Immunological Tolerance Flashcards

1
Q

Immunological tolerance?

A

Refers to mechanisms by which lack of immunological reactivity is induced and maintained

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2
Q

Self tolerance induction for B cells leads to?

A
  1. Deletion
  2. Paralysis of function
  3. Alteration of specificity
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3
Q

What percent of T cells die in thymus?

A

98

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4
Q

Children without thymus (Di George syndrome) do not…?

A

Have mature T cells

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5
Q

What happens in thymus involution?

A

Fat replaces thymocytes,

Degeneration complete at 30 years

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6
Q

Positive selection in thymus happens where?

A

In cortex

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7
Q

Negative selection happens where?

A

In medulla of thymus

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8
Q

What happens in negative selection?

A

Dendritic cells and macrophages at the cortico-medullary junction are APC expressing MHC 1 and 2 molecules and present self peptides to T cells

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9
Q

How does antigen in thymus mean the T cells wont react badly to other tissue antigen?

A

Thymus has autoimmune regulator AIRE. Transcription factor expressed at high levels by thymocytes medullary epithelial cells

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10
Q

Mutations of AIRE cause?

A

Autoimmune polyendocrinopathy with candidiasis and ectoderm all dysplasia (APECED)
Also called autoimmune poly endocrine syndrome

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11
Q

Split tolerance?

A

Auto reactive B cells can be present with being able to be activated as no T cell is reacting

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12
Q

Mechanisms of peripheral tolerance?

A

Ignorance: lymphocytes fail to recognise or respond

Clinal anergy: binding of antigen makes lymphocytes unresponsive

Suppression: interaction with suppressor cells/cytokines to inhibit lymphocyte responsiveness

Clonal exhaustion: continued stimulation by persistent antigen maya wear out responsive cells

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13
Q

Immunological privileges sites are what?

A

Sites in the body where T cells can’t reach antigen

E.g eye testis uterus placenta

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14
Q

Systemic ophthalmia?

A

Damage to one eye causes release of protein antigens. These are carried to lymph nodes and activate T cells. Effector T cells return and attack antigens in both eyes. Cause blindness in both damaged and undamaged eyes

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15
Q

How does induction of anergy occur?

A

Presentation without co-stimulation

CTLA-4 signalling

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16
Q

Checkpoint blockade is done through?

A

Anti CTLA 4 antibody, to allow the immune response to continue

17
Q

Blocking CTLA 4 promotes

A

Tumour rejection

18
Q

Absence of t reg cells is associated with?

A

Aggressive autoimmunity

19
Q

CD25 is?

A

Il-2Ra expressed by t reg cells

Consumes il2 to limit expansion of t eff

Depletion of cd25 and CD4 T cells lead to autoimmunity

20
Q

Foxp3

A

Forkhead winged helix transcriptor factor

Critical for t reg activity and development

21
Q

Mutations in foxp3 gene cause?

A

IPEX immunodysregulation, polyendocrinopathy and enteropathy x-linked syndrome- autoimmune disorder, systemic autoimmunity in first year of life

22
Q

Routes of administration?

A

Oral intratracheal orbital exposure can activate T cells to secrete TGFB (t regs)

23
Q

Where is tolerance to self antigens induced?

A

Central lymphoid organs

24
Q

What is immunosenescence?

A

Progressive deterioration of immune responses mainly associated with age

25
Immediate dosage favours?
Immunogenicity, whereas small or large favour tolerance
26
What is AIRE?
Transcription factor that is expressed at high levels by thymus medullary epithelial cells
27
What are the inhibitory receptors on exhausted T cells ?
CTLA4 PD1
28
Which antigen did they try for oral tolerance against rheumatoid arthritis?
Type 2 collagen