When the Immune System goes wrong Flashcards by An Nakamura

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

How well did you know this?

Not at all

Perfectly

Definition of allergy

Immediate hypersensitivity, mediated by IgE, mast cells, Th2

Induced by allergen

How well did you know this?

Not at all

Perfectly

Definition of atopy

The inherited tendency to make immediate hypersensitivity responses

How well did you know this?

Not at all

Perfectly

Definition of wheal

Raised lesion

How well did you know this?

Not at all

Perfectly

Definition of flare

Surrounding redness

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Definition of autoimmunity

Loss of immunological tolerance to self components

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

Definition of immunodeficiency

When the immune system is unable to initiate an immune response

How well did you know this?

Not at all

Perfectly

Definition of iatrogenic

Caused by drugs and treatment to treat a different immunodeficient disease

How well did you know this?

Not at all

Perfectly

Definition of cancer

Forms as a result of failure of immune surveillance by Treg

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Name 4 allergy related diseases and 5 therapies used

Asthma
Hayfever
Eczema
Anaphalaxis

Antihistamines
B2 agonists
Corticosteroids
Desensitisation
Monoclonal AB vs IgE (Omalizumab)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

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