Function of the immune system?
How does it do this?
To identify and eliminate harmful micro-organisms
It recognises ‘self’ and ‘non self’ and also identifies danger signals Eg: Inflammation
Describe what happens (briefly) when a pathogen enters?
Pathogen Entry
Immediate Innate Response: Complement, Mast Cells, Inflammation, Macrophages
Early Innate Response: Phagocytes, Inflammation
Late Response: Adaptive/Acquired Immune Response
Describe what the innate immune system is like?
Rapid and quick response
‘Fire fighting’ - it isn’t a specific response
Targets groups of pathogens
Describe what the acquired immune system is like?
Slower response
Specific, targeted response to the antigen
Can respond to many microbial structures
Describe memory in the immune system
Innate has no memory
Adaptive has memory
Describe the general innate immune system components?
Physical Barrier
Commensal Bacteria
Chemicals
Cells
Describe what parts of the general innate immune system are different in the eye?
No physical skin barrier
Very few commensal bacteria
How does the eye innate immune system compensate?
Blink Reflex
Limiting Exposure/Size
Physical and chemical properties of eye surface (tears)
Describe tears in terms of physical?
Function as a physical barrier
Every time we blink, they wash over the eye and form a tear film
Flush out any trapped particles/bugs
Describe the tear film?
Protective layer of tears
Composed of three layers:
- Lipid, Oil - Seals eye to prevent tear evaporation
- Aqueous, Water – Flushes out particles
- Mucous - Allows watery layer to spread evenly
Describe tears in terms of chemicals?
Contain many chemicals important for protections:
- Lysozymes
- Lactoferrin/Transferrin
- Complement
- Tear Lipids
- Secretory IgA
Describe tears in forms of cells?
Contain many cells important for protection
- Neutrophils
- Macrophages
- Conjunctival Mast Cells
The innate immune system is composed of a XXXXX barrier, commensal organisms, XXXX and XXXXX. The eye has no skin to form a physical barrier and no commensal organisms however it is protected by XXXX and XXXXX of the eye.
The innate immune system is composed of a physical barrier, commensal organisms, cells and chemicals. The eye has no skin to form a physical barrier and no commensal organisms however it is protected by tears and blinking of the eye.
Tears can provide a XXXX against micro-organisms by forming a XXXX layer tear film. Tears also contain chemicals which can help to protect the eye. Tears can also attract cells such as XXXXXX, macrophages and conjuctival XXX cells to help protect the eye.
Tears can provide a physical barrier against micro-organisms by forming a three layer tear film. Tears also contain chemicals which can help to protect the eye. Tears can also attract cells such as neutrophils, macrophages and conjuctival mast cells to help protect the eye.
What two things are required for the acquired immune system?
Antigen presenting cells
Lymphatic drainage to node
Describe the cornea?
The cornea is avascular and there is no lymphatic drainage or lymphoid tissue associated with it. It is exposed and needs immune defence however it is very hard for the immune system to protect the cornea
Where does most of the cornea immune defence come from?
Conjunctiva
Describe the conjunctiva?
This is vascular, has lymphoid tissue associated and has lymphatic drainage. Does most of the immune defence for the eye. Produces inflammatory mediators and contains macrophages (used in both acquired and innate)
Describe the choroid, vitreous and retina
This is where the blood barrier occurs
However, lack of antigen presenting cells
Poor immune defence
What is immune privilege?
This is the ability to tolerate antigen presence without eliciting an inflammatory immune response
Which areas of the body have immune privilege?
Brain
Genitals
Eyes
Placenta/Foetus
Describe ocular immune privilege?
This is due to the unique blood barrier and the lack of lymphatic drainage. There are many immunosuppressive molecules that prevent immune response. Foreign bodies in the eye lead to systemic tolerance - Anterior Chamber Associated Immune Deviation (ACAID)
Why does ocular immune privilege occur?
A small amount of inflammation in the eye can cause damage therefore preventing inflammation is a good idea
What is sympathetic ophthalmia?
This is granulomatous uveitis (inflammation) of both eyes caused by trauma to just one eye
Caused by trauma and surgery
Describe sympathetic ophthalmia pathophysiology?
Trauma or surgery to one eye causes antigens to introduced. This causes immune response and production of CD4+ helper cells and CD8+ cytotoxic cells. Causes damage to both eyes and can lead to blindness
How can you tell which was the initially damaged eye in sympathetic ophthalmia?
History
Upon examination, there is no difference
The immune system can be defective. It can be either…
Hyperactive
Absent
Describe a normal immune system
Protects from dangerous pathogens
Ignored innocuous stimuli
Tolerance to self
Rejection of transplanted tissue
Describe an absent immune system
Recurrent, severe infections Ignored innocuous stimuli Tolerance to self Acceptance of transplanted tissue Cancer
Describe a hyperactive immune system
Protects from dangerous pathogens
Reaction to innocuous stimuli
Reaction to self
Rejection of transplanted tissue
What is a hypersensitivity reaction?
This is an immune response that causes bystander damage - a normal immune response that has been exaggerated
Basis for many diseases - allergy and autoimmune diseases
Name the four types of hypersensitivity reactions
Type 1 = Immediate Hypersensitivity
Type 2 = Direct Cell Killing
Type 3 = Immune Complex Mediated
Type 4 = Delayed
Describe Type 1 Hypersensitivity reactions?
Antigen presents
B and T cells produce specific IgE antibodies
Allergen is cleared
Residual IgE binds to Fc region receptors on mast cells
Allergen is re-encounter
Binds to mast cell
Causes degranulation and release of histamine, tryptase, cytokines and inflammatory mediators
Give an example of a type 1 hypersensitivity reaction?
Acute Allergic Conjunctivitis - red, swollen, itchy eyes from contact with an allergen e.g.: Pollen
What is Chemosis?
Swelling of conjunctiva, sign of eye irritation
Describe type 2 hypersensitivity reactions?
This is antibody mediated direct cell killing
Antibodies produced by B and T cells
Bind to the antigens
This binding causes complement activation and phagocytosis
Killed by macrophages and natural killer cells or complement
Give an example of type 2 hypersensitivity reactions?
Ocular Cicatricial Pemphigoid
Autoimmune disease that causes destruction of the cornea and can lead to blindness
Describe type 3 hypersensitivity reactions?
Immune Complex Mediated
The antigen and antibody are both free circulating
Bind together to form immune complexes
Small immune complexes become deposited in vessels where they become stuck
Sets up an inflammatory process - activate complement and recruit macrophages and neutrophils
Give an example of a type 3 hypersensitivity reaction?
Autoimmune corneal melting
Describe type 4 hypersensitivity reactions?
This is delayed type hypersensitivity
Mediated by T cells
There is initial exposure to the antigen which is then cleared by the immune system
Specific TH1 antibodies to that antigen are produced
When antigen re-appears/if exposure continues, TH1 cells produce inflammatory mediators and cytokines
Inflammation
Give an example of a type 4 hypersensitivity reaction?
Rejection of a corneal graft
What are the three pathways for complement? (1st Year Immunology Revision)
Classical
Alternative
Lectin
Describe the classical pathway for Complement?
C1, C2 and C4
Antibody/Antigen complex binds to these
Converted into C3
Describe the four functions of Complement?
Hole Puncher (Membrane attack complex - direct cell killing)
Land Rover (Increased permeability of blood vessels, allow increased cell recruitment to inflamed area)
Ketchup (Opsonisation - complement can coat micro-organisms to make them look ‘tastier’ to phagocytes)
Soluble (Complement trigged by immune complexes - by dissolving these immune complexes then complement has a negative feedback loop)
Describe what happens when you give someone with ‘type A’ blood a transfusion of ‘Type B’ blood
Type A person has anti-B antibodies
When given type B blood, the antibodies bind to the type B red blood cells
Causes complement activation and inflammatory cascade
Lysis of donated blood cells
Profound inflammatory response
Can be fatal
Describe how acute hypersensitivity pneumonitis occurs (Pigeon Fancier’s Lung)
Allergen is inhaled Immune complexes are formed Deposited in alveoli Causes inflammation and cell recruitment Causes wheezing, malaise and breathlessness as alveoli are disrupted by inflammation