(17) Autoimmune Diseases Flashcards
What is autoimmunity?
Immunity that is specific for self-determinants
What is molecular mimicry?
Autoimmune disease caused because body molecule and pathogen molecule are very similar
T or F: there are no autoimmune diseases that involve IgE
True
What fail safes are in place to prevent us from producing autoimmune responses?
- Negative Selection in the Bone Marrow and Thymus
- Expression of tissue Specific proteins in the thymus
- No lymphocytes can access some tissues
- e.g Cornea and Testes - Suppression of Autoimmune Responses by Treg cells
- Induction of anergy in autoreactive B and T cells
What autoimmune diseases interfere with function of:
- Thyroid Gland
- Andrenal Gland
**What cell mediates these diseases?
Thyroid Gland: B CELL MEDIATED
- Hashimoto’s Thyroiditis
- Grave’s Disease
- Subacute thyroiditis
- Idiopathic Hyprothyroidism
Adrenal Gland: B CELL MEDIATED
- Addison’s Disease
What cell mediates Autoimmune diseases of the Islets of Langerhans?
- what are these diseases?
T cell Mediated - DIABETES
Type 1 Diabetes:
- Insulin-Dependent Diabetes
- Juvenile-Onset Diabetes
Type 2 Diabetes:
- Insulin-Resistant Diabetes
- Adult Onset Diabetes
What happens to Thyroglobulin when Thyroid Hormone is NOT Required?
- What about when it IS required?
Not Required:
- Thyroglobulin is stored in its Iodinated form
Required:
- Iodinated Thyroglobulin is cleaved into T3 and T4 and secreted from the cell
What happens to a child that has a mom with Grave’s at birth?
- what is done to protect the child?
- IgG that is TSH receptor specific will be present in the baby (b/c IgG can cross the placental barrier via Brambell receptor)
- Plasmapheresis is done at birth to remove all TSR specific Antibodies
What is Pyridostigmine?
Cholinesterase Inhibitor
**Used to Treat Myasthenia Gravis
What would you expect to see on an H and E slide of a glomerulus of a patient who has lupus?
Thickened Basement membrane
Why would fluorescence be a good method to look to see if a patient had lupus?
You can stain their glomerulus using fluorescent anti-human IgG, if the tissue fluorescence it means your immune system has been attacking that tissue with Ab
What would you expect to see in an H and E stain of the pancreas from a patient with insulin dependent Diabetes Mellitus?
ß-cell in the islets of Langerhans will be infiltrated with lymphocytes
How does Infliximab work?
- what disease is it commonly used to treat?
Infliximab:
- Anti-TNF alpha antibody
- Treats Rheumatoid Arthritis
How does Ritiximab work?
- what disease is it commonly used to treat?
Ritiximab:
- binds to CD20 on B cells which results in NK cells killing B cells via ADCC
- Treats Rheumatoid Arthritis
**Confusing because RA is typically thought of to be a T cell autoimmune disease
What general trend is observed regarding gender and autoimmune disease?
- what are the exceptions?
Women are MUCH more likely to get any kind of autoimmune disease than a male is
Except for:
- Ankylosing Spondylititis (men outnumber women)
- Psoriasis (men and women are equal)
- Wegener’s Granulomatosis (men and women are equal)
T or F: TCR inheritance is a strong predictor of autoimmune disease
FALSE, MHC inheritance is very strongly correlated to autoimmune disease
What is the significance of HLA-DR3?
MHC class II haplotype Strongly associated with incidence of production of AUTOANTIBODIES that interfere with:
- ENDOCRINE function
- NEURONAL signaling
What mutation has a Strong Association with Diabetes Mellitus?
Point Mutation at AA #57 of the HLA-DQ ß-chain
**This is strange correlation because HLA-DQ is an MHC class II, but this a CTL mediated disease
What are the Immunologically Privileged Site in the body?
- what makes them Privileged?
Sites:
- Eyes
- Testes
- Placenta
**These are functionally separated from the rest of the body so there antigens are localized ONLY to that site
Why would it be bad if a privileged tissue like the testes was exposed to a T cell?
Due to its functional separation there is no tissue available to use during thymic selection and therefore T cells that are reactive towards Teste tissue are highly likely to exist
**This of particular concern during trauma
Why don’t you have to worry about corneal injury causing host cell response to privileged tissue?
The cornea is avascular so it no lymphocytes would be able to get there
What is the significance of HLA-B27?
- disease?
Cross-Reactivity
- It presents antigens from MANY types of bacteria that mimic host proteins
- This leads to diseases like Reactive arthritis
What should you think when you see Campylobacter Jejuni?
Guillian Barre Syndrome
What treatment is often used for patients who suffer from chronic autoimmunity of blood cells (red or white)?
Splenectomy - this reduces the rate at which RBCs are destroyed
T or F: in pts. who have neutropenia from autoimmunity, the neutrophils are highly susceptible to MAC
False, nucleated cells are not that susceptible to MAC
T or F: HLA haplotypes often play an important role in the inheritance of autoimmune diseases
True, often Two Siblings that both have diabetes melitus each have the same haplotype
What HLA haplotype may predispose you to getting Goodpasture’s Syndrome?
HLA-DR2
What is a common variable among those who have Goodpasture’s Syndrome and experience pulmonary Hemorrhage?
- What process explains why is this observed in this group of people?
Smoking - those who experience this effect are often smokers
Why:
- 1st in non-smokers the basement membrane of alveoli is closed off from Abs.
- 2nd Smoking damages alveoli which compromises tissue integrity allowing Abs. in
Sympathetic Opthalmia
- what is it?
- What causes it?
- what does this indicate about privileged sites?
What is it:
- Immune system attacks the eye (anterior compartment)
Why:
- Damage to the eye can disrupt this normally immunologically privileged site allowing APCs to present antigens
- Since body has not be desensitized to this tissue it will attack it
- BOTH EYES get attacked
Indicates:
- PHYSICAL separation is not what protects these tissues
T or F: like the testes the uterus is also immunologically protected
True
