autoimmune diseases Flashcards
what is the difference between the innate and the adaptive immune system
innate - inflammation target tissues, macrophages, dendritic, mast, neutrophils, complement
no memory, amplification, fast response and short duration
adaptive - learned response - T/B cells
highly specific, strong memory and amplification - slow response
how do cells of the adaptive help the innate immune system and vice versa
innate APC’s present to T cells
T cell cytokines and B cell antibodies activate innate cells to cause inflammation
what are the 5 components of the innate immune system
phagocytic cells histamine producing cells complement cytokines chemokine
what are three types of phagocytic cells and what is their role
neutrophils - eat and destroy - pus
macrophages - produce chemokine
dendritic cells - present to T cells
what is the role of histamine producing cells and what are they
mast cells, basophils and eosinophils
produce histamines and other chemokines/cytokines
vasodilation and attract other immune cells
protect against parasites, wound healing, anaphylaxis and allergy
how does complement work in the innate immune system
directly attacks pathogen via alternative and lectin pathways
may be activated by adaptive immune system via antibodies
what is the role of cytokines and chemokine in the innate immune system
cytokines - signal between different cells (adaptive to innate etc)
chemokine attracts immune cells to sites of inflammation
what is autoimmunity defined as
the adaptive immune system recognises and targets the bodies own molecules cells and tissues
what are the main characteristics of autoimmunity
T cells that recognise self antigens
B cells and plasma cells that make autoantibodies
inflammation at targeted sites
what is the definition go autoinflmmation
not adaptive immune system - dysregulation of innate immune system
what are the main characteristics of auto inflammation and what are some examples
spontaneous systemic inflammation - no infection - no high tire autoantibodies or t cells ie no adaptive immune system
Traps - TNF receptor associated pyrexia - fever due to TNF releases
what are examples of auto inflammatory diseases compared to autoimmune
autoinflamamiton - hereditary periodic fevers, polygenic crohns
autoimmune - monogenic ALPS, SLE, polygenic RA
what is the conceptual basis of autoimmunity
breakdown of self-tolerance
what are the three causes of autoimmune disease
genes - won’t present till middle age
immune regulation
environment
describe central tolerance by the thymus
T cells in thymus develop receptors via random coding - some will be autoimmune
thymus then tests anybody to see if auotreactive then gets deleted (negative selection) - if doesn’t match normal antigen it gets rebased into circulation (positive circulation)
how are Treg cells made and what do they do
T cells with intermediate recognition with self-antigens
regulate suppression and expression of different T cells
what is the difference between MHC1 and MHC2
MHC1 - on all nucleated cells - presents antigen to CD8 cells which is cytotoxic
MHC2 only found in immune system eg APC takes antigen to lymph node
what do mutations in FOXP3 and PTPN22 cause
FOX - causes failure to develop regulatory T cells - severe autoimmunity from birth
PTP - T cells activated more easily - stronger immune response general
what are some causative associations with autoimmunity
sex ie more women than men
risk increases with age
sequestered antigens
environment triggers
what is molecular mimicry
in rheumatic fever - antigen on pathogen was similar to those on heart valves so they attack them as well as pathogen
describe three examples of how autoantgnes may cause autoimmunity
citrullination of proteins make them more immunogenic
tissue transglutamase alters gluten which binds to MHC - coeliac
failure to clear apoptotic debris (SLE) - more sequestered antigens in cells
what is the difference in role of TH1 vs TH2
TH1 - makes cytokine which stimulate macrophages to make more cytokines
TH2 - help B cells - to make antibodies
both lead to inflammation though
describe the pathophysiology of autoimmune disease
auto reactive b cells and autoantibodies - directly cytotoxic - activate compliment to own cell - general inflammation and end organ damage
what are the two types of autoimmune thyroid disease
hashimotos thyroiditis
graves disease
what is hashimotos thyroiditis
antibodies destroy thyroid - lead to hypothyroidism but destruction of thyroglobulin and thyroid peroxidase
what is graves disease
antibodies stimulate thyroid via anti-TSH autoantibody which resembles TSH - hyperthyroidism
what is myasthenia gravis
autoantibodies block Ach receptor - muscle weakness especially in the eyes
what is pernicious gravis
autoantibody binds to intrinsic factors and stops B12 binding and being absorbed
what is SLE
cell debris is not cleared quick enough - immune system recognises nuclear components as foreign
antibodies w antigens forms complex which actives complement and causes inflammation
give four examples of connective tissue autoimmune diseases
SLE, scleroderma, polymyositis, sjogrens
