Cornea Lectures Flashcards
What are the two main divisions of the human immune system?
Innate immunity
Acquired (cell-mediated, humoral) immunity
What are the key characteristics of the innate immune system in terms of line of defence, mobilisation and pathogen exposure?
1st line of defence
Rapidly mobilised
No prior pathogen exposure needed
Does the innate immune system target specific pathogens? Which pathogens evade this system?
Non-specific
Intracellular pathogens not lysed
What physical barriers are in place to prevent pathogen entry? Which chemicals are produced in response to attempted entry?
Skin, eyelids, tears
Antibodies (from B cells), cytokines
What are the fluid and protein components of the innate immune system?
Blood, aqueous humor
Complement, mannose-binding lectin, lysozymes, anti-proteases
How does the complement cascade respond to detecting antigens?
Binding to antibodies
What is the action of lysozymes and what enzymes counteract their effect?
Lysing invading pathogens
Counteracted by anti-proteases
Which cells make up the innate immune system?
Phagocytes
Cytotoxic cells: Leucocytes, macrophages, natural killer cells
Which cells of the innate immune system are primary scavengers? What is their action?
Neutrophils
Attracted to inflammation sites by cytokines, release free radicals and proteases
What are the two main antigen-presenting cells in the innate immune system?
Macrophages (MHC class II) Dendritic cells
What are the main functions of macrophages?
Cell lysis, clearing antigen-coated cells
Active lymphocytes via cytokines
Trigger acquired immunity via lymphoid tissue
Where are dendritic cells of the innate immune system most often found?
High exposure sites: Respiratory system, digestive tract
After working on tissues where do dendritic cells recirculate to?
Lymph nodes
Spleen
Name a type of dendritic cell and where it can be found.
Langerhans cell
Skin, conjunctiva, cornea (stroma)
How does acquired immunity differ from innate immunity?
Antigen-specific
Forms immunological memory
Defends against both intracellular and extracellular pathogens
How do memory cells improve subsequent immune responses to the same invading pathogens?
Somatic mutations alter antibody, allowing better antigen recognition
Which cells make up the acquired immune system?
Lymphocytes
T cells, B cells
Natural killer cells
What are the functions of lymphocytes?
Recognise foreign antigens on pathogens and secrete cytokines
Which cells are activated by T cells and produce antibodies in acquired immunity? What do they do?
B cells
Counteract foreign antigens, activate other cells
Which polymorphic cells recognise antigens presented by MHC?
T cells
Which MHC classes do T helper cells and cytotoxic/suppressor T cells respond to respectively?
T helper cells: MHC class II Cytotoxic/suppressor T cells: MHC class I
How do cytokines affect macrophages, B and T cells?
T and B cells proliferate
Macrophages are activated
What do MHC classes determine?
Whether pathogen is intracellular or extracellular
Which antibodies are seen in the: (a.) Initial immune response, (b.) Secondary immune response, (c.) Mucosal immune system (e.g. tears)?
(a. ) IgM
(b. ) IgG
(c. ) IgA
Which circulating granulocytes do not need prior activation in acquired immunity?
Natural killer cells
Which cells are natural killer cells effective against? How do they destroy targets?
Tumour cells, virus-infected cells
Direct contact, antibodies
What are the phases of the immune response?
- Afferent phase
- T cell activation
- Effector phase
- Secondary response
What takes place in the afferent phase of the immune response?
Foreign antigen taken from entry site, presented to lymphocytes in lymphoid tissue by APC’s
What do activated T cells do?
Produce cytokines
Stimulate cells to become cytotoxic
What takes place in the efferent phase of the immune response?
T cells induce cytotoxic T cells, B cells and macrophages to remove antigen
Antigen-specific B and T cells appear
How does the secondary immune response differ from the initial one?
More antigen-specific B and T cells recruited quicker
Type and specificity of antibody differs
What do dendritic cells do?
Pinocytosis in ECM Lyses cells in acidic vacuole, puts their antigens on surface via MHC class II
Which immune cells recognise MHC class I (found in all cells) and for which antigens?
CD8 cytotoxic T cell Intracellular antigens (viral, self)
Which immune cells (a.) present, (b.) recognise MHC class II and for which antigens?
(a.) Macrophages, dendritic cells
(b.) CD4 helper T cell
Extracellular antigens (bacteria, fungi)
What are the key characteristics of T cell receptors?
Unique to every T cell to recognise different antigens
via embryonic gene rearrangment
Which are the most important cytokines for T cells? Which one is lost in proliferation?
IL-2, 4, 7
IL-2 lost (activated cytotoxic T cells)
What are the key characteristics of B cell receptors?
Unique immunoglobulin surface antigen receptor
Excreted as soluble antibody
Marks foreign antigens recognised by identical T cell receptor for removal by innate immunity
What is the first stage of the antibody response?
Antigen broken up
Picked up by APC and processed
Presented to T helper cell
What is the second stage of the antibody response?
B cell picks up antigen via antibody, more processing
Activated to divide
What is the third stage of the antibody response?
Antibody-forming cells produce soluble antibody
Some remain on B cell surface membrane
What is the initial immune response to injury and infection?
Inflammation
Pathogen removal by innate immune system
Why are immune cells attracted to the injury site?
Tissue component changes (blood vessels, ECM)
How is acquired immunity activated following injury?
Degraded pathogen antigen transported to lymphoid tissue
What is seen in the first stage of the injury and infection response at the site?
Vascular leaks
Leucocyte activation, adhesion, migration
What occurs after antigen migration in the first stage of the injury and infection response?
Acquired immune system activation in the lymphoid tissue
Inflammation
What is seen in the second stage of the injury and infection response?
Phagocytosis
ECM changes
What is seen in the third stage of the injury and infection response?
Inflammation resolution
Tissue remodeling
What is the definition of immune privilege?
The ability to tolerate the introduction of antigens without eliciting an inflammatory immune response
Which bodily organs demonstrate immune privilege?
Brain Ovaries Testes Pregnant uterus Placenta Eye
Which factors affect immune privilege?
Avascularity, blood ocular barrier (iris, ciliary body, retina)
Local immunosuppressive neuropeptides, cytokines
Less MHC expression, class II APC’s, Langerhans cells
Anterior chamber associated immune deviation, apoptosis
Which immunosuppressive factors are in the aqueous humor?
TGF-beta, alpha-MSH
VIP, CGRP, cortisol
NK Cell Inhibitory Factor
Soluble Fas ligand
What role does TGF-beta play in the immune response?
Inhibits B/T cell proliferation
IL-2 receptor expression
Antibody production
What role does alpha-MSH play in the immune response?
Suppresses pro-inflammatory cytokines (IFN-gamma, IL-1, TNF-alpha)
What role does VIP play in the immune response?
Inhibits IL-2 to suppress lymphocyte proliferation
What role does CGRP play in the immune response?
Inhibits delayed-type hypersensitivity
What role does NK Cell Inhibitory Factor play in the immune response?
Protects corneal endothelium from attack by NK cells
What role does the soluble Fas ligand play in the immune response?
Downregulates inflammatory cytokines (IFN-gamma, IL-1, TNF-alpha)
Kills active lymphocytes
What does ACAID stand for? Which intact organs are required?
Anterior chamber associated immune deviation
Eye, spleen
Which cells begin the process of ACAID? How do they do so?
Dendritic cells
Antigen presentation via the lymphatic system
Which two processes occur in ACAID?
Antibody response induction
Suppression of delayed type hypersensitivity
How is ACAID triggered?
TGF-beta (aqueous humor, tears)
APC response
Thrombospondin
What phases are involved in ACAID?
Ocular phase
Splenic phase A
Splenic phase B
How is the ocular phase of ACAID carried out?
Antigen in anterior chamber captured by indigenous APC’s
Where does the antigen travel to in the ocular phase of ACAID?
Trabecular meshwork to blood to marginal zone of spleen
