Immunology of endocrine disease Flashcards
List some organ specific autoimmune disease
Type 1 DM
Hashimoto’s disease
Grave’s disease
List some non-organ specific autoimmune disease
Systelic lupus erythematous
Diffuse scleroderma
Polymyositis
Autoimmune disease occurs when what process breaks down
Self tolerance - immune system is usually specifically unreactive (tolerant) to self antigens
Properties of non-organ specific autoimmune diseases (3)
Affect multiple organs
Associated with autoimmune responses against self-antigens distributed all throughout body
Often attack intracellular molecules involved in transcription and translation
Properties of organ specific autoimmune disease (2)
Restricted to one organ
Typically affects endocrine glands
What self antigen is attacked in Addison’s disease
21-hydroxylase
Almost all types of autoimmune diseases are more common in women, except what
Ankylosing spondylitis
Define tolerogens
Antigens that induce tolerance of the immune system
Define self tolerance
Tolerance to self antigens; fundamental property of immune system to be unresponsive to a harmless antigen
Multifactorial aetiology of autoimmune disease
- genetic (1)
- environmental (4)
Genetic factors
-mutation of HLA gene
Environmental factors
- hormones
- infection
- iatrogenic (drugs)
- UV radiation
What is the human leukocyte antigen (HLA) complex
a set of cell surface proteins essential for the acquired immune system to recognise foreign molecules from self antigens coded for by the human leukocyte antigen (consists of a family of genes that code for the HLA complex)
is the human version of the major histocompatibility complex (MHC)
To avoid autoimmune disease, T and B cells that have high affinity to self antigens are eliminated or suppressed by what mechanisms
Central tolerance
Peripheral tolerance
Central tolerance occurs where (2)
Peripheral tolerance occurs where (2)
Generative (PRIMARY) lymphoid organs
- Thymus
- Bone marrow
Secondary lymphoid organs
- spleen
- lymph nodes
What is peripheral tolerance
Secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs (thymus and bone marrow)
What is central tolerance
also known as negative selection, is the process of eliminating any developing T or B lymphocytes that have receptors specifically reactive to self antigens at an early stage
Mechanisms of central tolerance
B cell tolerance (in bone marrow)
-those with high affinity to self antigens undergo negative selection and are eliminated via apoptosis
T cell tolerance (in thymus)
- T cells undergo positive and negative selection
- those that have low affinity to self antigens go on to differentiate into single positive CD4 or CD8 T lymphocytes
- some CD4+ T cells with moderate affinity for self antigens receive a survival signal (+ve selection) and differentiate into T regulatory cells
Mechanisms of peripheral tolerance (3)
Anergy (a state of inactivation in which the lymphocytes remain alive but are unable to respond to antigen)
Treg suppression - block activation of lymphocytes
Apoptosis - induce death of these lymphocytes
Name some antigen presenting cells
Dendritic cells
Macrophages
Treg cells develop from what
CD4+ T cells
Overcoming peripheral tolerance is a contributing factor to the process of autoimmunity; in what ways is peripheral tolerance overcome (3)
Inappropriate access of self-antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in the ways in which self-molecules are presented to the immune system
Breakdown of peripheral tolerance is more likely to happen when what is present
Inflammation/tissue injury due to increased activity of proteolytic enzymes –> increased protein breakdown –> high concentrations of peptides being presented to responsive to T cells
How may self antigens bypass previously established tolerance
May be altered by viruses, free radials or radiation
Apart of overcoming peripheral tolerance, there’s another immunopathological mechanism that can contribute to autoimmune disease which involves structural similarity between self antigens and antigens of microbes - what is this called
Molecular mimicry
What is epitope spreading
Once peripheral tolerance has broken down, continuous inflammation can allow presentation of further peptides and local tissue damage accelerates so immune response broadens