EX1 Tolerance/Autoimmune Disease - Powell Flashcards
physiological state in which the immune system does not react destructively against self tissues; it is LEARNED
self-tolerance
occurs in generative lymphoid organs (bone marrow/thymus) involving immature self-reactive lymphocytes encountering self antigen
central tolerance
in peripheral sites involving mature self-reactive lymphocytes encountering self antigen
peripheral tolerance
True or False
Tolerance is simply a failure to recognize an antigen
False; tolerance is an active response and is just as specific as an immune response
Tolerance can be _______ or _______
natural
induced
The most important aspect of tolerance is _____ ______; which prevents the body from mounting an immune attach against its _____ ______
self tolerance
self tissues
Immature T cells that recognize antigens with _____ _____ are deleted and some some reactive _____ T cells that see self antigens in the thymus are not deleted but instead differentiate into ________ ___ ____
high avidity
CD4
regulatory T cells
The choice between lymphocyte activation and tolerance is determined by;
the properties of the ________
state of ______ of the antigen-specific lymphocytes
types of _______ received when these lymphocytes encounter _____ _____
antigen
maturation
stimuli
self antigens
Central tolerance of B cells occurs the ___ _____; potentially auto reactive cells can be ______ or ______ by contact with _____ antigens
bone marrow
eliminated
inactivated
self
Central tolerance of B cells is achieved via _______ editing
receptor
VDJ rearrangement
______ and ________ of the self antigens determine the fate of B cells
nature and concentration
True or False
multivalent and high concentrations of antigens induce B cell death
True; lower concentrations induce functional anergy
_______ _______ is the mechanism by which mature T cells that recognize self antigens in peripheral tissues become incapable of responding to these antigens
peripheral tolerance (PT)
Mechanism of PT; actual elimination from the cellular repertoire by activation induced cell death
clonal deletion/apoptosis
Mechanism of PT; mature cell is present but its functionally inactivated (can be reserved)
clonal anergy
Mechanism of PT; inhibition of cellular activity through interaction with other cell (T-regs, etc.)
suppression
Mechanism of PT; coexistence of self-reactive clones and antigen; cells do not respond to antigen
ignorance
Factors determining which mechanisms are operative;
________ of self antigen in lymphoid organs
________ of antigen receptor for antigen
______ of the antigen
concentration and availability of _____ molecules
concentration
affinity
nature
co-stimulatory
True or False
Peripheral tolerance in B cells; NOT all potentially reactive cells are eliminated or inactivated and enter peripheral circulation
True
T cells affect the outcome of B cell activation in the periphery via the ____ _____ ____
two signal hypothesis
What are the two signals of the two signal hypothesis
- generated through the antigen receptor
2. mediated by CD40 and CD40L
If one of the signals from the two signal hypothesis is missing B cell ______ occurs
anergy (lack of reaction to the antigen)
Anergic cells show a block in _____ ____ signal induction; via lack of co-stimulation by _______ and co-stimulation by ____ _____
TCR-induced
B7/B72
inhibitory receptors
________ competes with CD28 for B7 and B72; it helps to keep the T cells in check
CTLA-4 (is an inhibitory receptor on T cells)
Knockout mice lacking CTLA-4 develop ______ lymphocyte activation, ______ lymph nodes and spleen, and ______ multi organ lymphocytic infiltrates
uncontrolled
enlarged
fatal
Self-reactive cells may be “deleted” from the repertoire via __________; activation in the absence of _____ can lead to death
apoptosis
IL-2
The state of tolerance may be maintained by ____ _____
immune regulation
How does ignorance happen;
antigen is expressed in a ______ _____
T cells cannot get to the antigen across an ______ _______
perhaps the antigen is not expressed in the context of ______ _____
immuno-privileged site
epithelial barrier
MHC molecules
Foreign antigens may be administered in ways that preferentially _____ _____ rather than immune responses
induce tolerance
True or False
Oral administration of antigen favors tolerance induction; a state of immune hypo responsiveness follows oral administration of an antigen
True
Five factors that lead to immunogeneicity or tolerogenicity of protein antigens include…
amount persistance portal of entry/location persistence of adjuvants properties of APCs
True or False
Mechanisms that lead to autoimmunity remain unclear
True
Seven factors can predispose an individual to various autoimmune diseases….
MHC associateions familial concordance (occurs in families) gender (women more likely than men) climate (equatorial less likely) chemical agents infectious agents immune dysregulation
What 3 things involving self-reactive cells initiates an autoimmune response
incomplete deletion
aberrant stimulation
altered regulation
True or False
Autoimmune disease can be systemic or organ specific
True
“Bystander activation” involves the induction of co-stimulators on ________ via up regulation of ________ resulting in autoimmunity
APCs
B7
_______ _______ results in a microbial antigen imitating a self tissue causing autoimmunity; this is more likely the case
molecular mimicry
An example of a systemic autoimmune disease is _____ and an example of organ specific autoimmune disease is _____
systemic lupus erythematosus (SLE) - kidney, heart, lungs, CNS multiple sclerosis (MS) - CNS
SLE produces _________ against self antigens such as DNA, nucleoproteins, lymphocytes, etc
autoantibodies
In MS, T cells are specific for components of the _____ ______
myelin sheath
