Lecture 20: Allergy

Question 1

Give the speed & type of response from a type 1 hypersensitivity (1 area)

Answer 1

Atopic allergy, (IgE mediated) and response is immediate

Question 2

Give the speed & type of response from a type 2 hypersensitivity

Answer 2

Complement mediated- it is medium

Question 3

What is type 3 and type 4 hypersensitivity

Answer 3

Serum sickness - medium and 
Delayed Type (DTH) slow

Question 4

What are the common triggers for Type 1 atopic allergy

Answer 4

Pollen grain - rhinitis, Dust mite

Peanuts & Bee venom- anaphylaxis

Question 5

What is anaphylaxis

Answer 5

inflammation is systemic where oedema occurs at multiple sites that are distant from the original site of allergen challenge. Eg. Lips, throat, eyes,, airway, gut.

Question 6

What are 3 common allergic responses and where are they found

Answer 6

Urticaria or hives - caused by histamine release and Oedema or swelling caused by leakage of fluid in intercellular space in skin.
Asthma occurs in bronchial tubes which inflame.

Question 7

What causes Type 1 allegergic response

Answer 7

When first exposed to allergen, the body mounts an inappropriate B cell response that produces IgE. When next challenged, this this allergen cross links pre-sensitised IgE coated mast cells which degranulate releasing chemicals that induce inflammatory response

Question 8

What are mast cells & their features that relate them to Atopic allergy. Where are they located

Answer 8

Mast cells are resident in skin/mucosa of skin and are designed to destroy large multicellular organisms.
They have Fc epsilon repceptor that has exceptionally high affinity toward IgE bound to its antigen.

Question 9

When do you do you develop the IgE response to an allergen that sensitises mast cells in the skin?

Answer 9

Early in life after birth but can also result from mother’s genetic linkage.

Question 10

What are the chemicals released by the degranulation of Mast cell

Answer 10

Powerful inflammatory mediators including Histamine, leukotriences, prostoglandins, Free radicals and Substance P.

Question 11

What is the effect these inflammatory mediators- mostly triggered by vasoactive amine: Histamine

Answer 11

Smooth muscle/ blood vessels constrict. Mucous gland=more mucous= oedema , Platelets =clotting , Sensory nerve endings= pain, and Eosinophils migrate to the site

Question 12

How does the initial inappropriate B cell response happen

Answer 12

immature B cell in the lymph node has the allergen that has triggered its B cell receptor. It then recruits a Th1 or Th2 helper CD4-Tcell. helper T cell produces cytokines (IL-4) that turn the B cell from IgM to IgE instead of IgG. This makes memory cells and plasma cells that are producing IgE

Question 13

What is the basic mechanism behind Type 2 sensitivity for Rhesus

Answer 13

An antibody in new born baby recognises the protein in the basement membrane of RBCs. Complement is deposited there. Neutrophil Fc receptor and complement receptor bind and then there is frustrated phagocytosis which causes RBCS to lyse and therefore haemolytic anaemia

Question 14

What is the main cause for Type 2 sensitivity in Rhesus (RHD)

Answer 14

Rhesus factor is a carbohydrate on the surface of RBCs- antigen. The mother is RHD negative while the baby is RHD positive. Blood mixing causes the mother to produce antibodies. Which pass over the placenta for the second baby.

Question 15

How is Rhesus treated in mothers

Answer 15

She receives an antibody that is anti RHD that kills any RBCs from the baby that get into her blood stopping her own cells from making antibodies

Question 16

What are the two treatments of allergies

Answer 16

Treatment by desensitisation and Monoclonal antibodies

Question 17

Describe treatment of allergy by desensitisation

Answer 17

Increase the conc of the allergen in the blood to help stimulate B cells to produce high affinity IgG that competes with IgE. As IgG has higher concentration it is more likely to bind before IgE preventing the type 1 response

Question 18

What is the success rate of desensitisation

Answer 18

50%

Question 19

What was the study investigating that caused monoclonal antibodies made

Answer 19

Kohler and Milstein wanted to investigate what somatic mutations occuring in the region coding for CD1,2,3 antigen binding sites were occuring in B cells after they immunised mice

Question 20

Give an example of clinical use of Monoclonal antibody

Answer 20

the antibody can isolate CD34 haemopoetic stem cell for bone marrow transplant

Question 21

how is the monoclonal antibody made

Answer 21

Mouse is immunised using the specific antigen and boosted to get a strong IgG response. Then 1 B cells producing these antibodies is taken out of spleen and fused with mouse myeloma line (immortalised nonantibody producing B cell) using PEG. This mix is called hybridoma. And this is tested to see if it is producing high specificity, high affinity antibodies by adding the antigen.

Question 22

What are the pros of Monoclonal antibodies as therapeutic agents

Answer 22

highly specific for the intended target so no off target effects. Can be tailormade with just the right affinity. humanised so can stay in blood for months, no adverse reactions or toxicity to antibody - human.
Can be modified to be bi specific for greater potency- different binding sites on same.

Question 23

What are the cons of Monoclonal antibodies as therapeutic agents

Answer 23

Expensive to develop and make commercially

Side effects of their function can be serious as its driving a process that could have unintended affects.