immunopathology of inflammation and autoimmune disease Flashcards
what are the general principles of immune response?
degree of regulation
multilayer defense
network of pathogen recognition
effective intercellular communication
multiple mechanism of pathogen clearance
adaptive responses to changing pathogen
self regulation and limitation of host damage
what is autoimmunity?
it is a genetically determined, inherited immune system that is a theoretical concept - the skin acts as a barrier, and some people are more susceptible than others
what do pattern recognition receptors do in innate immunity?
they inform the immune system about the type of threat it is experiencing - i.e. gram negative, positive, viruses or fungi
which cells inform the adaptive immune system about the threat?
dendritic cells and macrophages
what are the characteristics of innate immunity?
it is pre-programmed, has no memory and is triggered quickly - within seconds - it provides the initial response to infection
what is involved in the adaptive immunity?
T cells, B cells and high affinity antibodies - more targeted and powerful immune responses, is highly tailored, has memory and takes 4-6 weeks
what is the function of cells of the innate immune system?
they recognise threat and engulf and destroy it
what are APCs?
antigen presenting cells - macrophages, monocytes and dendritic cells - they engulf debris, digest it and then present it as an antigen on their surface
what are phagocytes?
cells that engulf and destroy the cell and these are macrophages and monocytes
what are examples of granulocytes?
they have slightly different effector functions - eosinophils, neutrophils, mast cells and basophils
what are cytokines?
they are proteins of the innate immune system - they are chemical signals that modulate cell activity or attract cells
what are acute phase proteins?
they opsonise or present pathogens to the immune system - they coat pathogens to make them more visible e.g. CRP
what are complement proteins?
cascade of proteins with many functions such as opsonisation, killing, activation or chemoattraction
what is the Th1 response?
it is an adaptive response that means that cytotoxic T cells will directly kill the pathogen - this is if the pathogen has infiltrated the cell and there is less need for ABs
what is the Th2 response?
the adaptive response that produces lots of antibodies for opsonisation
what happens if there is no dangerous signal associated with tissue damage?
production of regulatory T cells
what do stem cells produce?
they produce phagocytes and APCs and lymphoid precursors which make NK, T, B and plasmacytoid dendritic cells
what is autoimmune disease?
breakdown of self tolerance and clinical entities - tendency of the immune system to be self reactive
what are the causes of AD?
there is a combination of factors - these are genetic (some people have different threshold for autoreactivity - some people may be genetically predisposed to have a more vigorous immune response), environmental - act on favourable genetic backgrounds and immune regulation
why are AD more common in women?
autoimmune disease is more common in women because there are immune genes on the X chromosome and depending on the number of chains this can lead to higher auto reactivity (more than 2)
why do T cells have some degree of autoreactivity?
to be selected for when developing T cells must engage their working receptors, and the only way to test this is through self antigens. therefore when they leave the thymus they will have some degree of autoreactivity. Those that show too much will be negatively selected (destroyed).
What is anergy?
occurs when there is engagement between a T cell and a APC when it is not presenting a harmful antigen - T cell becomes a peripheral regulatory T cell
what are other causative associations of AD?
sex - hormonal influence, age - elderly and environmental triggers - smoking, trauma tissue damage or infection
what does smoking and subsequent trauma result in?
the immune system becoming more pro-inflammatory due to damage to epithelial lining
what are HLA molecules?
they are proteins found on the surface of APCs that allow the immune system to recognise and react to pathogens - everyone has different HLAs
what does having the HLADRN51 phenotype result in?
allows you to present citrullinated proteins to immune system which are triggered by environmental factors - autoimmune response
what is the pathophysiology of AD?
autoreactive B cells and autoantibodies (directly cytotoxic and activation of complement - interfere with normal physiological function) and autoreactive T cells (directly cytotoxic and inflammatory cytokine production) - this results in general inflammation and end organ damage
what is characteristic of AD?
exacerbation and remission
what is organ specific AD?
it is affecting a single organ and is restricted to autoantigens of that organ only - it can overlap with other organ specific disease such as autoimmune thyroid disease
what is systemic AD?
affects multiple organs simultaneously, and is associated with autoantigens that are found on most cells of the body. It can overlap with other systemic AD particularly connective tissue disease
what are the two conditions in AI thyroid disease?
hashimotos thyroiditis and grave’s disease
what is hashimotos thyroiditis?
it is an AD that is to do with the destruction of thyroid follicles by autoimmune processes and is associated with autoantibodies of thyroglobulin and thyroid peroxidase - hypothyroidism
what is grave’s disease?
the inappropriate stimulation of the thyroid gland by anti-TSH autoantibody that leads to hyperthyroidism
what are scleroderma, polymositis, sjogrens syndrome and SLE examples of?
connective tissue disease
what are the two types of diagnostic tests and what do they test for?
non specific for inflammatory markers and disease specific such as autoantibody testing and HLA typing
what is ANA?
antinuclear antibody testing - investigation of systemic autoimmune disease
what is the treatment basis of AD?
supportive, immunosupressive and preventative
define immunosupression and what it can result in?
immunosupression is the artifical or natural process that turns off the immune response either partially or completely that can be accidentally or on purpose. This results in immunodeficiency which is the lack of an efficient immune system which results in susceptibility to infection
what are some uses of immunosupression?
transplant, autoimmune and lymphoproliferative
what is the difference between secondary and primary immunodeficiency?
immunodeficiency is usually secondary to external factors but it may be primary - genetic defects in the individual components of the immune system - type of infection is guide to underlying cause
what are the characteristics of secondary immunodeficiency?
transient or long lasting, minor or major trauma related cancer malnutrition radiation AD infection lymphocytes or neutrophils <1million/ml
what are the characteristics of primary immunodeficiency?
very rare
often diagnosed in early childhood but can present later in life
recurrent infection
what is SCID?
severe combined immunodeficiency syndromes - defects in B and T cells (more severe) - recurrent infections that are opportunistic - can used bone marrow transplantation can cure or gene therapy
