BB5MOP Week 18

Define hypersensitivity.

Immune system is overreacting to something that it does not need to react to.

How many types of hypersensitivity are there?

Four types

What is Type 1 hypersensitivity?

Allergies, where the immune system is responding to something that is harmless (innocuous antigens).

What antibody and cell are involved in Type 1 hypersensitivity?

IgE and mast cells

Describe Type 1 hypersensitivity.

1. Exposure to an allergen like pollen.

2. IgE is produced, activating the mast cells when they bind.

3. Mast cells degranulate and release histamines.

What medication is used to prevent binding and degranulation of mast cells?

Antihistamines

What are the immediate and late responses of Type 1 hypersensitivity?

1. Immediate is the degranulation of mast cells.

2. Later response is the swelling of the allergic site.

What other inflammatory molecules are going to the allergic site and what can be the consequence of this?

1. Cytokines

2. If too much go to the allergic site, anaphylaxis can occur, massive inflammatory response of the whole body.

What medication is used to prevent anaphylaxis following cytokine releasing?

Epinepherin

What is Type 2 hypersensitivity?

Antibody-mediated hypersensitivity

Describe a reaction to penicillin in relation to Type 2 hypersensitivity.

1. Penicillin binds and immobilizes onto the RBC, using a strong high energy bond in the beta-lactam.

2. Beta-lactam ring modifies the proteins in RBCs.

3. T cell activated response drives CD4 T helper cell.

4. B cells activated secreting plasma cells - specific IgE penicillin antibodies.

5. IgE binds to mast cells, degranulation and histamines - anaphylaxis because of overreacting.

Describe a reaction to blood transfusions in relation to Type 2 hypersensitivity.

1. Incorrect blood given.

2. O cannot receive A, B or AB, O does not have sugars so produces antibodies to other blood types.

Describe a reaction from mothers to their babies in relation to Type 2 hypersensitivity.

1. Mother is rhesus negative, baby is rhesus positive.

2. Initially, weak IgE molecules released - still a heathy baby.

3. Upon second pregnancy, IgG molecules released, stronger affinity - anaemic baby.

What is Type 3 hypersensitivity?

Immune complex-mediated hypersensitivity

Define Type 3 hypersensitivity.

The body reacts to soluble antigens producing an IgG antibody response, forming immune complexes deposited on blood vessel wall.

Give two examples of Type 3 hypersensitivity.

1. Lupus (SLE)

2. Serum sickness

What is Type 4 hypersensitivity?

T cell-mediated hypersensitivity

Describe Type 4 hypersensitivity.

Driven by a T cell response, producing a delayed response because T cells takes time to activate fully.

Describe a reaction to poison ivy in relation to Type 4 hypersensitivity.

1. Poison ivy broken down and presented to Langerhans cells.

2. T helper cells help recognise poison ivy antigens, releasing cytokines activating the immune system.

Describe a reaction to gluten in relation to Type 4 hypersensitivity.

1. Gluten broken down into peptides to be modified.

2. Glutamine in gluten becomes glutamic acid (Q to E), presented to APCs activating T helper cells.

3. Recruitment of more immune cells to site of infection, chronic inflammation due to cytokine releasing.

Define autoimmunity.

When own defences turn and attack the body.

Explain one way autoimmunity can happen.

Pathogens can do molecular mimicry, pathogens look like human cells causing immune system to attack human cells and not the pathogen.

Apart from molecular mimicry, explain another way autoimmunity can happen.

1. Release of sequestered antigens, hidden in cells, following mutations these antigens are released.

2. MHC class may accidently present human cell antigen alerting immune system.

Give two examples of autoimmunity.

1. Lupus (SLE)

2. Type 1 diabetes

Why do women have a higher chance of autoimmunity than men?

Females carry two X chromosomes, which carry the most genes, meaning more genes increases the chance of varying autoimmune diseases.

How does oestrogen influence autoimmunity?

Levels of oestrogen fluctuate a lot during periods and pregnancy, so can trigger autoimmune diseases.

How does pregnancy help women with rheumatoid arthritis and what is the consequence after pregnancy?

1. Theory based on increased hormonal changes that protect them from RA, leading to cortisol being the treatment for RA.

2. Pregnancy masks the symptoms of RA, so still occurs after pregnancy.

What are the three most common therapies?

1. Steroids

2. Biological therapies

3. Disease modifying drugs

Describe steroids as a common therapy method.

Reduce inflammation and suppress the immune response.

Describe disease modifying drugs as a common therapy method.

Slow down the disease by slowing down the immune cells, take longer but works better.

Describe biological therapies as a common therapy method.

Target specific molecules, fewer side effects.

Give an example of a biological therapy and explain it.

1. TNF-a (a cytokine)

2. TNF-a blocked during inflammation, slowing down disease process.

How are immune checkpoint inhibitors used as a treatment method?

Used to block checkpoint sites on immune cells, prevents cancer cells from hijacking and mutating checkpoint sites.