immunology set 2.3 - autoimmune diseases

MS is the most common disease of

CNS myelin

multiple sclerosis

myelin sheath destruction. disruptions in nerve impulse conduction

systemic lupus erythematosus (SLE)

chronic autoimmune inflammatory disease of collagen in skin, joints, and internal organs

SLE occurs predominantly in

women of childbearing age

pathogenesis of SLE

Type III Hypersensitivity

nuclear components from apoptotic cells (from UV exposure or other factors) ->

APC -> CD4+ -> Th2 -(IL4)-> BC -> Plasma Cell -> IgG high affinity for dsDNA -> auto-antibodies in blood complex with nuclear antigens -> impaired clearance of apoptotic bodies and immune complexes -> cause complement (C2, C4) and (C3, C4) deficiency respectively

impaired clearance (deposition) of apoptotic cells & complexes -> malar rash, nephritis, vasculitis etc.

principle mechanism of injury of SLE

immune complex deposition in renal structures

renal structures

kidneys

thrombotic process in SLE involving..

glomerular capillaries and extraglomerular vasculature

thought to be caused by anti-phospholipid Ab

antinuclear antibody (ANA)

test to identify antibodies that attack the nucleus of the individual's own body cells (auto-antibodies)

Anti-dsDNA

are specific for SLE

Anti-smith is also specific for SLE

Anti-phospholipid antibodies

SLE (anti-dsDNA also)

Antiphospholipid antibody syndrome

ocular symptoms of SLE

Sicca Syndrome (Dry eyes and mouth)

Nonspecific conjunctivitis

More serious can cause blindness- retinal vasculitis and optic neuritis

systemic symptoms of SLE

fever, malaise, weight loss, anorexia

rheumatic fever

a bacterial infection that can be carried in the blood to the joints

RF is highest in what ages?

5-15

pathogenesis of rheumatic fever

1. Sensitization of B lymphocytes by streptococcal antigens

2. Formation of anti-streptococcal antibodies

3. Formation of immune complexes that cross-react with cardiac sarcolemma antigens

4. Myocardial and valvular inflammatory response

triggers of rheumatic fever

may develop if strep throat or claret fever infections are not treated properly

what causes rheumatic fever

group A streptococcus (group A strep)

in a small number of those with group A streptococcus, the M proteins in the bacterial capsule mimic normal heart antigens and induce Ab that also react with proteins in the _____, damaging it

heart

damaging the heart valve (type II)

some streptococcal skin/throat infections release bacterial Ag into the blood that form circulating immune complexes which may deposit in the kidneys and initiate...

an immune complex glomerulonephritis

type III

rheumatoid arthritis

a chronic autoimmune disorder in which the joints and some organs of other body systems are attacked

in the acute phase fluid is evident; in the later stages ____ of the joint may set in

ankylosis

epidemiology of rheumatoid arthritis

females > males

age onset - peak 35-45 years

Pathogenesis of Rheumatoid Arthritis

Type IV Hypersensitivity

Stress induced change from Arginine -> Citrulline in self protein that creates neo antigen -> APC -> CD4+ -> Th1 -> produce IL2, IFNy (migrate to joint & activate M0) -> M0 produce TNF, IL 6, IL 1, IL 8 -> inflammation.

Neo antigen -> BCell -> produces Anti-Cyclic Citrullinated Protein (Anti CCP present in 70% patients) antibody and IgM anti IgG antibody (RF) via Th2 cell IL 4 help.

ocular symptoms of rheumatoid arthritis

dry eyes

uveitis

scleritis

episcleritis

glaucoma

cataracts

systemic symptoms of rheumatoid arthritis

fatigue, malaise, weakness, weight loss, wasting, fever, and anemia.

diagnostic tools of rheumatoid arthritis

rheumatoid factor

ANA

rheumatoid factor

an IgM Ab seen in the sera of 75% of pt with RA

ANA (anti-nuclear Ab)

seen in 20% of pt with RA

anti nuclear antibodies

the gold standard test for detection of lupus is:

Sjorgen's disease

• destruction of salivary glands as an autoimmune response

• inhibit salivons & pt have dry mouth

Pathogenesis of Sjogren's Syndrome

combination of genetic and environmental factors cause lymphocytic infiltration and fibrosis of the lacrimal and salivary glands

genetic factors of Sjogren's Syndrome

most important is HLA-DR, which correlates closely with ANA and anti-SSA Ab

environmental factors of Sjogren's Syndrome

no single agent identitfied

viral candidates may include Epstein Bar virus (EBV) and Coxasckie viruss

hep c, HIV and HTLV-1 cna mimim

epidemiology of Sjogren's Syndrome

women around 59 years old

triggers of Sjogren's Syndrome

a combination of genetic, environmental and possibly hormonal factors

diagnostic tools of Sjogren's Syndrome

anti-SSA/Ro or SSB/La (50-90%)

+RF (90%)

increase in ESR (erythrocyte sedimentation rate)

Schirmer test

decreased tear production

positive in sjogren's syndrome

less than 10 mm of film -> abnormal

less than 5 mm wetting -> decreased tear production and sicca syndrome

systemic effects of Sjogren's Syndrome

dry eyes, dry mouth lymphoma

skin findings of Sjogren's Syndrome

nasal, vaginal and cutaneous dryness

GI symptoms of Sjogren's Syndrome

nausea, abdominal pain

ocular symptoms of Sjogren's Syndrome

dry eyes, blurry vision, burning, gritty feeling

myasthenia gravis

a chronic autoimmune disease that affects the neuromuscular junction and produces serious weakness of voluntary muscles

etiology of MG

-autoimmune

-antibodies are produced that attack the components of the muscle end plate

epidemiology of MG

age > 40

pathogenesis of MG

Ab to ACh-R at NMJx -> block neuromusc. transmission -> easy fatiguability

causes of MG

• insufficient secretion of acetylcholine

• excessive secretion of cholinesterase

• unresponsiveness of muscle fibers to acetylcholine

what type is MG considered

type II

MG results in (3)

1. decreased number of nicotinic AcH receptors at the motor end plate

2. reduced postpynaptic membrane folds

3. widened synaptic cleft

prognosis of MG

no cure, but significant improvement with treatment

some remission

lead normal to nearly normal lives