Flashcards in immunopathology of inflammation and autoimmune disease Deck (43)
what are the general principles of immune response?
degree of regulation
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