Immunological Tolerance

Question 1

Immunological tolerance?

Answer 1

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

Question 2

Self tolerance induction for B cells leads to?

Answer 2

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

Question 3

What percent of T cells die in thymus?

Answer 3

98

Question 4

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

Answer 4

Have mature T cells

Question 5

What happens in thymus involution?

Answer 5

Fat replaces thymocytes,

Degeneration complete at 30 years

Question 6

Positive selection in thymus happens where?

Answer 6

In cortex

Question 7

Negative selection happens where?

Answer 7

In medulla of thymus

Question 8

What happens in negative selection?

Answer 8

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

Question 9

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

Answer 9

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

Question 10

Mutations of AIRE cause?

Answer 10

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

Question 11

Split tolerance?

Answer 11

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

Question 12

Mechanisms of peripheral tolerance?

Answer 12

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

Question 13

Immunological privileges sites are what?

Answer 13

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

E.g eye testis uterus placenta

Question 14

Systemic ophthalmia?

Answer 14

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

Question 15

How does induction of anergy occur?

Answer 15

Presentation without co-stimulation

CTLA-4 signalling

Question 16

Checkpoint blockade is done through?

Answer 16

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

Question 17

Blocking CTLA 4 promotes

Answer 17

Tumour rejection

Question 18

Absence of t reg cells is associated with?

Answer 18

Aggressive autoimmunity

Question 19

CD25 is?

Answer 19

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

Question 20

Foxp3

Answer 20

Forkhead winged helix transcriptor factor

Critical for t reg activity and development

Question 21

Mutations in foxp3 gene cause?

Answer 21

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

Question 22

Routes of administration?

Answer 22

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

Question 23

Where is tolerance to self antigens induced?

Answer 23

Central lymphoid organs

Question 24

What is immunosenescence?

Answer 24

Progressive deterioration of immune responses mainly associated with age

Question 25

Immediate dosage favours?

Answer 25

Immunogenicity, whereas small or large favour tolerance

Question 26

What is AIRE?

Answer 26

Transcription factor that is expressed at high levels by thymus medullary epithelial cells

Question 27

What are the inhibitory receptors on exhausted T cells ?

Answer 27

CTLA4 PD1

Question 28

Which antigen did they try for oral tolerance against rheumatoid arthritis?

Answer 28

Type 2 collagen