Immunology

Question 1

What are the solutions the bodies immune system has developed due to the fact they eye has no physical barrier and not really any commensal bacteria ?

Answer 1

1. Blink reflex
2. Physical and chemical properties of eye surface
3. Limit exposure/size

Question 2

How does the blink reflex and physical properties of the eye help protect it ?

Answer 2

TEARS – PHYSICAL and blink reflex

• Help flush things out the eye
• Also provide a mucous layer which helps prevent things sticking onto the eye

Question 3

What are some of the chemical properties which help protect the eye?

Answer 3

• Lysozyme: v. gram –ve bacteria, fungi (destroy bacteria cell wall)
• Lactoferrin and transferrin: v. gram +ve bacteria
• Tear lipids: antibacterial to cell membranes/scavenger of bacterial products
• Angiogenin: antimicrobial effect within tear film
• Secretory IgA: prevents attachment
• Complement
• IL-6, IL-8, MIP: antimicrobial molecules that recruit leucocytes

Question 4

What the the main immune cells in the eye ?

Answer 4

• Neutrophils
• Macrophages
• Conjunctival mast cells

Question 5

What are the 3 main requirements of the adaptive immune system ?

Answer 5

1. Antigen presenting cells (APC = dendritic cells, B cells, macrophages)
2. Lymphatic drainage to lymph node
3. Variety of effector cells (incl. CD4+ T cells, CD8+ T cells, B cells)

Question 6

What is the main APC for the external eye and where are they mainly found ?

Answer 6

• Langerhans Cells (type of macrophage)
• Found mainly at the corneo-scleral limbus (junction between the cornea and sclera)

Question 7

What is the only part of the eye with lymphatic drainage ?

Answer 7

The conjunctiva

Question 8

Define what is meant by immune privilege

Answer 8

It is where a site is able to tolerate the introduction of antigens without eliciting an inflammatory immune response

Question 9

What areas in the eye have immune privilege ?

Answer 9

• Cornea
• Anterior chamber
• Lens
• Vitreous cavity
• Subretinal space

Question 10

What are some of the factors which contribute to immune privilege ?

Answer 10

• Blood-tissue barrier and a lack of direct lymphatic drainage
• Ocular microenvironment is rich in immunosuppressive molecules and inhibitory cell surface molecules that influence the reactivity of immune cells
• Anterior chamber-associated immune deviation (ACAID)

Question 11

What does anterior chamber associated immune deviation do ?

Answer 11

Protects the eye from collateral damage by suppressing a future potentially damaging response to infection.

Through:

• Generation of primed CD4+ T and B cells that produce non-complement-fixing antibodies
• Inhibition of delayed-type hypersensitivity (CD4+ Th1) and B cells that secrete complement-fixing antibodies (inhibition of a cell-mediated immune response)

Question 12

What is sympathetic ophthalmia ?

Answer 12

Development of an autoimmune reaction to ocular antigens: exposed during a traumatic or surgical event

Question 13

Describe the pathogenesis of sympathetic ophthalmia

Answer 13

1. Initialy exposed to intraocular antigens
2. Followed by Initial wave of infiltrative cells composed of CD4+ helper T cells in both eyes
3. Then followed by a secondary wave of CD8+ cytotoxic T cells

Question 14

What are some of the conditions which can occur due to problems with the immune system ?

Answer 14

• Recurrent infections
• Inadvertent injury to normal host tissues
• Allergy
• Hypersensitivity reactions
• Autoimmune disease
• Cancer
• Transplant/graft rejection

Question 15

What are the main regions on the antibiody and mast cell which interact with each other ?

Answer 15

You have the Fc receptor on the mast cell which beinds to the Fc region on the antibody

The arms of the antibody are the antigen specific regions

Question 16

Describe the process of how Type I hypersensitivity occurs

Answer 16

1. On encounter with allergen, B cells produce antigen-specific IgE antibody
2. Allergen is cleared
3. Residual IgE antibodies bind to circulating mast cells
4. Then on re-encouter with allergen the primed mast cells release vasoactive mediators (type I hypersensitivity reaction)

Question 17

Give an example of a type I hypersensitivity reaction affecting the eye ?

Answer 17

Allergic conjunctivitis - eye appears very watery and puffy

Question 18

What are the cells which are involved in Type II hypersensitivity reactions ?

Answer 18

• Macrophages/natural killer (NK) cells
• Complement (membrane attack complex)

Known as the antibody mediated cytotoxicity (direct-cell killing)

Question 19

Give an example of a type II hypersensitivity reaction affecting the eye

Answer 19

Ocular cicatricial pemphigoid - Type of autoimmune conjunctivitis, blistering and scarring of conjunctiva

Question 20

Describe type III hypersensitivity reactions

Answer 20

Immune complex mediated:

1. Excess antigen present
2. Antibodies then bind to the antigens forming immune complexes of varying sizes
3. Large immune complexes can be cleared but smaller complexes cannot be cleared so easily
4. This results in the smaller immune complexes depositing intosmall blood vessels, joints, and glomeruli, causing symptoms
5. The reaction can take hours, days, or even weeks to develop

Question 21

Give an example of an type III hypersensitivity reaction

Answer 21

Autoimmune corneal melting

Question 22

Describe type IV hypersensitvity

Answer 22

Delayed type hypersensitivity often called cell-mediated cytotoxicity

1. CD4+ helper T cells recognize antigen in a complex with MHC II major on the surface of antigen-presenting cells.
2. CD4+ T cells secrete IL-2 and interferon gamma, inducing the further release of other Th1 cytokines, thus mediating the immune response.
3. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

Question 23

Give an example of type IV hypersensitivty reactions in the eye

Answer 23

Corneal graft rejection