CP8 - Autoimmune Diseases Flashcards
what are the characteristics of autoimmunity?
- theoretical concept
- inherited
- genetically determined
what are the characteristics of autoimmune disease?
- distinct clinical entity
- due to a breakdown of self-tolerance
- caused by environmental factors acting on a favourable genetic background
what are the 3 contributing factors of autoimmune disease?
- genes
- immune regulation
- environment
what is central tolerance?
carried out in the bone marrow for b cella and thymus for t cells. it involves conditioning the b and t cells not to attack self antigens
what is positive selection?
cells are let free if they don’t attack self antigens
what is negative selection?
cells are destroyed if they attack self antigens
what is peripheral tolerance?
if some t cells enter the circulation and attack self antigens, lymph nodes will destroy them (similar system for b cells)
which genes are thought to have a role in shaping the behaviour of T cells?
class II MHC
what is the effect of a mutation in FoxP3?
failure in development of Treg cells, severe autoimmunity from birth
what is the effect of mutation in PTPN22?
easier activation of T cells, leading to a much stronger response than expected.
what are the risk factors for autoimmunity?
- genetics
- sex (due to hormonal influence, women more prone)
- age - elderly more prone
- concealed antigens in the body may be recognised as foreign by the immune system, e.g., nucleus, eye, testis
- environmental triggers
- changing the amount or nature of self antigens
which environmental triggers could act as risk factors for autoimmunity?
- infection - activates immune system but could cause autoimmunity if it goes too far
- trauma
- smoking
what is citrullation?
conversion of the amino acid arginine in a protein to the amino acid citrulline. one of the causes of RA
what is the disease mechanism which causes SLE?
failure to clear apoptotic debris, increasing the availability of sequestered antigens inside the cells
how do t cells cause inflammation?
- releasing inflammatory cytokines
2. helping b cells make antibodies
why does inflammation not result immediately?
there is a time delay between when the immune system makes a mistake and when inflammation results
what are the 2 types of pathophysiology of autoimmunity?
- autoreactive b cells and autoantibodies
- auto reactive t cells
leads to general inflammation and end-organ damage
what is the pathophysiology of auto reactive b cells and autoantibodies?
they are directly cytotoxic
activate complement and interfere with normal physiological function
what is the pathophysiology of auto reactive t cells?
directly cytotoxic
produce inflammatory cytokines
activate b cells
what are the general clinical features of autoimmune disease?
- more than 100 different diseases
- can affect any organ
- onset - usually middle or old age
- leads to a loss of organ function
- chronic condition - life long
- some have a characteristic exacerbation and remission (eg. MS)
- it is common for diseases to overlap
what are the characteristics of organ specific autoimmune disease?
- affect only one organ
- autoimmunity restricted to auto antigens of that organ
- overlap with other organ specific diseases
- eg. autoimmune thyroid disease
what are the characteristics of systemic autoimmune diseases?
- can affect several organs
- autoimmunity associated with auto antigens found in most cells of the body
- overlap with other non-organ specific diseases
- eg. connective tissue diseases (another name for non-organ specific, nothing to do with connective tissues)
name some examples of organ specific autoimmune diseases
- hashimoto’s thyroiditis
- grave’s disease
- myasthenia gravis
- pernicious anaemia
name some examples of systemic autoimmune diseases
- SLE
what are the characteristics of hashimoto’s thyroiditis?
destruction of thyroid follicles, by auto antigens thyroglobulin and thyroid peroxidase
leads to hypothyroidism
what are the characteristics of graves disease?
inappropriate stimulation of thyroid gland by autoantibody for anti-TSH antibody
imitates TSH, binds to its receptor and stimulates it
what are the characteristics of myasthenia gravis?
in the NMJ, antibodies bind to the ACh receptor and block it. therefore, the muscle is unable to function. usually accompanied by a tumour in the thymus.
worsens as the day progresses
what causes pernicious anaemia?
failure of via b12 absorption in the gut. antibodies bind to IF, which is required for b12 absorption.
what happens in SLE?
antibodies are formed against the antigens in the nucleus. bind to them and form immune complexes in the circulation. these complexes deposit in any organ, activate the complement and cause inflammation
what are the main distinguishing characteristics of auto inflammation from autoimmune diseases?
- seemingly spontaneous attacks of systemic inflammation
- no demonstrate source of infection identified as a cause
- absence of high titre autoantibodies and antigen specific auto reactive t cells
- no evidence of auto antigenic exposure
