Autoimmunity Flashcards
d:autoimmunity
the presence of immune responses against self-tissues/cells
what is harmless autoimmunity?
Low titres of auto-antibodies or auto-reactive T cells
what is harmful autoimmunity?
High titres of auto-antibodies or auto-reactive T cells
Significant tissue/organ damage
Chronic inflammation
If antigen reeceptor gene rearrangement is unsuccessful what occurs in immature T+B cells?
No antigen-specific receptor expression immature cells killed
If Successful antigen receptor
gene rearrangement occurs, how does this lead to autoreactive T+B cells?
Surface expression of
functional antigen-specific receptors
(DO bind self-antigen)
How does the immune system deal with the presence of autoreactive T+B cells?
Specific ‘tolerance’ mechanisms are required:
Deletion of self-reactive lymphocytes in primary lymphoid tissues (central tolerance)
Inactivation of self-reactive lymphocytes in peripheral tissues that escape central tolerance (peripheral tolerance)
e.g. Regulatory T cells (TREG cells)
d: T regulatory cells
role in regulating or suppressing other cells in the immune system
f: Tregs
Regulatory T cells are crucial for the suppressing hyper-reactive or auto-reactive T cells
how do Tregs carry out their function?
Via production of anti-inflammatory cytokines
describe the pathogenesis of autoimmune diseases
Genetic susceptibility combined with an initiating event, leads to a loss of immune regulation, activating autoreactive B and T cells
describe the pathogenesis of autoimmune diseases
Genetic susceptibility combined with an initiating event, leads to a loss of immune regulation, activating autoreactive B and T cells
Name the other genes that makeup a complex genetic factor the most autoimmune diseases come from
HLA genes
sex determining genes
other immune response genes
symptoms of IPEX disorder
Severe infections Intractable diarrhoea Eczema Very early onset insulin dependent diabetes mellitus Autoimmune manifestations
treatment of IPEX syndrome
Cure: hematopoietic stem cell transplantation (HSCT)
Supportive care: immunosuppressive drugs
plus total parental nutrition
What gene in IPEX syndrome contains the mutation? Why is this a problem?
Mutation in FOXP3 gene, which is essential for the normal development of regulatory T-cells
Why are only males affected by IPEX?
the condition is X-linked
How can T cells only recognise peptides antigens?
when their presented by Major Histocompatibility (MHC) molecules
what are HLA genes aka and stand for?
MHC molecules in humans are also referred to as HLA (Human Leucocyte Antigen) molecules
Name some class I molecules on a nucleated cell?
HLA-A HLA-B HLA-C
Name some additional Class II molecules expressed by Specialised antigen-presenting cells
HLA-DR, HLA-DQ and HLA-DP
How many variants of HLA molecule types does each individual possess?
2
Why are HLA molecules highly polymorphic?
Proteins are processed into many component peptides
Different HLA molecules bind to different subsets of peptides
To maximise the net ability to bind all antigenic peptides:
Multiple different subtypes of HLA molecules
Individual HLA molecules exhibit significant allelic diversity
What is the theory behind the influence of HLA genes in autoimmune disease?
if an individual has pre-disposed HLA alleles, there is a selective presentation of disease relevant self-peptides
Name some people who are at a greater risk of autoimmune disease
women of childbearing age
people with a family history
people who live in a certain environment eg sunlight, chemicals etc
different races
Name some environmental factors that can contribute to autoimmune disease
Infection
Cigarette smoking
Hormone levels
d:molecular mimicry
is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides
What bacteria causes toxic shock syndrome? What does the syndrome do?
Staphylococcal proteins
Clostridium endotoxin
These can re-activate autoreacvtive T cells that have been inactivated by regulatory T cells
What type of antigen are the Staphylococcal proteins and
Clostridium endotoxin?
superantigens
Name some autoimmune diseases that are mediated by type II hypersensitivity mechanisms in the kidneys and the endocrine system?
k- Goodpasture’s syndrome
E- Graves disease
What is graves disease?
A leading cause ofhyperthyroidism
Auto-antibodies are generated that bind to the thyroid stimulating hormone receptor (TSHR
Name an autoimmune disease mediated by type 3 hypersensitivity reactions?
Systemic lupus erythematosus (SLE)
Symptoms of SLE
Skin rashes, nephritis,(inflammation of the kidney’s) alveolitis
pathogenesis of SLE
apoptotic bodies aren’t cleared due to SLE, leading to Increased cell death (apoptosis)
Decreased phagocytosis of apoptotic bodies
Decreased solubilisation and clearance of immune-complexes
Loss of tolerance (no suppression of auto-reactive B cells, production of auto-antibodies that recognise dsDNA and other nuclear self-antigens
Name a common autoimmune disease mediated by type IV hypersensitivity mechanisms and complications of it
Rheumatoid arthritis (self- antigen = ) Complications: inflammation in the lungs and heart
what are Th17 cells?
are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differentiation
