Immuno-endocrinology Flashcards
Thymus, thyroid and bone
The thymus declines in time. How many percent remains and can enlarge again?
10%, can enlarge again
What happens with the feedback system when testosterone levels are very high?
Suppression of pituitary stimulating hormones
Name an example of a hormone that is produced by the thymus
LH
Why do you need your thymus for selection?
Selection between self- and non-self
You have to get rid of more then 90% of your lymphocytes, why? (2)
- Autoreactivity
- Bind with too much affinity to their receptor
How do you call an autoimmune disease in which the endocrine system is involved?
Polyendocrine autoimmune disease
Name and autoimmune disease in which a genetic defect affects the thymic function
Polyglandular autoimmune syndrome
In what process in substance P involved?
Pain
In which diseases does substance P play a role? (5)
- Migraine
- Chronic obstructive lung disease
- Arthritis
- Cystitis
- IBD
What does the ‘P’ in substance P stand for?
Powder
Substance P is produced by?
Neurones
What is the advantage of radio labeling substance P?
When the peptide goes to search for its receptor and finds it, accumulation of radioactivity happens which can be imaged
Name an example of connection between your neural- and immune system
Radiolabeled substance P that is released by neurons bind to receptors in the thymus
What is the function of somatostatin?
Excites brain, but inhibits the release of hormones
What is special about the receptors for somatostatin and cortistatin?
They are also expressed in the immune system (Thymus, and often spleen)
What happens to the receptors for neuropeptides during the development from stem cell to effector cell in the thymus?
They change
Name and example of immune cell type that can be stimulated by neuropeptides
Thymocytes
Which kind of dysregulations are associated with an enlarged thymus (thymoma)? (2)
- Immune dysregulation (including humoral and cellular immunodeficiency and autoimmune disease)
- Endocrine dysregulation
Which three categories of thymoma’s occur in humans?
- Lymphocytic
- Epithelial
- Mixed
Which catagory of thymoma occurs the most in humans?
Mixed
Which genetic defect is causing polyglandular autoimmune syndrome?
Autoimmune regulator (AIRE) deficiency
What can cause enlargement of the thymus during autoimmune disease?
Stimulation of the thymus by (for example) overproduction of thyroid hormones
Grave’s disease stimulates/inhibits your thyroid?
Stimulates
What is good syndrome?
Rare association of thymoma/increased thymus and immunodeficiency (immune dysregulation syndrome)
Immune dysregulation consists of.. (4)
- Immune deficiency
- Auto immunity
- Allergy
- Auto-inflammation
Name clinical manifestations in Good’s syndrome (4)
- Thymoma
- Infections
- GI disease
- Autoimmune disease
The principal immunological findings in Good’s syndrome are… (6)
- Hypogammaglobulinemia
- Few or absent B cells
- Abnormal CD4:CD8 ratio
- CD4 T cell lymphopenia
- Impaired T cell mitogenic response
- Cutaneous anergy
During T cell development in the thymus, the receptor of which hormone is expressed?
Thyroid stimulating hormone (TSH)
What is the function of TSH in T cell development?
TSH stimulates T cell development –> more differentiation
Which syndrome occurs when you have too much growth hormone?
Acromegaly
Describe the link between thymectomy and Ulcerative Colitis
After thymectomy, the percentage of patients in remission increases
What causes autoimmune disease?
Loss of tolerance
Which two categories of autoimmune diseases exist?
- Systemic
- Organ specific
Name examples of systemic autoimmune diseases (3)
- Systemic lupus erythematosus (SLE)
- Rheumatoid arthritis (RA)
- Systemic sclerosis
Name examples of organ specific autoimmune diseases (3)
- Diabetes mellitus type 1
- Autoimmune hepatitis
- Autoimmune thyroid disease
What are the most common clinical expressions of autoimmune thyroid dysfunction? (2)
- Hashimoto’s thyroiditis (HT)
- Graves’ disease
Which three structures can be found in healthy thyroid tissue?
- Thyroid follicle
- Colloid
- Follicular cells
Of what does a follicle consist?
Colloid + surrounding follicular cells
What is the function of the colloid?
What is the function of the thyroid hormone T4?
Regulates a.o. metabolism, mood, and body temperature
What is the function of the thyroid hormone T3?
Regulates metabolism, digestive tract, and bone health
How is the thyroid hormone regulated?
THR (hypothalamus) –> TSH (pituitary) –> T4 (thyroid) –> inhibits production of THR and TSH
What is the immunopathophysiology of Hashimoto?
- Massive T/B-lymphocyte and NK cell infiltrate
- Locally activated Tg-specific T-lymphocytes
- Autoantibodies to Tg and TPO
- Immune cells cause damage to thyroid tissue
Which immune cells play a role in Hashimoto? (3)
- Auto-reactive CD4+/CD8+ T cells
- Macrophages induce damage to thyrocytes
- NK cells
What is the immunopathophysiology of Graves’ disease? (4)
- Limited immune cell (T lymphocyte) infiltrate
- Locally activated TSH receptor specific T-lymphocytes
- Stimulating autoantibodies against TSHR
- Limited thyroid destruction
What is thyroglobulin (Tg)? What do you see during immunofluorescence?
Precursor protein for thyroid hormone -> thyroid follicles completely green
What is thyroid peroxidase (TPO)? What do you see during immunofluorescence?
Enzyme involved in iodination of Tg -> thyroid follicular cells light up green
To what are stimulating autoantibodies directed in GD? Causes what?
TSH-receptor (TSHR), stimulates production of thyroid hormone
How does antibody dependent cell mediated cytotoxicity work with respect to the thyroid? (4)
- Antibodies bind antigens on thyroid cells
- Fc receptors on NK cells recognize the antibodies
- Crosslinking of Fc receptors leads to NK cell activation
- Thyroid cells die by apoptosis
Hashimoto is hyper/hypo thyroid
Hypothyroid
Graves’ disease is hyper/hypothyroid
Hyperthyroid
How do you diagnose a HT patient?
- Very high levels of TPO Ab (correlate with amount of tissue damage)
- Very low TSHr Ab (esp blocking)
- T4, T3 go down
- TSH goes up
How do you diagnose a GD patient?
- Almost 100% of patients has TSHr Ab (esp stimulation)
- T4, T3 go up
- TSH goes down
A patient with HT can present with hyperthyroidism (instead of hypo), why would that be?
Destruction of the follicles –> thyroid hormone is released into the system
What are environmental risk factors for thyroid disease? (4)
- Dietary iodine intake
- Smoking
- Infection
- Stressful live events
What are susceptibility genes for GD? (2)
- HLA-DR3
- CD40
What are susceptibility genes for HT?
- CTLA-4
- PTPN22
What are the three factors of the multifactorial pathogenesis of autoimmune thyroid disease?
- Cellular interactions
- Genetic factors
- Environmental factors
How does neonatal GD come to be?
Transplacental transport of maternal IgG in the third trimester
Why is neonatal GD self limiting?
Maternal antibodies are broken down after birth
What happens in Graves’ Ophthalmopathy? (2)
- Extraocular muscle enlargement
- AND/OR orbital tissue/fat expansion
What is the immune mechanism of Graves’ Ophthalmopathy?
Orbital fat: fibroblasts that express the TSHr become activated by stimulatory autoantibodies
Result: Production of cytokines AND proliferation of fibroblasts/production of connective tissue components
Which signaling pathway is also activated in patients with Graves’ Ophthalmopathy?
Stimulatory autoantibodies against the TSHr also activate indirectly IGF-1R signaling –> promotes cell proliferation, growth and survival
Which type of bone cells are there? (4)
- Osteoclasts
- Osteoblasts
- Osteocytes
- Bone marrow cells
What is the function of osteoclasts?
Dissolve and break down old or damaged bone cells
What is the function of osteoblasts?
Form new bones and add growth to existing bone tissue
What is the function of osteocytes?
Involved in the perseverance of the bony matrix
What is the function of bone marrow cells?
BM releases blood cells into the bloodstream when they are mature and when required
Which types of bone marrow cells exist? (2)
- Mesenchymal stem cells
- Hematopoietic stem cells
Functions of the skeletal system (5)
- Support/movement
- Protection of organs
- Blood formation
- Calcium/phosphate balance
- Source of growth factors
What’s the function of the calcium/phosphate balance as main mineral reservoir?
Stores calcium phosphate and releases them according to the body’s physiological needs
Describe the differentiation of osteoblast lineage cells
Mesenchymal progenitors –> pre-osteoblast –> mature osteoblast –> osteocytes
Which cells are marked by Sox9?
All osteoblast progenitors
