T cell to negatively select it**
30
AIRE def
AIREs are thought to be transcription factors that upregulate protein expression of self ag without it, decreased expression of self-Ags self-reactive T cells are not eliminated, enter tissues, cause injury
31
def in CP pathway of complement activation are linked to development of autoimmunity
.
32
C4 def
usually CR1 binds C3b's (which ag:ab complexes are bound to) from complement to RBC's (RBC:CR1) to have RBC' take to liver and spleen, phagocytically removing it from RBC's ## Footnote **when this can't happen, there is a defective clearnace of immune complexes**
33
regulation of T cell responses by inhibitory receptors
CD28-- terminates T cell responses CTLA-4
34
CTLA-4 role
homolog of CD28 inhibitory receptor terminate immune responses are maintain self tolerance
35
CTLA- def
enlarges lymphnodes to fatal level enhances autoimmune disease polymorphuism types-- type I diabetes and Grave's
36
two important properties of CTLA-4
low on resting T cells terminates continuing activation of T cells-- cell cycle arrest
37
two pathways of CTLA-4
cell-intrinsic: delivers inhibitory signals to T cells (feedback) cell-extrinsic: Treg's bind to B7 on on APC's which blocks their binding to CD28 on T cells
38
features of **chronic disease** autoimmunity
no fundamental difference between self and non self ags-- composed of same AA pathological immune response against self ag-- immune mediated inflammatory response activation of T and B cells is absense of infections **hypersensitve reactions**
39
how autoimmunity is prevented
1. immunological ignorance-- t cells separated from specific antigen 2. deletion-- Fas(CD95) receive signals from FasL-- apoptosis 3. inhibition-- CD80 binding B7 4. suppression-- Treg's release IL-10 and TGF-B
40
immune priviledged sites
eye brain pregnant uterus ovary testis adrenal cortex hair follicles if an allograft is placed in these sites, theyll survive if barrier is broken on these, autoimmune response
41
general features of autimmone disorders
sytemic or organ-specific various affector molecules to tissue injury chronic, progressive, self-perpetuating failure of B or T cell self tolerance complex polygenic traits multiple genetic polymorphisms increase disease suspetibility strongest association with MHC genes (most with class II) also non-HLA genes suspeptibility genes interact with environmental factors (tissue damage and infection)
42
role of environmental factors and ex
1. molecular mimicry ex: cross reactivity between strep and cardiac myosin 2. polyclonal activation: autoreactive lymphocrytes in cytokine field 3. microbes kill cells that cause release of previously sequestered ags from bursted cells
43
inflammatory bowel disease
**type IV hypersensitivity**-- bacteria from guts leaks into epithelial tissues, disrupts APC that is being bound to Th cell
44
systemic lupus erythematosus
type III hypersensitvity rashes, arthritis, glomerulonephritis, vasculitis triggered by auto-ab are found- most common anti-DNA abs anti-nuclear abs serve as diagnostic test
45
Rheumatoid arthritis
type IV hypersensitivity inflammation of synovium associated with destruction of bone and cartilage auto-ab is rheumatoid factor that reacts with circulating IgM and IgG that react with Fc portion of IgG rheumatoid factor- diagnostic marker other cells involved: Th1, Th17, B cells, macrophages, plasma cells
46
FoxP3 def
type of peripheral tolerance break symptoms: multi-organ lymphocytic infiltrates, wasting
47
Fas/FasL def

SFM (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions