Immunological Tolerance Flashcards
Immunological tolerance?
Refers to mechanisms by which lack of immunological reactivity is induced and maintained
Self tolerance induction for B cells leads to?
- Deletion
- Paralysis of function
- Alteration of specificity
What percent of T cells die in thymus?
98
Children without thymus (Di George syndrome) do not…?
Have mature T cells
What happens in thymus involution?
Fat replaces thymocytes,
Degeneration complete at 30 years
Positive selection in thymus happens where?
In cortex
Negative selection happens where?
In medulla of thymus
What happens in negative selection?
Dendritic cells and macrophages at the cortico-medullary junction are APC expressing MHC 1 and 2 molecules and present self peptides to T cells
How does antigen in thymus mean the T cells wont react badly to other tissue antigen?
Thymus has autoimmune regulator AIRE. Transcription factor expressed at high levels by thymocytes medullary epithelial cells
Mutations of AIRE cause?
Autoimmune polyendocrinopathy with candidiasis and ectoderm all dysplasia (APECED)
Also called autoimmune poly endocrine syndrome
Split tolerance?
Auto reactive B cells can be present with being able to be activated as no T cell is reacting
Mechanisms of peripheral tolerance?
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
Immunological privileges sites are what?
Sites in the body where T cells can’t reach antigen
E.g eye testis uterus placenta
Systemic ophthalmia?
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
How does induction of anergy occur?
Presentation without co-stimulation
CTLA-4 signalling
Checkpoint blockade is done through?
Anti CTLA 4 antibody, to allow the immune response to continue
Blocking CTLA 4 promotes
Tumour rejection
Absence of t reg cells is associated with?
Aggressive autoimmunity
CD25 is?
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
Foxp3
Forkhead winged helix transcriptor factor
Critical for t reg activity and development
Mutations in foxp3 gene cause?
IPEX immunodysregulation, polyendocrinopathy and enteropathy x-linked syndrome- autoimmune disorder, systemic autoimmunity in first year of life
Routes of administration?
Oral intratracheal orbital exposure can activate T cells to secrete TGFB (t regs)
Where is tolerance to self antigens induced?
Central lymphoid organs
What is immunosenescence?
Progressive deterioration of immune responses mainly associated with age
Immediate dosage favours?
Immunogenicity, whereas small or large favour tolerance
What is AIRE?
Transcription factor that is expressed at high levels by thymus medullary epithelial cells
What are the inhibitory receptors on exhausted T cells ?
CTLA4 PD1
Which antigen did they try for oral tolerance against rheumatoid arthritis?
Type 2 collagen
