Autoimmunity Flashcards
Autoimmune diseases operate by what types of hypersensitivity?
- Type II - cytotoxic
- Type III - immune complex
- Type IV - T-cell mediated/delayed
What causes autoimmunity?
- Developmental regulation disfunction
- Genetics
- Environment
NO ONE FACTOR CAN CAUSE AUTOIMMUNITY
Mutations in what gene(s) is the most common genetic determinant of autoimmunity?
HLA - MHCI and MHCII
11% of caucasian people have the HLA-A1-B8-DQ2-DR3 haplotype, which is more likely to _______
bind self-antigen, thus predisposing them to autoimmunity
What are the 3 “immune-privileged” sites of the human body?
- Corneas
- Brain
- Testes
What is the only autoimmune disease that is more common in men than women?
Ankylosing spondylitis
What is the normal function of the autoimmune regulator (AIRE) gene?
Production of self-antigen to aide in negative selection
What is autoimmune polyglandular disease (APD)?
- Autoimmune response against many endocrine glands
- hypoparathyroidism
- adrenal failure
- ovarian failure
- type I diabetes
- candidiasis
- enamel hypoplasia
- nail dystrophy
What are the mechanisms that contribute to central tolerance? (3)
- Negative selection of B cells in the bone marrow
- Expression of tissue-specific proteins in the thymus so that they participate in negative selection of T-cells (AIRE)
- Negative selection of T-cells in the thymus
What are the mechanisms that contribute to peripheral tolerance? (3)
- Exclusion of lymphocytes from immune-privileged sites
- Induction of anergy in autoreactive B and T cells that reach the peripheral circulation
- Suppression of autoimmune responses by regulatory T-cells
Mutation of the X-linked FoxP3 gene causes a rare immunodeficiency that principally affects boys, called _______
immune dysregulation, polyendocrineopathy, enteropathy, X-linked disease (IPEX)
Children with IPEX have normal levels of _____ cells and elevated levels of ______ cells
- CD25 T-reg cells
- TH17 cells
How does IPEX present clinically?
- Enteritis → chronic diarrhea
- Type 1 diabetes
- Eczema
- Failure to thrive
- Do not survive past 1 y/o
_____ tolerance is negative selection during lymphocyte development, occurring in primary lymphoid organs
Central tolerance
_____ tolerance refers to anergy or suppression of auto-reactive cells; occurring in secondary lymphoid organs
Peripheral tolerance
True or false, peripheral tolerance only occurs after infection occurs.
True
What is the consequence of a T-cell failing to receive a co-stimulatory signal from B7 on APCs?
Anergy
Binding of pathogen to self-protein results in _____
pathogen creating a unique epitope for autoimmunity to occur
How can disruption of cell tissue or barrier result in autoimmunity?
Unregulated release of cellular contents (self-antigen) can activate nontolerized lymphocytes
What is molecular mimicry?
Pathogen antigen resembles host antigen, which triggers production of cross-reactive antibodies or T-cells
How do superantigens elicit an autoimmune reaction?
Stabilization of the MHC-TCR complex without the need for a co-stimulatory signal, thus activating potential auto-reactive T-cells
Describe the Bystander effect in regard to B and T cells.
Self-reactive B/T cells receive second signal for activation from nearby cells
Grave’s disease is associated with mutations in what gene?
HLA-DR3
Describe the mechanism of Grave’s disease
Auto-IgG are generated against TSH receptor, however these antibodies are agonistic so they cause activation of the receptor and cause chronic overproduction of T3 and T4
