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Exam 1 immuno > Tolerance and Autoimmunity > Flashcards

Tolerance and Autoimmunity Flashcards

1
Q

AutoImmunity results from the Breakdown of?

A

Self Tolerance

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2
Q

What induces Central tolerance and in what location?

A

Immature Self reactive Lymphocytes in Primary Lymphoid Organs

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3
Q

What induces Peripheral tolerance and in what location

A

Induced by mature self reactive lymphocytes in Lymph nodes or peripheral sites such as submucosal tissues

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4
Q

Three mechanisms to deal with recognition of self antigen in the central tolerance

A

Deletion by Apoptosis

Change of BCR specifitity

development of Treg cells

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5
Q

Three mechanisms induced in peripheral tolerance to deal with Mature self reactive lymphocytes

A

Inactivated (anergy)

Deleted ( apoptosis)

Suppressed by the Treg cells

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6
Q

Central T cell Tolerance location and Process

A

In Thymus

Strong binding to self Ags get deleted

No affinity at all undergo apoptosis

binding self antigen under certain threshold the develop into effector T cell

Small percentage develop into Treg Cells

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7
Q

Treg Cells

A

Develop in the Thymus

Positively selected due to strong TCR interactions with self AG

Not eliminated because can produce Anti Apoptotic molecules to protect them

Express FOXP3 and CD4+ and CD25+

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8
Q

Tregs need what to survive and function

A

IL-2

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9
Q

Induced Treg Cells

A

Produced outside of the Thymus and is induced by FOXP3 in Naive CD4+ upon AG recognition in the presence of TGF-B

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10
Q

Ag recognition in the presence of TGF-B and IL-6

A

Creation of Th17 cells rather than iTreg because IL-6 represses FoxP3 and induces expression of REtinoic acid receptor related orphan nuclear receptor (RORyt) to make Th17

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11
Q

Where are Inducible Treg cells produced

A

in the periphery especially in GI tract and Lymph nodes

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12
Q

What cytokines do Treg cells release

A

IL-4, IL-10, TGF-B

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13
Q

3 mechanisms of Peripheral tolerance?

A

Anergy- functional unresponsiveness

Suppression: Block activation of effector cell

Deletion: Promote APoptosis

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14
Q

what is the mechanism of T cell Anergy

A

Ag recognition with out adequate CD80:CD28 costimulation binding

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15
Q

What is the mechanism of T cell suppression

A

T rells may engage inhibitory receptors: CTLA-4 and PD-1

expressed on both CD4 and CD8

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16
Q

Therapeutic application of Anti-CTLA-4 and anti-PD1

A

Treat patients with cancer to enhance antitumor immune response leading to breakdown of tumor but does ldevelop auto immune reactions

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17
Q

What is the intrinsic pathway of apoptosis

A

Mitochondrial release of cytochrome C that activates caspase 9 that induces Death pathway

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18
Q

What is the Extrinsic pathway of Apoptosis

A

Death receptor FasL and Fas or TNF receptor that initiats Caspase 8 to induce apoptosis

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19
Q

3 outcomes of B cell Tolerance

A

die by apoptosis of high affinity for self

Receptor editing

Low avidity my lead to anergy in the bone marrow

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20
Q

BCR editing

A

the rearrangement occurs on the k light chain.

All BCR that contain the lambda light chain underwent BCR editing

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21
Q

Peripheral B cell Tolerance and mechanism of?

A

Mature B cell that recognize self Ag in peripheral tissues in the absence of specific Th cells may be rendered funcutionally unresponsive or die by apoptosis

CD22 inhibitory receptor is phosphorylation by Lyn and recruits SHP-1 tyrosine phosphatase to attenuate the BCR signaling

22
Q

What are some ways Treg cells mediate the peripheral tolerance

A

inhibit CD4 T cell activation by APCs

inhibit T cell differentiation into CD8 CTLs

Prevent T cells from providing help to B cells in producing Abs

23
Q

what is the function of Symbiotic bacteria

A

inhibit pathogen colonization of the GI tract and skin and have anti inflammatory activities

24
Q

How do Microflora suppress pathogens

A

induction of regulatory immune resposes involving Treg cells and IL-10

25
Q

What do Gut microbiota have an important role in the development of?

A

Gut associated Lymphoid tissue (GALT)

26
Q

How do You break Central Tolerance

A

Breakdown of AIRE

Autoimmune Polyendocrine syndrome (APS)

destruction of endocrine organs

27
Q

What Cells play an important role in negative selection of the Central Tolerance

A

Thymic Epithelial Cells function as APCs

28
Q

THymic Epthelial Cells

A

Have AIRE which is an important protein that helps express the peripheral tissues restrected Self (TRAs) that are presented to developing T cells

29
Q

What happens in the absence or mutation of AIRE

A

No expression of tissue restricted Ags (TRA) therefore no negative checking of immature T cells that lead to non elimination of self reactive T cells

30
Q

Breaking of Peripheral Tolerance: C4

A

SLE, cant clear the Immune complexes that leads to accumulation in blood and tissues

31
Q

Breaking of Peripheral Tolerance: CTLA-4

A

Failure of Anergy and suppression of CD4 T cells,

Polymorpismim diseases: Type 1 diabetes and Graves Disease

32
Q

Breaking of Peripheral Tolerance: Fas/FasL

A

Cant induce Apoptosis and lead to non dying self reactive B and T cells

ALPS

33
Q

Breaking of Peripheral Tolerance: FoxP3

A

Deficiency deficiency in T cells

34
Q

Breaking of Peripheral Tolerance: IL-2 or IL2Ra/b

A

Defective development and survival or function of regulatory T cells

35
Q

Breaking of Peripheral Tolerance:SHP-1

A

Failure of negative regulation of B cells

36
Q

Clearance of Immune Pathways

A

Need erythrocytes to bind to C3b (complement) on Immune complexes using its CR1 receptor

37
Q

Role of CTLA-4

A

is a homolog to CD28 and acts as an inhibitory receptor that binds CD80/B7) on B cells to terminate response

38
Q

Two important properties of the CTLA-4 receptor

A

low expression on resting T cells until cells are activated by Ag

Once expressed, CTLA-4 terminates continuing activation of these responding T cells

39
Q

Intrinsic function of CTLA-4

A

Engagement of CTLA-4 on a T cell that eliminates furthur activation

40
Q

Extrinsic function of CTLA-4

A

CTLA-4 on T regs bind B7 molecules on APC to block available B7 receptors for CD28

41
Q

How auto Immunity is prevented: immunological ignorance

A

Physical Separation

BBB
Eye
pregnant uterus
ovary
testis
Adrenal Cortex
Hair follicles
42
Q

How auto Immunity is prevented: Deletion

A

use FasL to promote Apoptosis

43
Q

How auto Immunity is prevented: Inhibition

A

Utilizing CTLA-4

44
Q

How auto Immunity is prevented: Suppresion

A

Use of Treg cells

45
Q

Various Types of Auto immune diseases and what genes are they predominantly found in

A

Class II HLA alleles (DR, DQ)

Ankylosing spondylitis
Rheumatoid Arthritis
Type 1 Diabetes
Pemphigus Vulgaris

46
Q

Microbial Ags can Initiate and Autoimmune disorder: Molecular mimicry

A

Cross reactivity effect cardiac myosin in rheumatic fever caused by streptococcal infection

Multiple sclerosis, T cells affect Mylein basic protein via Epstein Barr virus, influenza or human papillomavirus

47
Q

Microbial Ags can Initiate and Autoimmune disorder: Poly clonal bystander activation

A

Robust inflammatory response lead to activation of auto reactive lymphocytes in the cytokine field

48
Q

Microbial Ags can Initiate and Autoimmune disorder: Release of previously sequestered Ags

A

Microbes kill cells releasing sequestered Ags (DAMPS) that lead to immune response

49
Q

Inflammatory bowl syndrome

A

Changes in Gut microbiota lead to an inflammation response that can harm the Gut

50
Q

Systematic Lupus Erythematosus

A

Type 111 hypersensitivity

rash, arthritis, glomerulonephritis, and vasculitis due to Immune complex build up

Starts by defective clearance of apoptosis (UV damage)

51
Q

Rheumatoid ARTHIRITIS (RA)

A

inflammatory of the small and large joints

inflammation of the synovium with destruction of bone and cartilage

Type 4 hypersensitivity (Th17 play a role)

circulating IgG and IgM called rheumatoid factor

Exam 1 immuno (6 decks)

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