M: Adaptive immunity 1 - Week 4 Flashcards
List 3 innate defences to infection found at the ocular surface of they eye
- Lids, tears: wash away microbes, inhibit growth
- Complement: lyses bacteria and enveloped viruses; attracts phagocytes
- Tissue macrophages + Neutrophils: phagocytose microbial survivors
Where on the ocular surfaces is complement found?
in tears and conjunctival tissue
What happens to the level of tissue macrophages and neutrophils when lids are closed?
Increases
List 3 innate defences to infection found at the anterior chamber of the eye
- Structure itself: prevents microbe access
- Complement: lyses bacteria and enveloped viruses
- innate immune system: activated by PAMPs
How much does the anterior chamber of the eye rely on physical and soluble mediators to prevent infection? Why is this the case?
Heavy reliance on physical and soluble mediators because a cellular response would impair vision
How can organisms overcome the innate defences of the eye? (3)
- they gain access to anterior chamber via trauma or blood
- they have specific adhesins for the ocular surface
- they can overcome the innate immune system
In regards to lymphocytes:
A) What immune system are they involved in?
B) Name the 2 types of lymphocytes
C) What are lymphocytes derived from?
D) What do lymphocytes recognise?
E) Where are the 2 types of lymphocytes derived?
A: Adaptive
B: B and T lymphocytes
C: Haemopoietic stem cells
D: Antigen
E: B lymophocytes = bursa. T-lymphocytes = thymus derived
How do the 2 types of lymphocytes bind antigen?
B-lymphocytes: Binds whole antigen
T-lymphocytes: Receptor binds antigen peptide displayed on Antigen Presenting Cells
How many different antigens can a lymphocyte recognise?
A lymphocyte has multiple copies of a unique receptor only, which means that a single lymphocyte can only recognise a single unique antigen.
However, it has multiple receptors for this antigen and can bind to multiple of this particular antigen
How and where are T and B cell receptors generated?
By random somatic gene rearrangements during differentiation in the primary lymphoid tissues (Bone marrow/Bursa for B cells and Thymus for T cells)
When can T ad B cells leave the primary lymphoid tissues after differentiation?
When these cells express receptors for non-self antigens
If they express receptors for self antigens, they are destroyed
Where in the primary lymphoid organs do lymphocytes develop? (3)
- foetal liver
- bone marrow
- thymus
What happens once a lymphocyte is released from the primary lymphoid organ?
Is released as a “Naive lymphocyte” as it hasn’t encountered antigen. It travels to our bloodstream and then either enters the spleen or back into the lymph node, an then travels back to the bloodstream.
It does this until they’ve encountered antigen (in the lymph node or spleen).
Once encountered antigen, the “Activated lymphocytes” travel back to the bloodstream and then start entering the tissues and then circulate between the tissues and bloodstream
Where do naive lymphocytes first interact with foreign antigens? (3)
In the secondary lymphoid organs:
- spleen
- lymph nodes
- molecular associated lymphoid tissues (MALT)
List the 7 lymphoid tissues of the adaptive immune system in the body
- conjunctival associated lymphoid tissue
- adenoid
- tonsil
- lymph node
- spleen
- appendix
- large intestine
Where can you find the 3 eye-associated lymphoid tissues?
- lacrimal gland
- lacrimal drainage system
- conjunctiva
How are lymphocytes spread in the conjunctiva?
Diffusely spread among the cells of the conjunctiva. Found in “follicles”
What name do we often use to refer to the tissues and structures associated with our mucosal tissue?
Common Mucosal Immune System
True/False: There are lymph vessels that drain from the conjunctiva
True
True/False: There aren’t any lymph nodes that drain from the eye and anterior chamber
True
Where do a lot of the antigens present in the ocular departments drain to? What does this mean?
Drain to the spleen. Therefor a lot of immune responses are actually induced in the spleen
Describe the vascularity of the central cornea. Where in the cornea are dendritic cells present?
The central cornea is avascular. Dendritic cells are present only in the peripheral corneal epithelium
Is there any lymphatic drainage in the cornea? Explain
No lymphatic drainage. Most of the dendritic cell antigens from the cornea are drained through the blood and delivered to the spleen
Why are immune responses in the intraocular compartment of the cornea often suppressed?
Because otherwise the immune activation would damage/impair our vision
What do B-lymphocytes mature into and what do they produce? How are they important?
B-lymphocytes mature into plasma cells (mature B cells) that produce antibodies, which are important in controlling and removing extracellular pathogens
Why can’t antibodies remove intracellular pathogens?
Because they cannot penetrate into cells (they are too big)
What chains do antibodies consist of? (2)
- 2 identical heavy chains, and
- 2 identical light chains
What 2 distinct regions do antibodies have? How many forms can these 2 regions take
- Fc (constant region): can take 5 forms/isotypes
- Fab (variable/antigen-binding region): can take an almost infinite variety of forms
Where in the Fab region of the antibody does the antigen bind?
Binds in the “pocket” of the heavy and light chain
- this pocket is generated from random rearrangements that happen when the B cell undergoes maturation
How many possible antigen binding sites can be generated in B cell maturation? What does this mean?
Around 10 to the power of 11. In other words we can make 10^11 different antibodies
When is a B-lymphocyte unable to change its Fab region? Can it still change Fc region in this circumstance?
Once the B cell is expressing a functional antibody and uses that antibody as the receptor for a particular antigen, it cannot change Fab anymore. However it can still change Fc.
If B cells in the bone marrow bind to self antigen, what happens?
They get deleted
What causes different B cells to make different antibodies?
Differences in the variable region (Fab) that binds specific antigen
What are the 5 antibody isotypes? What determines the isotypes?
Determined by the constant region (Fc) of the heavy chain:
- IgM, IgG, IgA, IgD, IgE
How do phagocytes recognise the Fc region of antibodies?
They have Fc receptors that recognise the Fc region of the antibodies
- Fc receptor (FcR) that binds an IgG antibody = Fc y receptor
- Fc receptor (FcR) that binds an IgE antibody = Fc alpha receptor
What 2 things does the Fc region of an antibody bind?
- phagocytic receptors
- complement proteins
How do antibodies control extracellular pathogens? Consider the isotypes (5)
They:
1. Prevent pathogen binding at mucosal surfaces (IgA)
2. Neutralize the action of toxins (IgA, IgG, IgM)
3. “Opsonise”: The Fc region binds directly to Fc receptors on phagocytes (IgG)
4. Trigger the complement cascade (IgG, IgM)
5. Induce release of cytotoxic products from macrophages and NK cells (by IgG binding FcyR) and eosinophils (by IgE binding FceR)
Explain how antibodies outside the mucosal tissue protect from invasion
- viruses, bacteria and toxins are trying to invade the tissues
- antibodies such as IgA are secreted across the epithelial cells/mucosal surface
- IgA binds to the bacteria, toxins and viral pathogens, this prevents them from binding the mucosal surface (i.e. epithelial cells)
Explain how antibodies inside the mucosal tissue protect from microbial invasion via phagocytosis
- microorganisms that cross the mucosa into the tissue
- may be coated with IgG, which can then bind to the FCy receptor on a macrophage
- This induces phagocytosis and killing through the recruitment of lysosomal proteins
Explain how antibodies inside the mucosal tissue protect from microbial invasion via complement cascade
- bacteria coated with either IgG or IgM molecules can activate the cascade
- results in opsonisation of the bacteria and phagocytosis/lysis of the bacteria
Explain how antibodies inside the mucosal tissue protect from intracellular infection with viruses
- infected host cells will display viral proteins on their surface
- viral proteins bind to IgG, which can activate complement cascade or the NK cells
Explain how antibodies inside the mucosal tissue protect from parasitic infections
- IgE responses are important in protection against parasite
- IgE binds to the parasite or antigen on parasite
- Once bound, the IgE will bind to the FceR on the eosinophil and activate it
