Autoimmune disorders and review of immuno Flashcards
Things to protect the GI epithelium?
single epithelium mucus antimictobial made peptides commensal bacteria (competes) Peyer's patches
Shigella infection?
Gram neg rods, non motile and passed person to person by fecal-oral route
they survive in the stomach acids, reach and penetrate the mucus via M calls, then invade and destroy adjacent epithelial cells
Dendritic cells take up antigen travel to follicles and lymph nodes to activate T cells and B cells are also stimulated and antibody produced
Antibody production does what?
prevents further bacteria invasion and CD8+ T cells kill infeced cells
Mechanisms that help prevent lymphocyte mediated autoimmune disease?
central intolerance (clonal deletion) peripheral intolerance (anergy, deletion, suppression)
T cell activation?
the initiating agent or primary self antigen is unknown for many of these disease
genetics often contribute to the development of disease or susceptibilty, and for many of them HLA genes play a role
Immunologic mechanisms of joint disease?
T cell activation
Excess Immune complex formation
HLA genes play a role in many of them
autoimmune in this study?
sytemic lupus erthematosus
rehumatoid arthritis
juvenile idiopathic arthritis
reactive arthritis
lab results lupus?
low hemoglobin low WBC count high CRP high ESR (sed rate) negative for RF low level complement positive for autoantibodeis andi-ds DNA, DAT (antobodies for erthyroctyres)
SLE?
is a complex autoimmune disease involving chronic systemic inflammation
multiple organ systems are usually involved
Major immuno features with SLE?
anti-nuclear antibody (ANA)
antibody against ds DNA
immune complex depositis in skin and kidneys
other autoantibody
major clin manifest systemic lupus erythematous?
hematologic (always) arthritis skin fever renal
rash with SLE?
butterfly rash
Make the self antigens?
genetic susceptible indicidual– undergoes an environmental trigger, cause t cell driving force, IgG autoantibody production (also from other cellular immune defects)– autoantibody mediated clinical manifest
main genes for genetic susceptible?
MHC class I, complement
Antinuclear antibody most common in SLE?
against double stranded DNA and the nuclear Smith antigen are most specific for SLE
(histones second)
Diagnose SLE?
antinuclear antibody patterns on immunofluorescence
add patient serum to fix
predomiance of antigen bound but antibody makes the pattern
antiphospholipid antibodies (aPLA)
some SLE patients develop these, can affect coagulation and endothelium
promotes thrombus formation, platelet aggregation, and are asssociated with fetal loss
(antiphospholipid syndrome)
Rheumatoid arthritis?
chronic, inflammatory disease of the joints with varying degrees of systemic involvement
major immuno features of RA?
RF, anti-citrullinated protein antibody (ACPA), and immune complexes
inflammtory infiltrate into the joints
HLA associations
small joints (hands, wrists, ankles)
Rheumatoid nodules?
raised firm extensor surfaces, derived from necrotic blood vessels
Diagnose RA?
morning stiff, 3 or more joints, hand joints, symmetric, nodules, serum RF (ACPA more specific) radiologic changes
key factors to RA?
genetic factors and environmental triggers
citrullination of proteins and immune response to them (ACPA)
inflammtory reactions occur within the joints fueled by adaptive immune responses
production of other autoantibodies
HLA associated with RA?
HLA-DRB1
cytokines involved with RA?
IL-1, IL-6, TNF
IL-6?
activates luekocytes, B cell differentiation, active phase response
TNFalpha?
induce production of proinflammatory cytokines
stimulates and activates endothelial cells, lead to further recruit of cells within the joint
stimulates cells within joint to break down the matrix wihich surrounds them
stimulates macrophages to produce matric metallo-proteinases and free radicals
IL-1?
activates leukocytes, endothelial cells, fibroblasts, osteoclasts
IL-17?
helps activate fibroblasts, chrondrocytes, recruit neutrophils
early changes in RA?
inflammatory cells in the joint, neutrophils (fluid), lymph (membrane)
middle stages of RA joint destruction?
synovium thickens
prolferative fibroblast
erosion of bone
Late stages of RA joint destruction?
hyperplastic expanding vascular pannus
Vascular pannus?
fibroblast like synovial cells, lymphocytes, macrophages, and other cell types releasing a number of proinflammatory cytokines and destructive enzymes
bone resorption?
neurovascularization and an environment which promotes growth and activity of osteoclasts
Systemic conseuqneces of RA?
shortedend life span increase risk of CV disease fatigue reduced cognitive function, osteoporosis increased risk of lymphoma increased risk of inflammatory and fibrotic lung disease
Junvenile Idiopathic Arthritis? (JIA)
hetergenous group of autoimmune diseases of unknown etiology, under 16 yo, chronic arthritis, often larger joints (knee)
characteristics of JIA?
HLA associations
ANA+ in 40 % of patients
+- for RF
activated CD4+ T cells and inflammtory cytokines
Histo JIA?
thickened hyperplastic
synovium that is highly vascular and contains a dense infiltrate of inflammatory cells- T cells, macrophages, and DCs
criteria for JIA?
age of onset <16 yo
arthritis in 1 or more joints, swelling or effusion, (limit motion, tenderness or pain on motion, heat)
symptoms present for 6 wks or longer
type of onset classified one of many
exclusion of other forms of junvile arthitis
involve hip
can resemble RA (poly)
classify JIA?
oligoarticular, polyarticular, systemic (Stills disease), psoriatic junveille idopathic arthritis, enthesitis related arthritis
Reactive arthritis?
seronegative spondlyoarthropathy (neg for RA)
triggered by enteric or urogential infections (Chlamydia tachomatis, Salmonella, Shigella, Yersinia)
peak onset 15-35
HLA-B27
not autoimmune related, molecular mimicry
Systemic (still’s disease)?
fever spikes predictable pink rash, abdomen, extremities, hepatosplenomegaly, lympadenopathy
HLA associations?
SLE- anti-nuclear antibody aganist ds DNA
RA- HLA-DRB1
JIA- HLA assocations
Reative arthritis- HLA-B27
Reiter’s syndrome?
triad, one presentation of reactive arthritis
Ankylosing Sondylitis?
chronic inflammatory disease of sacroiliac joint, vertebrae, entheses
Low back pain +- anterior uveitis (inflamme uvea)
lesions are painful and tender to the touch
Common sites of ankylosing sponylitis?
insetion of achilles tendon and of the plantar fascia on the calcaneus
characteristics of ankylosing sponylitis?
HLA-B27+, RF neg
xray findings and positive Schober’s test
