Autoimmunity Flashcards
Define tolerance
a state of immunologic unresponsiveness to a particular antigen
goal of the immune response with respect to tolerance
- mount a response against non-self
- maintain unresponsive state toward self
when tolerance is broken
autoimmunity
dfine negative selection
when T cells recognize self and binds too tightly to self MHC
define positive selection
Recognize self MHC and bind it ; wont survive if cant
T reg cells
CD4+ CD25+
- express IL-2Ra chains (CD25) resulting in low affinity for IL-2
wherre to find Treg cells
secondary lymph tissues and sites of inglammation
- not that abundant (FEW) but powerful
what do Treg cells secrete?
IL-10 and IL-35 TGFb which are anti-inflammatory and suppress nearby responses
what does Treg cells inhibit
APCs
- they bind CD80/86 via CTLA-4 on T cells
bind APC along with other T cells = suppressing thier activity = LINKED SUPPRESSION
regulatory CD8+ cells
- not generated in thymus but in periphery during CD8+ T cell activation induction events
- not well understood
- use wide range of mechanisms like Treg to suppress activity
when do reg CD8+ cells appear?
after Ag-MHC I stimulation in the presence of TGF-B cytokine
CD8+ reg T cells mechanisms to suppress activity
lysis of APCs
inhibition of APC function
regulation of effector cells that bind the same Ag
this hormone promotes Th2 response to increase Ig levels
estrogen
- why females may have higher incidences of autoimmunity
Estrogen speeds up _____ cell production (extramedullary) so negative selection may be missed
B cell
drugs tha can cause autoimmunity
procainamide, hydralazine - lupus
methyldopa, quinidine - AIHA
infections that can cause autoimmunity
Coxsackie virus B - T1 diabetes
K. pneumonia - ankylosing spondylitis
environmental factors that can cause autoimmunity
drugs
infections
diet
chemicals/toxins
proposed mechanisms that can induce autoimmunity
multifactorial/several “hits”
- molecular mimicry
- infections that induce genetic changes
- damage/stress events that exposed sequestered Ag
- foods that alter gut microbial balance, promoting chronic inflammation and hypersensitivity rxns
- exposure to immune privileged sites (if damaged = can see things you weren’t exposed to in that site???)
- Th1 vs Th2 = unbalanced (more antibodies formed –> autoimmunity)
when autoAbs bind red cells and are removed in the spleen
AIHA
pernicious anemia
autoantibodies to intrinsic factor = no NO B12
- macrocytic anemia
idiopathic thombocytopenia
autoAbs bind platelets = removed in spleen
thrombocytopenia = bleeding, thrombosis
Goodpasture’s disease
- anti-basement membrane of glomeruli and alveoli
- complement activation
types of systemic autoimmunity disorders
SLE
MS
RA
lab diagnosis for autoimmunity
- ANA (anti-nucleic antibody)
> detects general antibodies to DNA, RNA, proteins - patterns of IF suggestive of antibody type
> homogenous = chromatin, dsDNA, hostones
> Rim = dsDNA
> speckled = RNP (Sm, SS-A, SS-B)
> nucleolar (nucleolar RNA)
challenges posed by autoimmunity treatment
reduce autoimmune BUT maintain alloimmune
Treatment challenges of autoimmune
Reduce autoimmune but maintain alloimmune
Anti inflammatory drugs
Non steroidal drugs (NSAIDs)
Corticosteroids
Pain control for autoimmune diseases
Acetaminophen
Immunosuppressive drugs
Azathiaprine
Cyclophosphamide
Cyclosporin
Antibody removal for autoimmunity
Plasmapheresis
IVIg for autoimmunity
Fc binding of macrophages
Inhibitory signalling via membrane binding of T, B and monocytes (reduces cytokine production)
Anticomplement vs procomplement
Anti-idiotypic antibodies
