Multiple sclerosis
Chronic autoimmune disease of the** central nervous system**
Destruction of myelin sheath around neurons
→ lesions can be seen by MRI
Nerves cannot properly pass along their
signals (sclerosis = scar tissue)
MS
range of symptoms
- pain
- fatigue
- tingling麻刺感
- impaired gait (pattern of walking)
- vision problems
- bladder problems
- dizziness
- cognitive and mood problems
- paralysis瘫痪
MS and immune system
Inflammation causes increased recruitment of other immune cells
Lymphocytes cross the blood-brain barrier and autoreactive CD4+ T cells reencounter their specific autoantigen presented by MHC II on macrophages
Autoreactive T cells, B cells and innate cells lead to demyelination
Treg can regulate the inflammation for a bit
unknown trigger, microglial express the self-peptide recognize by the autoimmune T cells
MS
() express the self peptide
microglial
MS
() produce myelin and support neurons
oligodendrocyte
type of MS
~ 85% of patients suffer from relapsing-remitting MS: experience periods when symptoms get better (remission) followed by attacks (relapse)
relapsing-remitting MS
primary progressive MS
progressive-relapsing MS
secondary progressive Ms
MS
Episodes of relapses (attacks) which may or may not leave permanent disability followed by periods of remission
Relapsing-remitting MS
MS
Steady increase in disability with no relapse or remissions
Primary progressive MS
MS
steady increase in disability with
subsequent relapses and no remissions
Progressive-relapsing MS
MS
Initial relapsing-remitting MS that begins to
steadily increase in disability without periods of remission
Secondary progressive MS
Diagonosing MS
- MRI
- Vision, coordination, sense of balance
- Spinal Tap or Lumbar puncture – collecting cerebral fluid to determine how much inflammation is in your CNS
- Blood test – to rule out other diseases that might have similar symptoms
- Evoked potential tests – electric signals used to measure how quickly and accurately the nervous system responds
MS
treatment
reduces relapses by ~30%
weekly injection
* IFN beta therapy
* corticosteroids therapy
reduces relaspses by 50%
oral pills
more recent therapy
fewer side effects
* dimethyl fumarate therapy
MS
IFN beta therapy potential mechanism
- Control the secretion of pro and anti inflammatory cytokines
- Reducing the ability of lymphocytes to cross blood-brain barrier
- Affecting APC function
- May inhibit some T cell differentiation & increase T cell apoptosis
MS
corticosteriod therapy
immunosuppressant → reduces inflammation
caused by pro-inflammatory cytokines, increases induction of apoptosis in
lymphocytes, reduces migration of leukocytes to the brain
have risk to the patient because caused immunocompromised
MS
dimethyl fumarate therapy
- Anti-inflammatory effects: can suppress the production of pro-inflammatory cytokines
- Stimulate Tregs
- Induce changes in maturation, availability and antigen-presenting capacity of APCs
other therapy of MS
Various components of the immune system are targeted by these MS therapies, which can lead to immunosuppression
many factors can contribute to MS progression
smoking
pathogens
gut microbiome
lipids and lipoproteins
hypertension
genetics
diabetes
diet
physical inactivity
body mass index
ITP
immune thrombocytopenia
an acquired autoimmune disorder in which the body’s immune system destroys healthy platelets, leaving the patient at risk for spontaneous bleeding and bruising (挫伤)
Cause of ITP
evironmental exposures (viral infection, vaccine, toxins, stress)
genetic predisposition (mutation family)
loss of immune self-tolerance (antigen mimicry, dysfunction of Tregs, anti-platet IgG antibody)
pathophysiology病理生理学 of ITP
increased platelet destruction: B cell make antiplatelet antibodies, platelet moved
decreased platelet production: CTL destroy the megakaryocytes in the bone marrow, magakaryocytes produce platelet
=low platelet
epidemiology 流行病学 of ITP
- ITP affects ~5 in 100,000 children per year
- Most commonly between age 2-5 years
- Will often self-resolve within 3-12 months
- No way to predict who will be acute vs chronic
prevalence of adult with ITP at any time: 9.5 cases per 100,000
signs and symptoms of ITP
Purpura (bruising)
Petechiae
Nosebleeds
Heavy menstrual bleeding
Bleeding in the mouth or gums
Blood in emesis, urine or stool
Fatigue
Rarely, intracranial bleeding
The patient could also be asymptomatic!
lab finding of diagnosis of ITP
CBC and smear:
➢ Platelet count < 100 x 109/L
➢ Normal WBC, normal Hb, normal cell morphology
➢ Anemia only present if severe bleeding
major causes of ITP in children
Primary ITP
Primary immune deficiency or immune dysregulation disorder (PID)
Inherited Platelet Disorders (IPD)
