When the Immune System goes wrong Flashcards
Definitions of hypersensitivity
Immune response to a harmless molecule, ignored by the immune systems of the majority but initiating in some people, a response that leads to tissue damage and even death
Definition of allergy
Immediate hypersensitivity, mediated by IgE, mast cells, Th2
Induced by allergen
Definition of atopy
The inherited tendency to make immediate hypersensitivity responses
Definition of wheal
Raised lesion
Definition of flare
Surrounding redness
Definition of desensitisation
The ability to reduce the inflammatory response as a result of increased exposure to an antigen that leads to an allergic response
Definition of autoimmunity
Loss of immunological tolerance to self components
Definition of an autoimmune disease
Loss of immunological tolerance to self components associated with pathology
Accompanied by 1 or more manifestations of autoimmunity (T, B cell)
Definition of immunodeficiency
When the immune system is unable to initiate an immune response
Definition of iatrogenic
Caused by drugs and treatment to treat a different immunodeficient disease
Definition of cancer
Forms as a result of failure of immune surveillance by Treg
What is an allergy
How would you describe the genetic aspect of allergies
Immediate hypersensitivity to harmless molecules that initiates a response => tissue damage/death
Atopy affects 30-50% of population
Describe how an allergic reaction arises on a cellular level
APC presents allergens on MHC => CD4 differentiates to Th2
IL4, 5, 13 activates B cells => plasma cell, IgE class switch
IgE binds to mast cells in mucosal sites
Binding/crosslinking of allergies => mast degranulation releases histamines
Results in sneezes, wheals and flares
Name 4 allergy related diseases and 5 therapies used
Asthma
Hayfever
Eczema
Anaphalaxis
Antihistamines B2 agonists Corticosteroids Desensitisation Monoclonal AB vs IgE (Omalizumab)
What is autoimmunity
Describe the prevalence
What is the most common autoimmune condition
Describe the 2 types of autoimmune disease
What 4 diseases are more prevalent in females than males?
Loss of tolerance to self
5% develop 1 at any point in their lives
Most common => Graves thyroiditis
Varying prevalence between sexes
- Addisons
- Scleroderma
- Hypothyroidism
- Sjogrens
Organ specific/systemic
What are autoantibodies
IgG that targets self cells
What pathology is associated with the autoantibody rheumatoid factor (anti IgG) and anti citrullinated peptide
Rheumatoid arthiritis
What pathology is associated with the autoantibody anti DNA and nucleoprotein
SLE
What pathology is associated with the autoantibody antimyeloperoxidase/proteinase 3
Autoimmune vasculitis
What pathology is associated with the autoantibody anti islet cell antibodies, GAD65, insulin antibodies IA-2, ZnT8
T1D
What pathology is associated with the autoantibody anti myelin basic protein
MS
What pathology is associated with the autoantibody anti thyroid stimulating hormone receptor
Graves disease
What pathology is associated with the autoantibody anti Ach receptor
Myasthenia Gravis
What can prove that a condition is an autoimmune one
Passive transfer of disease by immune effectors (T cells. AB)
-IgG transfer to fetus in Graves and MG
Clinical responsiveness to immune suppression/reestablishment of tolerance
-RA and T1D
How does the thyroid normally function without being affected by Graves disease
TSH produced by pituitary
TSH binds to receptor on thyrocyte
Thyroxine production stimulated
Results in -ve feedback, prevents excess TSH production
How does the thyroid function when affected by Graves disease
What are the associated symptoms
Anti TSH receptor AB bind so thyroxine production is constantly stimulated
Constant stimulation, no feedback loop
Increased HR Hyperactivity Weight loss Large goitre Bulging eyes
How does the NMJ normally function when unaffected by myasthenia gravis
Neuronal stimulus leads to Ach release
Ach binds to Ach receptors => muscle contraction
How does the NMJ function when affected by myasthenia gravis
Anti Ach receptor AB binds and damages Ach receptor
When AP reaches NMJ, Ach released
Not enough receptors => poor/no muscle contraction
How are T cells targetted in the treatment of T1D
How are T cells involved in the destruction of beta cells
Monoclonal antibodies against T cell receptors administered
Insulin production will be maintained or increase
CD4 mediates inflammation
CD8 mediates beta cell killing
Treg fails to suppress inflammation
Describe how Di George Syndrome arises (primary immunodeficiencies in lymphocyte production)
What are the associated symptoms
Failed pharyngeal arch dev => abnormal thymus
- No T cells
- B cells get less T cell help => abnormal AB prod
- Heart and facial abnormalities
Describe how SCID arises (primary immunodeficiency in lymphocyte production)
How is it treated
Lack of key molecules needed for T and B cell development
- No T, B cells
- Gene therapy
Describe how chronic granulomatous disease arises (primary immunodeficiency in neutrophils)
What causes it
How is it treated
Single gene defects in reactive oxygen compound formation
Bacterial cells phagocytosed but not killed, forms inflammatory granuloma
-BM transplants and gene therapy used
Describe how hyper IgM syndrome arises (primary immunodeficieny in plasma cells)
What happens as a result
Defective CD40 ligand => B cell dev, class switch fails
- IgM is the only antibody made
- T cell response is also impaired
How does HIV affect CD4 (secondary immune deficiency)
How is HIV treated
CD4 receptor does not function, no of CD4 falls
CD8 tries to help by killing affected cells but overall Th numbers fall
Initial exposure => increased IgM, IgG and decreased p24
But as Th numbers fall,=> decreased IgM, IgG and increased p24 as antibody production not stimulated
HAART stabilises CD4 cell loss and controls viral infectiom
Can restore life expectancy
What is an iatrogenic immune deficiency and what are some examples of this
Treatment of immunity related diseases => secondary immune abnormalities
- Monoclonal anti TNFa for RA => mycobacterial infections
- Monoclonal antiIL17 for psoriasis => severe systemic fungal infections
IL17 needed for fungal infection protection
How do cancer cells affect Treg function
Cancer cell expresses PDL1, binds to PD1 on Treg
Treg cannot carry out immune surveillance
How is the immune surveillance function restored
AB to PDL1/PD1 binds and blocks signal that stops immune surveillance
Immune cell can function and cancer cell can be killed
