review Flashcards
intraepithelial lymphocytes
resident lymphocytes in MALT
what do enterocytes respond to
PMAPs through intracellular TLR4
class switching to igA
can be TI and TD depedning on BAFF and april
what are the ways antigens can cross mucosal epithelial barriers
FcR
golet cells
m cells
direct APC contact
th1 response
two phases
inductive and effector phase
what response are alarmins a part of
th2
celiac disease first step
sensitiation: exposure to gluten peptides
igA antibodies in celiac
anti tTg
anti gliadin
anti endomysial
genetic component of celiac
HLA DQ2 and 8
Enviromental component of celiac
il15, 21 AND IFN a
alveolar macrophages
balance tolerance and inflamation in lung
what is the last step of a normal graft response
resolution
first and second set rejection timeline
12-14 days
5-6 days
what cells play a role in graft rejection
cd4 and 8
cd4 more important
anti cd4 and 8 keeps the survival of graft for much longer
what are the stages of graft rejection
sensitization
hyperactute
acute
effector
chornic
recognize peptides from donor MHC on self apc
INDIRECT RECOGNITION
recognize donor MHC
direct recognition
effector stage
heavy infiltation of recipient cells
neutrophils
DC
macrophages
ADCC
complement
CD4,8+
inc in lytic enzymes and MHC
inc in membrane damage and cytotoxicity
lysis
NK cell
-directly damage by lysis or apoptosis
rarely Ab against donor HLA and endothelial ag
when does hyperactute rejection occur
before tissue revascularizes
within 24 hrs
acute and hyperacute mediated by what
acute- cd4 t cells
hyperacture- ab
mechanism of acute rejection
massive infiltration of lymphocyte and macrophages and effector stage
mechanism of chronic rejectino
ab or cell mediated
when is total lymphoid irradiation used
bone marrow transplant and graft vs host disease
azathioprine
mitotic inhibitor diminishes b and t cell proliferation
general immunosupresive therapy
azathioprine and cylophosphamide and corticosteroids
specific immunosupressive therapy
bellatracept- CTLA4 fusion- induces t cell anergy
OKT3- CD3 mAb that depletes t cells
where does central tolerance occur
in primary lymphoid organs
where is AIRE expressed
mostly in lymphoid organs
what does positive selection
thymic epithelial cells
disease for absence of AIRE
autoimmune polyendocrine syndrome 1 APS1
where are self reactive B cells deleted or inactivated
in the bone marrow
what are the methods of peripheral tolerance
anergy/ unresponsiveness due to lack of costimulation
apoptosis through fas/fasL
what forms self reactive b cells
SHM in the germinal centres
molecular basis of t cell anergy
only get signal one from antigen - anergy and no iL2 expression
activation of fas receptor known as
ACID
activation induced cell death
anergic b cells also express fas
people w mutated fas
ALPS
autoimmune lymphoproliferative syndrome
mice w mutated fas and fasL
lpr and gld
inc in autoimmune diseaeds and lymphocytes
what initiates oral tolerance
encounter of food ags with GALR
-enters circulation and taken by APC and shown to T cells without B7 costimulation leadnig to T cell anergy
- gut microbiome plays a role
etiology of autoimmunity
genetics
-family clustering
-HLA and non HLA associated
environmental
-microbial antigens and trauma
mix of environmental and genetic
drug and hormonal triggers
polyclonal activation
encountering PAMPs like LPS on gram -ve bact interacts w activating receptors
activates many clones
intracellular detection of pathogenic patterns of DNA
what are the types of enviromental suscpetibility
sequestered antigen
molecular mimickery
polyclonal activation
inapproperiate expression of class II MHC
what transfers autoimmunity
CD4+
TH1 polarization inc autoimmunity
specific HLA alleles
must have trimolecular complex interaction
and lack of T reg (linked supression)
autoimmunity treatment
immunosupressive
-immmunosupressants
-anti inflamatory
-anti CD4
targetted therapies
block only ag activated T cells
targetted therapies for autoimmune diseases
anti cytokine ab or blockers
-block TNFa
-embrel, rumicade, humira
-RA, crohns, ankylosing spondylitis
ritixumab
-mAb against CD20 inducing apoptosis and ADCC
-RA
challenge of only blocking activated T cells
must only block activated ones
-mAb against ILRa subunit
-potential neg effect on Treg
block specific associated TCR chains
