autoimmunity Flashcards
➢ — = Failure of immune system to
respond to antigen
➢ —- = Failure of immune system to
respond to self antigen
➢ Failure of self-tolerance results in —
tolerance
self tolerance
autoimmunity
➢ —- means that autoantibodies and/or autoreactive T cells are present, without detectable organ
dysfunction or inflammation.
- Common in :
➢ —
➢ —-
➢ — reactivity with intercurrent illness.
autoimmunity reacitvity
women
older ppl
non specific
Autoimmune disease is present when there is(or has been) — , usually associated with – , driven by the — immune system in the absence of — stimuli
- who can get it? —-
- — and — factor at play
- more common in —
- — or —- of one autoimmune disease increases the risk of another
inflammation
organ dysfunction
adaptive
external
everyone can get it
genetic n environmental
pre meno women
personal or family history
how is the tolerance mediated :
➢ — “education”
➢ — tolerance
➢ Absence of — signal
➢ Active —
➢ — tolerance
thyme
peripheral t cell
signal 2/danger
regulation
b cell
—- reduces the risk of autoimmunity
negative selection ( check slide 9,10,11)
b cell tolerance :
➢ Failure of — help
➢ —- (Immature B cells)
- — (multivalent self-antigen)
- — ( soluble self-antigen)
➢ — (mature B cells)
- — (multivalent self-antigen)
- — (soluble self antigen)
t cell
bone marrow
deletion
anergy
periphery
deletion
anergy/deletion
in autoimmuity :
➢ Common – tolerance is “ — ”
➢ Autoimmune —
➢ Autoimmune —
leaky
reactivity
disease
( check slide 14)
rheumatic fever is an — illness
which occurs — after a group —–
- molecular mimicry of —
acute systemic inflammatory illness
2-4 weeks
group A beta heamlytic streptococcal pharyngitis
heart muscle, valves,articular structures & neurones
rheumatic fever clinical features:
➢ Fever
➢ Migrating arthritis
➢ Destructive inflammatory lesions
myocardium
endocardium& heart valves
pericardium
Periarticular structures
Subcutaneous tissues
➢ Chorea
jones criteria od rhemtic fever:
—:
Carditis
Polyarthritis
Erythema marginatum
Sub cut nodules
—- :
Fever
Arthralgia
Rheumatic fever
- diagnosis : 2 major or 1 major + 2 minor and evidence of —
major
minor
streptococcal infection
rf longterm sequelae :
➢ Valvular Heart Disease
➢ Increased risk of endocarditis
➢ Chorea may be persistent
( chrck slide 20 )
alteration of self:
self ( ex: dna) + drug ( ex: hydralazine ) –> —- –> bypass — –> —- —> occasionally persist when drug —
altered self
bypass tolerance
autoimmune reactivity
stopped
autoimmunity - superantigen :
*Activate large percentage –
*Overwhelm — mechanisms
* — syndrome
T cells
regulatory
kawasaki
infection of anitgen presenting cells:
➢ Signal 1 : —- and —
➢ Signal 2 – —
- Usually —
- Infection may activate
— / – & produce —
➢ Insulin – dependent –
➢ ? Role of viral infections
self anitgen and MHC class 1
costimulation
absent
dc and macrophages
signal 2
dependent DM
autoimmunity- mutaitons in gene controlling immune response:
➢ —- syndrome – ALPS
➢ Mutations in — ligand
➢ Prevents lymphocyte –
➢ Immune responses cannot be switched –
➢ Equivalent to lupus prone mouse
Autoimmune lymphoproliferative
Fas/Fas
death
switched off
Occur when a particular organ, is the sole target of the immune response.
➢ Examples:
o —
o —
this is known as
organ specific autoimmune disease
autoimmune thyroid disease
myasthenia gravis
Occurs when the autoantigen(s) are not tissue-specific, and the immune response can damage several organs
➢ Examples:
o systemic lupus erythematosus
o rheumatoid disease
this is known as
non organ specific autoimmune disease
mechanisms of tissue injury :
Type — Hypersensitivity
➢ Humoral immunity to tissue components
Type — Hypersensitivity
➢ Immune complex deposition
Type — Hypersensitivity
➢ Cellular immunity to tissue
Indirect antibody effects
II
III
IV
— are produced in many autoimmune diseases
➢ In some cases they play a — role
➢ In others they do not, epi-phenomena
➢ They may be useful a – test which are useful if they help :
autoantibodies
pathogenic
laboratory
useful if:
➢ To rule in a diagnosis
➢ To rule out a diagnosis
➢ To monitor disease activity
➢ False positive and false negative results are common
➢ There is not a test for everything – clinical diagnostic
skills essential
autoantibodies in diagnosis:
➢ Rule out a diagnosis
➢ Need — test – pick up most with disease
➢ —- (CTD) screen
➢ If negative CTD unlikely
➢ Not very – – if pos only 60% have CTD
➢ Several subtypes of CTD – pos screen doesn’t tell you which one.
➢ Need further — tests to rule in CTD
➢ Anti-RNP pos in > 98% with mixed connective tissue disease
sensitive test
connective tissue disease screen
specific
specific tests
autoantibodies in monitoring:
➢ — disease
➢ Monitor response to –
➢ If develop ESKD only consider transplant if anti-GBM level is undetectable.
Anti-GBM
therapy
How good is a test at helping me
diagnose a patient?
Terms to describe assay —
diagnostic performance
test performance includes;
➢ — - how close is result to gold standard
➢ — - does test give same result each time
➢ —
➢ —-
➢ —- intervals
➢ —-
➢ —-
➢ What can —- with the test
accuracy
precision
sensitivity
specificity
reference intervals
cut offs
interception
interference
❖True — ( —) - % with disease who
have positive test result
❖True – ( —) - % without disease
who have negative test result
❖False— - % WITHOUT disease who have Positive result
❖False — - % WITH the disease who have NEGATIVE test result
true +ve ( sensitivity )
true -ve ( specificity )
+ve
-ve
— refers to % of patients with the disease who have a positive test
formula: true +ve / all ppl w disease ( true +ve and false -ve)
— refers to % of patients who do not have the disease who have a negative test
formula : true -ve / all patient who don’t have the disease ( tn + fp)
— refers to % of people with a positive test who turn out to have the disease/condition
— refers to % of people with a negative test who do not have the
disease
clinical sensitivity
clinical specificity
+ve predicitive value PPV
-ve predicitve value NPV
- – % of people with a positive test who have the disease being tested for
depends on — chose for the test ad on – of the disease in the population being tested - — refers to % of people with a negative test who do nothave the disease being tested for which depends on — chosen and affected by – of the disease in the population test but — than PPV
positive predictive value PPV
cut off
prevalence
negative predictive vale NPV
cut off
prevalence
less
( check slide 40,41,44)
How many patients are correctly classified by the test refers to —
TP + TN ( correct results ) / TP + FP + TN + F ( all results )
diagnostic efficancy
impact of indiscriminate testing:
False positive results create — & — to patient
-unnecessary tests
- may get inappropriate treatment
- delay getting correct diagnosis
- false positive allergy tests can cause harm
is also –
– test results for patients who need them
summary of the lecture :
Breaches of tolerance are common, however
only cause disease in a minority.
➢ Some mechanisms of autoimmunity are
understood – usually cannot explain
mechanism
➢ Understanding test performance is the first
step in interpreting a result
anxiety
risk
cost
delay
