Immune Cells as Villains Misdirected Immune Attack During Autoimmune Diseases

Immune Cells as Villains Misdirected Immune Attack During Autoimmune Diseases

Cells of our immune system often serve as “heroes,” playing protective roles in our bodies against
various pathogens and diseases. However, failure of tolerance to self-antigens elicits “villainous”
immune activity by an individual’s T cells and antibodies, resulting in destructive tissue damage and
disease. These misdirected immune attacks are called autoimmunity, and the diseases they cause are
called autoimmune diseases.
Autoimmune diseases, like allergic reactions, are more common in countries with more prosperous
economies. The incidence of autoimmune diseases in these countries has steadily increased over the
last 80 years and is largely explained by the impact of lifestyle and a hyper-sanitized environment on
the immune system. Researchers are trying to elucidate what makes some people more susceptible to
autoimmunity. Genes that control self-tolerance mechanisms play an important part, but a trigger is
necessary to prompt the autoimmune process. The main culprits are viral infections, and data from the
current Covid pandemic have reinforced this idea. However, changes in microbiome composition are
also starting to emerge as possible contributors to autoimmune susceptibility. Autoimmune diseases
are generally more common in women than in men but the reasons for this observation are unclear.
Various immune effectors, mainly autoantibodies and autoreactive T cells cause tissue injury in different
autoimmune diseases. The clinical manifestation of the disease depends on whether the site of the
autoimmune attack is localized to a particular organ/tissue or is more systemic. Autoimmunity tends to
be discovered after years of the initial immune attack when the tissue damage has escalated to cause
a disease that becomes chronic and self-perpetuating since the target of immune attack are self-antigens
that cannot be eliminated.
Format: 5-6 pages long (max 1800 words); double-spaced; 1-inch margins; 12 pt Times. Your paper
can refer to any assigned course content (required/recommended readings (e.g. papers, textbook),
references provided on slides) or additional references that you find on your own. Please do not
reference lecture slides.
Assignment Content
The assignment can be approached in several ways, including (but not limited to):
1. Focus on the mechanisms governing tolerance to self: elimination of autoreactive clones during
lymphocyte development; induction of ‘anergy’; function of regulatory T cells (Tregs);
engagement of inhibitory molecules such as CTLA-4. Gene variants that abrogate or impair the
function of these regulatory processes should be at least mentioned.
2. Focus on genetic susceptibility to autoimmune disease. This focus can be seen as a
variation/extension of point 1 and should focus on susceptibility genes that have been identified
in family studies and genome-wide association studies (GWAS), including HLA and non-HLA
genes.
3. Focus on environmental factors which are thought to act as triggers of autoimmune attacks in
susceptible people. These should include the role of viral infections (of which a focus of its own
could be ‘long Covid’ and autoimmunity); sex hormones; microbiome imbalance

4. Focus on a particular disease, e.g., multiple sclerosis or type I diabetes. In this focus, your
paper should provide context by including an introduction where points 1-3 are summarized in
half to one page.
5. A ‘holistic approach’ where points 1-3 are all explored in some depth, as per word limits.
6. Focus on the treatment of autoimmune disease. In this focus, your paper should provide context
by including an introduction where points 1-3 are summarized in half to one page. It can include:
A. conventional immunosuppressive therapy; B. monoclonal antibodies targeting specific self-antigens,
blocking inflammatory cytokines, blocking immune cell trafficking, blocking costimulatory
pathways; C. therapies to restore tolerance; D. more experimental therapies
including the creation of personalized Tregs.