Review Type 1-4 Hypersensitivity Reactions

SLE
~ multiple genetic markers for lupus  different manifestations of the disease
~ often relapse symptoms
~ epidemiological trends – black America females of child bearing age
~ hormonally influenced? Not age related
~ improvement with pregnancy?
~ skin m/c affected, organs, blood cells, KI damage (often cause of death)
~ Antiphospholipid antibody
~ get hemorrhage and lack of clotting
~ in vitro – lack clotting, in vivo – tend towards thrombosis
~ potential cause of miscarriage (thrombosis in placenta)
~ “antiphospholipid antibody syndrome” – has had a thrombotic event AND presence of
Ab
~ can have this dx without lupus as primary diagnosis
~ correlated to endothelial damage (usually precedes development of thrombosis)
~ antinuclear Ab
~ run ANA titre  not very specific, can be to histones, chromatin, RNA, etc
~ sensitive but not specific, very little false positives
~ see certain patterns that are more specific to lupus – speckled pattern
~ 25% monozygotic twins have lupus together
~ might have something to do with complement deficiencies  Antigen sticks around
longer and may cause immune complexes to attack self along with Ag that are on
“Self cells”
~ overactive T and B cells  responds to something that it shouldn’t be responding to
~ increase number of B cells
~ increased responsiveness to cytokines that are secreted by T helper cells  causing
more B cell production  causing more Ab
~ skewed to CD4 T helper cell family (CD4 secrete cytokines when it sees Ag, and
cytokines activate all other aspects of immune system to facilitate process)
~ genetic susceptibility to lupus may have increase in 6 hydroxy-estrogen
~ take home message: there IS hormonal influence
~ infections agents always suspect in autoimmune diseases as a trigger
~ Type II and III involved in lupus
~ immune complex related in KI failure

~ autoAb destroy endothelial cells, get fibrosis, inflammatory leukocyte tries to patch up
blood vessel and then get lumen narrowing
~ causes acute necrotizing vasculitis
~ antiphospholipid Ab  increase hypercoagulability of blood, makes this situation
worse
~ skin conditions are worse with UV exposure
~ there are immune complexes at dermoepidermal junction
~ characteristic butterfly rash
~ often involve serosal layers
~ affect heart and lungs
~ pericarditis
~ valvular abnormalities, caused by fibrous tissue (that’s trying to repair damage to
endothelial layer)
~ see stenosis or regurgitation
~ Libman-Sacks – non bacterial verrucous endocarditis
~ more common before treatment with corticosteroids
~ coronary artery disease
~ thrombosis, damage to epithelium, often HTN (due to KI damage)
~ joints
~ mononuclear infiltration of synovial membrane
~ not really a big problem, it’s not erosive, just painful (arthralgia)
~ a bit of swelling
~ CNS
~ endothelial injury  intimal proliferation  microinfarcts  nerologic deficit
~ may have autoAb against synaptic structure
~ spleen
~ splenomegaly  fibrosis of arteries and capsule of SP  general decreased
function  enlarged
~ get immune system complex deposition in SP (should remove damaged immune
cells in body, cause SP to be overactive when there’s so many damaged immune cells)
~ serosal membranes
~ effusions  fibrinous exudates  opacification (white on CXR)
~ KI disease – m/c cause of death
~ KI trying to filter out immune complexes, but these get wedged in the small area in
the KI and then get inflammation  proliferation of endothelial cells  necrosis 
scarring  hematuria, proteinuria
~ most severe and common type  diffuse proliferative glomerulonephritis
~ severity really depends on genetic susceptibility
~ in diffuse proliferative GN and membranous GN can see nephrotic syndrome – not
filtering as much as you should  get more protein escaping  see edema, ascities

Rheumatoid Arthritis
~ no infectious process that’s making joints worse
~ still see systemic chronic inflammation – but NON supporative
~ there is extra articular involvement
~ may be infectious stimulant, maybe an organism causing the immune system to kick in
~ there isn’t an infection IN the joint, just that the immune system kicks in and makes
the rheumatoid arthritis worse
~ in Europe and Northern Africa have more
~ multiple genes involved
~ HLA DR4/DR1
~ may be specific to joint tissue
~ if there’s an Ag present, then activate T-helper cells, activate cytokines,
macrophages, B-cells in joint  inflammation, antibody production
~ type 4 hypersensitivity, not Ab mediated, it’s cell mediated
~ Rheumatoid factor (in 80% of those with RA)
~ IgMs against IgGs
~ immune complexes developed  see tissue damage  subQ nodules
~ extra articular manifestations are more Ab mediated
~ joint damage
~ CD4 activates plasma cells and cause macrophage infiltration
~ synovial cell proliferates and you get hyperplasia
~ neutrophil activation and fibrin deposition in joint space with proteolytic enzymes =
PANNUS
~ see proteolytic enzyme secretion  periarticular edema  activate osteoclast
around joint by cytokines in area  erosion of bone and cartilage  osteopenia, joint
fibrosis and calcification  ankylosis (linking of 2 bones and they fuse), bony
deformities
~ extra-articular manifestations
~ mediated by rheumatoid factor
~ subcutaneous nodules
~ fibrinoid necrosis surrounded by macrophages and granulation tissues
~ nodule tries to contain the immune complex
~ often forms in pressure points (ex: elbows), or viscera
~ also see vasculitis, serositis, uveitis, keratoconjunctivitis  all depends on genetic
susceptibility

Scleroderma
~ fibrosis of body tissues
~ middle aged women
~ diffuse – widespread skin involvement, rapid progression
~ limited – slow progression, minimal skin involvement
~ CREST syndrome – calcinosis, Raynaud phenomenom, esophageal immotility,
sclerodactly, telangectasia
~ Ag accumulate in area  endothelial injury  CD4 activation  cytokines get
secreted  activate B cells, mast cells, and macrophage  these secrete fibrogenic
cytokines (IL-1, TNF, etc)  get fibroblast activation  see excessive fibrotic tissue
~ see antinuclear Ab (ANA)  see anti-Scl 70 (common but not definitive? Acts as
markers)
~ 90% of patients have skin involvement
~ edema from infiltration of immune cells, see microvascular disease
~ there’s fibrosis of derma, atrophy of appendages, limited ROM, cutaneous
ulceration, tightening of skin, Raynaud’s
~ 90% have GIT problems
~ atrophy and fibrosis of muscularis  affects peristalsis and swallowing
~ strictures in esophagus, malabsorption (atrophy of the microvilli in small intestine)
~ LU (50%)
~ pulmonary fibrosis and endothelial damage
~ see pulmonary HTN  HT problems  R sided congestive HT failure  cor
pulmonale
~ KI (66%)
~ thickening of vessel walls of interlobular arteries (in lupus, the KI has immune
complex deposition which is type III)
~ HTN in KI  Renal stenosis  HTN in body
~ MSK
~ synovial hyperplasia and inflammation  fibrosis (no PANNUS formation as in
RA, no proteolytic enzymes that cause the destruction)

Sarcoidosis
~ see non-caseating granulomas
~ caseating granuloma is “cheesy”, so can’t ddx in CXR, need biopsy
~ will see granuloma in CXR in TB, CA, cystic fibrosis
~ t cell dysregulation
~ diagnosis of exclusion
~ see systemic systems  weakness, fatigue, spontaneous sweating, SOB, cough
~ little consistency in tests
~ see HLA association
~ progressive chronicity OR remission/relapse
~ possible microbial activation  see accumulation of CD4  which means less CD8
(cytotoxic)  increased TH1 (Ab production and inflammation) and other
inflammatory cytokines  macrophage activation  collection of epitheliod
histiocytes (mononuclear phagocytes) rimmed by CD4  epitheliod non-caseating
granuloma  proliferation of fibroblasts  scarification
~ mainly LU problem
Restrictive, pulmonary HTN
~ get bilateral hilar and peripheral lymphadenopathy (firm and hard – mimic CA)
~ in skin  erythema nodosum, granulomas, plaques
~ may affect eye, lacrimal gland, parotid gland, splenomegaly, hepatomegaly