12f. Immune Health - Autoimmunity Flashcards
What is autoimmunity?
Immune system mistakenly attacking the body’s own cells
Why is AI present in healthy individuals?
To eliminate degraded self antigens
When does the elimination of degraded self antigens become pathological?
If there is a breakdown in self tolerance
What are the pathophysiological reasons for AI?
Tolerance
T-helper cells
Cross-reactivity
MHC dysfunction
What happens in AI with self tolerance?
Usually self-reactive lymphocytes and T-cells are deleted
However, some T-cells may be released early into circulation before being fully exposed to self-antigens
Also may be too few T-reg cells to manage autoreactive T-cells
What role do Th1, Th2 and Th17 cells have in AI?
Th1 increases macrophages in Crohn’s
Th17 increases inflammatory cells
Th2 cells are dominant in systemic conditions (SLE, Sjogren’s)
What is involved in cross-reactivity?
Mimicry - an antigen looking like a self-antigen
Tissue damage from a previous infection which releases self-antigens
What is the role of the Major Histocompatibility Complex?
Encodes cell surface proteins (HLAs)
Antigen presentation
Prevention of immune system targeting own cells
(Dysfunction is associated with AI)
Why are bacteria implicated in AI?
May have a similar structure that can fit on an epitope of an antigen
Which bacteria is implicated in RA, MS, SLE?
EBV
How can we get cross-reactivity in foods?
Peptide sequences in foods may be similar to human tissues
Molecular mimicry can induce or exacerbate AI diseases
Examples of foods where peptide sequences can mimic certain molecules
Wheat
Dairy
How can food toxins become more reactive?
May be modified by toxins
What is epitope spreading?
Antibody and cellular response to a given antigen may extend from one epitope to others
What is bystander activation?
Infections activate APCs such as dendritic cells which activate autoreactive T-cells
What are cryptic epitopes?
Some self-epitopes are hidden from immune recognition
If produced in large quantities, AI T-cell reactions may occur
Causes and risk factors for AI
Genetics
Emotional trauma
Infection
Gluten
Environmental toxins
Vit D deficiency
Dysbiosis
Intestinal permeability
Gender
Hormonal imbalances
Examples of SNPs that disrupt antigen recognition/self tolerance
HLA-DRB1
HLA-DQA1
HLA-DQ8
Examples of SNPs predisposing to inflammation increase
TNF
IL-2
IL-12
Examples of SNPs that affect vit D conversion
VDR
CYP24A1
CYP27B1
Why is gluten a cause/risk factor for AI?
Key food source of molecular mimicry
Inducer of intestinal permeability
Why are environmental toxins a cause/risk factor for AI?
Induce OS
Contributes to immune intolerance
Why is a vit D deficiency a risk factor for AI?
Vit D increases T-reg cells
Maintains self-tolerance
Why is dysbiosis a risk factor for AI?
Creates too much cross-talk between GI microbes and wider immune system
