IAI - when immune system goes wrong Flashcards
What is immediate hypersensitivity?
Allergy
Mediated by IgE, mast cells and Th2 responses
What is atopy?
an inherited tendency to make immediate hypersensitivity responses
What is the immediate hypersensitivity response due to?
Due to mast cell
degranulation and histamine release and when it happens in the skin there is a wheal and flare.
- Wheal = raised lesion
- Flare = surrounding redness
What is the Th2 response to allergy?
What are serum autoantibodies?
- Usually IgG class
- Important diagnostic tools
- Useful for monitoring disease activity
- Useful for predicting future disease
- May be pathogenic (ie cause disease)
Describe Graves’ disease.
It is an autoimmune thyroid disease.
How is homeostasis of the thyroid gland and production of thyroxine is maintained in a healthy person?
- Production of thyroxine by the thyroid gland is regulated by thyroid stimulating hormone (TSH) produced by pituitary gland.
- Binding of TSH to the TSH receptor stimulates the production of thyroxine.
- Negative feedback by throxine prevents excess TSH production by the pituitary gland.
What occurs in Graves’ disease causing homeostasis of the thyroid gland to be unregulated?
- An autoantibody is produced which binds to the anti-TSH receptor on the thyrocyte and maintains it on the on position.
- The thyroid gland keeps making thyroxine in a completely unregulated way which leads to the symptoms of hyperthyroidism.
- As a result there is constant stimulation of the thyroid and pituitary with no feedback loop.
- Patients can therefore experience a fast heartbeat, hyperactivity, weight loss, bulging eyes and a neck goitre.
What is myasthenia gravis?
Myasthenia gravis is impaired connection across the neuromuscular junction. This is due to patients developing autoantibodies to the acetylcholine receptor. These lead to damage and a number of receptors on the muscle side are reduced. = muscular weakness and fatigue.
What occurs in the last trimester of pregnancy?
Maternal IgG is transported across the placenta to protect the baby during the first weeks of life until the baby’s own antibody response develops.
How does neonatal Graves’ disease occur?
Mother with Grave’s disease has IgG autoantibodies to thyroid stimulating hormone (TSH) receptor.
cross placental transfer of igG in the last trimester
How does type 1 diabetes occur?
Type 1 diabetes is also an autoimmune disease - it is a progressive loss of the insulin producing beta cells of the pancreas resulting in failure to regulate blood sugar levels.
what mediates type 1 diabetes
type 1 diabetes is T cell mediated.
How is type 1 diabetes T cell mediated?
- CD8 T cell mediated killing of Beta cells
- CD4 T cell mediated inflammation
- Failure of Treg to suppress
What categories are immunodeficiency split into?
- PRIMARY = inherited defect = rare
- SECONDARY = acquired defect = common
What is the Di George Syndrome and how does it occur?
NO T CELLS
the thymus doesn’t form and so there are no T cells in the blood or in the lymphatics
associated with abnormalities of the heart and facial features in addition to immunodeficiency.
What is SCID and how does it occur?
NO B CELLS
The pathways that lead to B cells and T cells can be disrupted, often due to the lack of key molecules such as cytokines or surface receptors that are required for the immune development of B lymphocytes and T lymphocytes.
As a result children will lack both in their early months of life. The consequences are Severe Combined Immune Deficiency or SCID.
What is chronic granulomatous disease?
NO NEUTROPHILS
- In this disease the neutrophils can surround this area of bacterial infection but they can’t get rid of it because they can’t kill the bacterial cells themselves - forming a large inflammatory focus called a granuloma.
- This diagnosis of this disease is more likely to occur early in life as children are exposed to their first bacterial infection.
What is hypergammaglobulinemia (hyper IgM syndrome)?
NO PLASMA CELLS
In the absence of CD4 T ligand, productive B-lymphocyte responses are not made, plasma cells do not develop and the only antibody that the children can make is IgM
As a consequence of not being able to interact properly with the B-lymphocyte, T-lymphocyte responses are also impaired in CD4 T ligand deficiency. This can be known as either hyper IgM syndrome or CD4 T ligand deficiency.
What is the most common secondary immune deficiency?
AIDS caused by human immunodeficiency virus, HIV.
How does AIDS occur?
HIV infects CD4 T cells through the CD4 receptor itself.
CD4 T-cells decline
CD8 T-cells wipe out CD4 T-cells
what theraputic approach helps HIV/ AIDS
Highly Active Antiretroviral Therapy (HAART).
early on in HIV/AIDS what protein is detected in the serum
protein p24
What is iatrogenic immune deficiency?
Increasing numbers of patients being treated with immune based therapies.
These may cause highly focused secondary immune abnormalities.
what are examples of iatrogenic immune deficiency?
- Monoclonal anti-TNF-α therapy for rheumatoid arthritis results
in unusual opportunistic infections including mycobacterial
infections. - Monocloncal anti-IL-17 therapy for infammatory diseases such as psoriasis can give rise to severe systemic fungal infections; telling us that IL-17 is a key component of protection from fungi
What is cancer?
The failure of immune surveillance CD4+ Treg
PD-1 is present on effector cells and PD-L1 can be present on cancer cells.
what major pathway is immune surveillance controlled by?
PD-1 and PD-L1 interaction (programmed death - 1 and programmed death ligand 1).
what are examples of primary diseases
- Di George Syndrome
- SCID
- chronic granulomatous disease
- hypergammaglobulinemia - hyper IGM syndrome
whats an example of a secondary disease
HIV
what is post transplant lymphoproliferative disease PTLD:
- disease in reaction to transplants
- healthy B cells infected with Epstein Barr Virus EBV
- EBV normally controlled by cytotoxic T cells (CD8T)
- T cells suppressed by drugs preventing rejections of transplant
- cytotoxic cells cannot control infected B cells = malignant transformation = form B cell lymphoma
do keats quiz on when immune system goes wrong
https://keats.kcl.ac.uk/mod/lesson/view.php?id=6620827
do keats quiz on self check for immunology
https://keats.kcl.ac.uk/mod/quiz/view.php?id=6620854
what are common therapies to allergies/immediate hypersensitivities?
- Anti-histamines
- Beta2-adrenoceptor agonist
- Corticosteroids
what are rare therapies to allergies/immediate hypersensitivities?
- Desensitization
- Monoclonal antibody - against IgE (Omalizumab)
What is immunological self tolerance?
Controlled failure to respond to self despite having the capability to do so
What is autoimmunity?
Loss of immunological tolerance to self components
Transfer of IgG antibodies to the fetus in utero only occurs in autoimmune diseases, and this proves that they are immune mediated conditions.
true or false
Transfer of IgG antibodies to the fetus in utero is a feature of pregnancy to that provides the baby with immune protection immediately after birth. The transfer of antibodies to autoantigens in mothers with autoantibody mediated diseases such as Graves’ diseases and myasthenia gravis results in disease in babies that is reversible by plasmapheresis.
Secondary immune deficiencies can result from treatment with therapies to cure autoimmune diseases.
true or false
Immunosuppression can resolve autoimmunity but leave the patients immunodeficient and susceptible to infection.
