German - Adaptive Immune Diseases Flashcards
T/F - T cells play a huge role in autoimmune disease.
TRUE
What are autoimmune diseases?
Loss of tolerance leading to hypersensitivity reactions
Where are B cells negatively selected?
Bone marrow
*If interacts with self, it will rearrange if possible, or undergo apoptosis
**Central tolerance is it doesn’t react to self in marrow
**Once in lymph nodes, if it reacts to self, it becomes anergic
**If it doesn’t react to self, it has peripheral tolerance
Tell me more about autoimmune diseases (ADs).
Adaptive immune targeting of self
Humoral or cell-mediated
Often chronic and lifelong
Loss of self-tolerance
*All ADs are Type II, III, or IV hypersensitive
ADs can be caused by what?
Genetics
Environment
OR
Both (Majority of time)
T/F - ADs are among the 10 leading causes of death among women under 65.
TRUE
- Only 20% of predisposed individuals get autoimmune disease
- Infectious causes
- Non-infectious causes
________ _________ influences AD development.
HLA subtype
T/F - HLA genes associated with susceptibility in 50% of ADs.
TRUE
- Class II alleles most frequently implicated
- CD4 T cells closely tied to AD development
- Susceptibility does not always lead to disease
Tell me about Type II Hypersensitivity ADs.
IgG or IgM
Cell surface proteins
Agonist or antagonistic
Opsonization
Graves’, Hashimotos, Type 2 DM, Hypoglycemia
T/F - Rheumatic fever is caused by molecular mimicry.
TRUE
Strep pyogenes wall shares human episodes
- When body interacts with the cell wall, antibody response is activated
- These antibodies can cross-react with heart tissue, causing rheumatic fever
*T cells are necessary for prolonged autoimmunity
T/F - Graves’ disease is antibody binding causing metabolic dysfx.
TRUE
Tell me more about Graves.
Antibodies fx as a TSH agonist
CD4 Th2 Response
Excessive thyroid hormone release
Antibodies do not cause overt tissue damage
Tell me about symptoms of Graves.
Weight loss
Heat intolerance
Anxiety, irritability
Bulging of eyes (Exophthalmos)
Tx
-Ablatement to avoid overproducing T3 and T4
T/F - Antibody-mediated ADs can be temporarily transferred to newborns.
TRUE
Mother with Graves makes anti-TSHR antibodies
During pregnancy, antibodies cross the placenta into the fetus
Newborn infant also suffers from Graves’ disease
Plasmapheresis (filter out plasma removes maternal anti-TSHR antibodies and cures the infant’s disease
What is the opposite of Graves’ disease?
Hashimoto’s disease
Tell me about Hashimoto’s.
Destruction of normal thyroid tissue
CD4 Th1 response
HYPOTHYROIDISM
Growth of ectopic lymphoid tissue forms in the thyroid
-Enlarged, inflamed, under active thyroid (goiter)
Salivary gland enlargement
Compromised PD health
Macroglossia
Glossitis
Dysgeusia
Delayed dental eruption and enamel hypoplasia
Ant open bite, micrognathia, thick lips, mouth breathing
Is what?
Hashimoto’s disease
Increased caries
Increased susceptible PD
Enlargement of extraglandular thyroid tissue
Burning mouth syndrome
Accelerated dental eruption
Max and mandible osteoporosis
Dev of CT diseases like Sjogren’s syndrome or systemic lupus erythematosus
Is what?
Graves’ disease
Tell me about Sjogren’s Syndrome.
Progressive destruction of the exocrine glands
One of the most common ADs
- 0.5-5% prevalence
- 9 times more prevalent in women
- Utah has large population of this
*Type II hypersensitivity
Unknown initiating factors
Dry mouth, eyes, arthritis
-Prominent caries, oral candidiasis
Tell me about Type III ADs.
IgG mediated
Immune complexes
Rashes, kidney dysfx
Rheumatic diseases
Are diseases specifically one hypersensitivity or multiple?
Can be multiple
- Sjogren’s
- Rheumatic diseases
Tell me about Lupus.
Widespread self-antigen targeting and complex deposition
Unknown cause, potential environmental trigger
Deposits in bvs, kidneys, and jts
Epitope spreading leads to intracellular antigen targeting
Mouth ulcers and plaques
-Not necessarily painful at the onset
*Kidney dysfx
T/F - Lupus causes INTERmolecular epitope spreading.
TRUE
Cluster of nuclear proteins
Macromolecular complex presentation
Slowly expanding adaptive response
Loss of tolerance
Tell me about INTRAmolecular epitope spreading.
Self-epitope mimics a pathogenic epitope
Protein becomes a better antigen over time due to mimicry.
T/F - An individual with Lupus gets worse with time and multiple flare ups because the CD4 T cells involved get more sensitive over time.
TRUE
*One molecule spreads its loss of tolerance
Tell me about Type IV ADs.
CD4 and CD8 mediated
Contact hypersensitivity
Thymus involution tied to increased AD incidence
*Celiac disease
Tell me about Celiac disease.
Gluten is degraded in gut lumen to give resistant fragment
Fragment enters gut tissue and is delaminates by transglutaminase
Naive CD4 T cell responds to deaminated peptides presented by HLA-DQ
Inflammatory effector T cells cause villous atrophy
T/F - Type I DM is associated with autoimmunity.
TRUE
CD4 and CD8 T cell response kills pancreatic beta cells
Oral
- Reduced salivary flow
- Altered saliva composition
- Impaired wound healing
- Sweet breath
