Lecture 126 Flashcards
T-cells with medium to high affinity for self become ______
Treg cells
B-cells can modify their ____ if the original BCR is self-reactive
light chain gene
Peripheral tolerance mechanisms:
Self-reactive T-cells do not receive necessary co-stimulatory signals
What are the necessary co-stimulatory signals?
Clonal anergy
(CD28/B7)
Peripheral tolerance mechanisms:
Self-reactive cells exist but never encounter enough of their antigen or the right conditions to be activated
Immunological ignorance
Peripheral tolerance mechanisms:
Ex. depletion of IL-2 can help turn off T-cell proliferation
Cytokine withdrawal
Peripheral tolerance mechanisms:
Physical barriers or molecular signals controlling T-cell trafficking
Sequestration
Peripheral tolerance mechanisms:
Antibodies directed against self-reactive antibodies help regulate autoimmunity
Idiotype network theory
Peripheral tolerance mechanisms:
Specialized subset of CD4+ T-cells that suppress other immune cells
Treg cells
____ is the critical transcription factor for treg development and functions
FOXP3
Treg cells secrete ____, ____, ____, and deplete _____
IL-10, TGF-b, IL-35, and deplete IL-2
Clinical condition:
IPEX syndrome results from ____ gene mutations
Leading to ____
FOXP3
Severe autoimmunity
____ is an antigen-driven process requiring self-reactive lymphocytes
Autoimmunity
____ is an innate immune dysregulation, it is not driven by a loss of tolerance
Autoinflammation
The subclinical stage of autoimmune disease leads to ____
Epitope spreading
Mechanisms of pathogenesis:
Certain bacterial or viral proteins can nonspecifically active large nuumbers of T-cells, potentially including autoreactive clones
Superantigens
Mechanisms of pathogenesis:
Ex. autoreactive B-cells that fail to respond to normal inhibitory signals and thus continue to react with self-antigens
Defective receptors
Mechanisms of pathogenesis:
Structural similarity between microbial and self-antigens
Molecular mimicry
Clinical condition:
Cross reactivity between S. pyogenes antigens and cardiac myosin
Mechanism of pathogenesis:
Rheumatic fever
Molecular mimcry
Clinical condition:
Cross reactivity between C. jejuni antigens and peripheral nerve gangliosides
Mechanism of pathogenesis:
Guillain-Barre syndrome
Molecular mimicry
Mechanisms of pathogenesis:
Accelerated apoptosis increases release of self-antigens
Defective apoptosis
Mechanisms of pathogenesis:
Defects in clearing apoptotic cells lead to prolonged exposure of internal autoantigens
Related clinical condition:
Defective apoptosis
SLE
Mechanisms of pathogenesis:
Immune response broadens from the initial epitope to other epitopes once tissue damage exposes new self-antigens
Epitope spreading
Mechanisms of pathogenesis:
Self-antigens normally “hidden” become visible to the immune system after tissue damage or infection
Cryptic epitope exposure
Mechanisms of pathogenesis:
A self-antigen binds to a foreign molecule (virus particle, drug) and is presented as “foreign”
PF4/heparin complexes lead to:
Hapten effect
Heparin-induced thrombocytopenia
