Introduction Flashcards
What is Autoimmunity?
Immune response against self-antigens
What is an immunogen
Substance elicits immune response
What is a Tolerogen
Antigens induce tolerance rather than immune response
What are the three ways that the body achieves self tolerance?
Segregate antigens (eyes)
Central tolerance - limits development of autoreactive B & T cells
Peripheral tolerance - regulates autoreactive cells in circulation
Why do we need central and peripheral tolerance of self- antigens?
Not all self antigens expressed in central lymphoid organs where negative selection occurs.
Explain what happens to immature T-lymphocytes when they bind differently to self-antigens during development in the thymus?
Binding: peptide bound to self MHC molecule:
Strong- -ve selection (apoptosis)
Intermediate - T reg. cell
weak - +ve selection
non - apoptosis
Explain what happens to immature B-lymphocytes when they bind differently to self-antigens during development in the Bone marrow?
High avidity - Leads to receptor editing, express new light chain and if still high avidity then apoptosis
Low avidity - Reduce receptor expression and become anergic ( wont respond to self antigen)
What happens during peripheral tolerance to T lymphocytes?
Normal response - (non self) T cell bins to Antigen Presenting Cell by a MHC + antigen complex ( co-stimulation) forming effector and memory T cells.
Self antigen response - T cell binds to Self antigen by MHC causing
anergy (functional unresponsiveness), suppression (block in activation by Treg cells)
or deletion (apoptosis)
what happens during peripheral tolerance to B lymphocytes?
Normal response (non self) binds and activates forming plasma cell and antibodies
Self antigen - BCR binds to self antigen and t cell isn’t active -> anergy, apoptosis or regulation by inhibitory receptors.
Central tolerance mechanism (short)
Deletion editing
Peripheral tolerance mechanism (short)
Cellular inactivation by weak signalling without co-stimulus
What is an Auto-Immune disease
High levels of auto-antibodies
Self tolerance fails
What genes are associated with autoimmunity?
MHC class 2 genes
What causes tissue injury in autoimmunity?
Activation of self-reactive lymphocytes
How do infections affect autoimmunity?
TRIGGERS autoimmunity usually:
Microbe causes activation of APC ( b7 and cd28 costimulatory molecules)
APC which has been activated has self-antigen on and T-cell becomes activated to target self antigen causing damage in self tissues.
May also have APC which is activated by a microbe where the antigen presented is a microbial antigen however looks like self.
Autoimmunity only when infection occurs- self tolerance without microbe as APC will be ‘resting’.
