Immunology Flashcards
via what 2 methods can the immune system eliminate harmful micororganisms?
distinguish self from non self
identify danger signals (e.g inflammation)
what is innate immunity?
first line
physical barrier, commensal bacteria, chemical agents
what is adaptive immunity?
acquired specific learned transferable tolerance
when do the innate and adaptive immune system kick in after pathogen exposure?
immediate innate response = 0-4 hrs (complement, mast cells, macrophages, inflammation)
early innate response = 4-96 hrs (recruitement/activation of phagocytes, inflammation)
late - adaptive response = >96 hrs (immune response)
how do innate and adaptive immunity differ in terms of targeted pathogens and memory?
innate targets groups of pathogens and responds to only a limited number of microbial structures
adaptive targets specific pathogens and can respond to a huge array of different microbial structures
only adaptive has memory
are innate and adaptive immunity distinct?
no
they work together (synergistic)
describe innate imunity in the eye
no physical barrier (no skin)
not many commensal bacteria
does have chemical agents
does have protective cells
how are the limitations of innate immunity in the eye (lack of physical barrier etc) overcome?
blink reflex
limit exposure/size
physical and chemical properties of eye surface
what physical properties of the eye provide innate immunity?
tears
flushing of the eye
mucous layer = anti-adhesive
what chemical properties of the eye provide innate immunity?
tears (chemicals in tears) lysozyme (destroy fungal and gram -ve cell wall) lactoferrin and transferrin (gram +ve) tear lipids (antibacterial to cell membrane/bacterial products) angiogenin (antimicrobial effect) secretory IgA (prevents attachment) complement IL-6, IL-8, MIP (recruit leucocytes)
what immune cells in the eye provide innate immunity?
tears (immune cells in tears)
neutrophils (attracted by chemotaxis and release free radicals and enzymes)
macrophages (phagocytosis of damaged cells and help trigger adaptive immune system)
conjunctival mast cells (vasoactive mediators)
adaptive immunity in the eye requires what 3 things?
antigen presenting cells (dendritic, B cells, macrophages)
lymphatic drainage
variety of effector cells (CD4, CD8, B cells)
what is the principle antigen presenting cell in the external eye and describe its features
Langerhans cells rich in class II MHC molecules
where are Langerhans cells mainly found in the eye?
abundant at corneo-scleral limbus
less in peripheral cornea
absent in central 1/3rd of cornea
what is the only part of the eye with lymphatic drainage?
conjucntiva
what is the conjunctiva?
specialised endothelial venules for regulated migration of lymphoid cells
what is present in the conjucntiva?
diffuse lymphoid populations (CD4 and CD8 T cells, IgA secreting plasma cells)
dendritic cells
mucosa associated lymphoid tissue (MALT)
commensal bacteria
what is present in the MALT in the conjunctiva?
macrophages, Langerhans and mast cells frequent the MALT
neutrophils/eosinophils only there if recruited
what is the cornea and sclera?
tough collagen coat of the eye
what is present within the cornea and sclera?
avascular no lymphatics or lymphoid tissue relative lack of APCs Langerhans only in peripheral cornea downregulated immune environment
describe the components of the lacrimal gland
more plasma cells (IgA) and CD8 cells compared to conjunctiva
T cells in small groups around intralobar ducts
resting lymphoid cells very rarely observed
what is present in the lacrimal drainage system?
diffuse lymphoid tissue and follicles in mucosa (MALT)
describe the features of the vitreous, choroid and retina
blood -ocular barrier
relative lack of APCs
downregulated immune environment
describe the concept of immune privilege
certain sites of the human body have the ability to tolerate the introduction of antigens without eliciting an inflammatory response
name 4 areas of the body which display immune privilege
brain/CNS
testes
placenta/foetus
eyes
what sites in the eye display immune privilege (5)?
cornea anterior chamber lens vitreous cavity subretinal space
name 3 immune privilege mechanisms in the eye
unique anatomical features of a 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 deactivation (ACAID)
what is ACAID and what does it do?
“anterior chamber associated immune deviation”
systemic form of tolerance to foreign antigen (peripheral tolerance to ocular antigens)
active mechanisms downregulate the immune response within the eye and protect the eye and visual axis from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection
what are the immunological hallmarks of ACAID?
generation of primed CD4 T and B cells the 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 response)
what are the 3 principles which establish ocular immune privilege?
separation (immunological ignorance)
inhibition (development of an intraocular immunosuppressive microenvironment)
regulation (peripheral tolerance to ocular antigens)
how does separation achieve immune privilege?
corneal cells have reduced expression of MHC class I molecules and do not express MHC class II molecules normal cornea lacks blood and lymphatic vessels
how does inhibition establish immune privilege?
local factors within the eye inhibit components of the immune response to reinforce the protection provided by immune privilege
how does regulation achieve immune privilege?
ACAID
what is sympathetic opthalmia?
rare, bilateral granulomatous uveitis due to trauma (more common) or surgery (less common) to one eye
what causes sympathetic opthalmia?
secondary to development of an autoimmune reaction to ocular antigens: exposed during the traumatic or surgical event
related to the physical and immune isolation of the eye from the systemic immune system (disadvantage of immune privilege)
this means that immune response occurs at elevated rates
what cells are involved in sympathetic opthalmia?
primary mediator = T cells
initial wave = CD4 T cells
later wave = CD8 T cells
how does each eye differ in sympathetic opthalmia?
injured eye = exciting eye
fellow eye = sympathising eye
clinically both eyes appear the same, can only tell which one is exciting eye by history
how does sympathetic opthalmia occur?
trauma to one eye results in release of sequestered intraocular protein antigens
released intraocular antigen is carried to lymph node and activated T cells
effector T cells return via bloodstream and encounters antigen in both eyes
name 6 autoimmune diseases of the eye
autoimmune uveoretinitis (inflammation of uvea and retina)
Dalen-Fuchs nodule (epithelial clusters in retinal layers)
keratoconjunctivitis sicca (dry eyes)
lens induced uveitis (reaction due to release of lens products)
retina autoantibodies (common inretinopathy associated with cancer/infection/degenerative disease)
sympathetic opthalmia (bilateral granulomatous uveitis)
what is the role of mast cells in allergic reactions (type 1)?
express receptors for Fc region of IgE antibody on their surface
on encounter with allergen, B cells produce antigen-specific IgE antibody and allergen is cleared
what happens after allergen in cleared in a type 1 response?
allergen is cleared
residual IgE antibodies bind to circulating mast cells via Fc receptors
no great consequence until allergen is re-encountered
what happens when the allergen is re-encountered in type 1 response?
allergen binds to IgE coated mast cells and disrupts cell membrane
release of vasoactive mediators (histamine, tryptase etc)
also increased cytokines and leukotriene transcription
give an example of a type 1 reaction in the eye
acute allergic conjunctivitis (chemosis)
via what 2 methods are cells killed in a type 2 response?
macrophages/natural killer (NK) cells
complement (membrane attack complex)
give an example of a type 2 response in the eye
ocular cicatricial pemphigoid
- causes blistering and scarring of the conjunctiva
how may ocular cicatricial pemphigoid be managed?
steroids
- dampens down immune response
what happens in the early stage of type 3 response?
early stage = little antibody and lots of antigen, small immune complexes form that do not fix complement and are not cleared from circulation
what happens in the intermediate stage of type 3 response?
comparable amounts of antibody and antigen
large immune complexes are formed which fix complement and are cleared form circulation
what happens in late stage of type 3 response?
large amounts of antibody and little antigen
medium-sized immune complexes form that fix complement and are cleared from circulation
give an example of type 3 response in the eye?
autoimmune corneal melting
what cells are involved in type 4 response?
T helper cells activated by intracellular pathogens
clonal expansion
when re-exposed, macrophages attracted
leads to exaggerated immune response
what are the 2 phases in type 4 hypersensitivity?
sensitisation phase
effector phase
give an example of type 4 hypersensitivity in the eye
corneal graft rejection
what factors may help in maintaining immune privilege in a corneal transplant?
reduced/impaired expression of MHC I and II in corneal cells
cornea lacks blood and lymph vessels
central cornea is deficient in Langerhans cells
secretion of molecules with immunosuppressive properties
expression of surface molecules that inhibit immune effectors
ACAID in recipients
name 2 possible ocular side effects of steroids?
cataracts
steroid induced glaucoma
