WK3: Hypersensitivity &

what is the definition of allergy

• it is basically an unwanted inflammatory and immune response which triggers an allergic reaction

what are the 4 types of allergy hypersensitivity

1. type i: immediate or anaphylactic hypersensitivity

2. type ii: antibody-dependent cytotoxic hypersensitivity

3. type iii: complex-mediated hypersensitivity

4. type iv: cell - mediated

list 3 predisposing genetic factors for why you could have an allergy

1. certain alleles of HLA class ii genes

2. Th2 cytokine genes

3. pro-inflammatory response genes

what are 3 environmental factors which make us prone to allergy

1. excessive hygiene

2. having fewer siblings 

3. receiving antibiotics and vaccinations as an infant

Describe the following for Type I : common name, immune system mediator, time to symptoms, it mechanism and an example

• some common names are allergy, immediate HS and IgE-medited HS

• it is mediated by the antibody IgE

• it takes less than 30min-1min for symptoms to occur

• its mechanism is the allergens bind & connect to multiple IgE antibodies which is attached to the mast cell surface triggering the releases of histamine and causing an allergic reactions

• some examples are hayfever & asthma 

Describe the following for Type II : common name, immune system mediator, time to symptoms, it mechanism and an example

• common name: direct antibody mediated cytotoxic HS

• immune system mediator: mediated by the antibody: IgG or IgM

• time to symptoms: 5-8 hours

• it mechanism : the antibody binds to cell-bound allergen and the cell is then triggered & destroyed by phagocytosis

• example: Haemolytic anaemia ( blood cells destroyed in the body)

Describe the following for Type IIII : common name, immune system mediator, time to symptoms, it mechanism and an example

• common name: immune complex mediated Hs

•  immune system mediator: is the antibody IgG or IgM

• time to symptoms: 4-6 hour

• it mechanism: the immune complex triggers activation

• an example: Arthus reaction(hard painful swelling), systemic lupus

Describe the following for Type IV : common name, immune system mediator, time to symptoms, it mechanism and an example

• common name: delayed type Hs, cell mediated HS

• immune system mediator: T-cells or Macrophages

• time to symptoms: are from 24-72 hours

• its mechanism: the t-cells produce IFN-Y & other cytokines which leads to macrophages hyperactivation

• an example: poison ivy, lesions of Tb & leprosy

what happens when an allergen cross-links IgE on mast cells

• it activates mast cells which causes degranulation & the release of histamine leading to allergic reaction

what is an anaphylactic shock

• anaphylaxis is a serve whole body allergic reaction, when exposed to a substance like a bee sting, the person immune system become sensitised to the allergen causing a reaction to occur

list 3 common causes of allergens

1. insect bite

2. food allergies

3. drug allergies

4. pollen - but rarely causes anaphylaxis

Anaphylaxis occurs infrequently but it is very life threatening

how can anaphylactic shock be treated? suggest 3 ways?

1, an epinephrine should be administered by injection, this open up the airways and increase BP without constricting blood vessels

2. another is IV fluids and medication to support the heart and circulatory system

3. antihistamines and corticosteroids may be given to further reduce the symptoms

suggest 4 complication of anaphylactic shock

1. shock

2. cardiac arrest

3. airway obstruction

4. respiratory arrest

describe Type II hypersensitivity

• an example is blood transfusion with the wrong type of blood

• it is dependent on antibodies

• IgG or IgM membrane associated antigens

• target cells become coated with antibodies - leading to cell destruction by phagocytosis or Complement dependent cytotoxicity

describe the type iii hypersensitivity

• they have immune complexes which are not cleared from the blood

• they are often lodged in narrow channels in the body, provoking an immune response which damages the surrounding cells

• many type iii reaction are complication of infection with pathogen like malaria or hepatitis

• and example is localised type iii HS in patient which are rare like Arthurs reaction

• systemic type iii HS is a part of the body that involves trapping large immune complexes: joint, capillaries and renal glomeruli

describe the the type IV

• type iv is also called delayed type hypersensitivity

• examples contact dermatitis

• it has a delayed reaction from 24-48 hours

• It is T cell mediates and require CD4+ and CD8+

• APC takes the antigen to present to the T cells

what are the effects of histamine on type i allergic repsonse?

• some effects include hay fever, asthma, death

• the triple response: dull red spot, enlargde red halo

• elevation of the skin

describe the reduction of the effects of released histamine

1. physiologic antagonist - epinephrine has smooth muscle action opposite to histamine , but they act on different receptors - these are used in conditions of massive release of histamine

2. histamine release inhibitors - reduce immunologic release of histamine from mast cells , a mast cell stabiliser includes cromolyn and nedocromil & beta 2 agonist

3. histamine receptor antagonist

what is the histamine 1 antagonist first generation

• it is sedating and a lipophilic compound ready to cross the BBB

what is the second generation histamine 1 antagonist

• it is non-sedating and poorly penetrates the BBB

describe the pharmacokinetic of the first generation agents

• they are rapidly absorbed from the GIT, widely disturbed and cross the BBB

• they can be metabolised by cytochrome P450 and then metabolites are active then excreted via the kidney

• its DOA is 4-6 hours

describe the pharmacokinetic of the second generation

• rapidly absorbed from the GUT widely distributed, but does not cross the BBB as it less lipid soluble

how is the drug cetirizine eliminated

through urine

how is the drug fexofenadine eliminated via

bile

suggest 2 effects not related to blockade of H1 receptors

1. anticholinergic Effects

2. the central nervous system

list 6 1st generation drugs

1. carbinoxamine

2. diphenhydramine

3. dimenhydrinate

4. cyclizine

5. chlorpheniramine

6. promethazine

name 3 second generation drugs

1. fexofenadine

2. loratadine

3. cetirizine

what is cromolyn and nedocromoyln

• it is given as a powder by inhalation for prophylaxis against bronchial asthma and allergic rhinitis

• its inhibits histamine release by inhibiting chloride channels on mast cells

what is the immunogen and tolerogen

the immunogen is a substance which is capable of eliciting a immune response whereas, tolerogen are antigen which induce tolerance rather than thmmune system