M: Adaptive immunity 2 - Week 5 Flashcards
How does the antigen specificity of the antibodies secreted by the plasma cell compare to that of the molecule used as the antigen receptor for the B cell?
Exactly the same
What is the antigen receptor for B cells?
Membrane bound antibodies, specifically IgM antibodies
What aspect of antigens are recognised by B cells?
Their shape (conformation)
What does a B-cell do when it first encounters antigen? (4)
- it endocytoses the antigen complex
- it then undergoes rounds of proliferation (about 8-10 generations in 5 days)
- therefore after initial encounter with the antigen, a whole pool of B-cells expressing the receptor for that antigen will be produced (in 5 days)
- the B cells then mature into mostly plasma cells and also a few memory cells
Describe the free antibodies secreted by plasma cells
The free antibodies (IgM) are exactly the same as the membrane-bound antibody that was present on the B-cell
What is the purpose of memory cells?
They persist to combat next infection
List the 3 features of the antibody response to infection
- Enhanced secondary response
- Isotype switching (IgM produced first)
- The development of memory
Describe the antibody response to first infection
When you encounter the first infection, it takes time before you can measure antibody levels in the serum or tears
- the first batch of antibodies secreted are IgM antibodies
- after a while, the immune response decreases as we are eliminating and controlling the infection
- we also see the production of other antibodies (like IgG and IgA)
Describe the antibody response to second infection
Memory response kicks in
- the memory cells are activated much more quickly and start to rapidly secrete IgA antibodies
- there is a strong magnitude in the release and secretion of IgA antibodies
In our blood, which antibody isotype has the highest serum concentration? (i.e. most of the antibody in our blood is which isotype?)
IgG
In regards to IgA: A) Where is it found? B) Does it activate the complement cascade? Explain C) is it a good opsonin? D) is it a good antimicrobial? E) is it involved in allergic activity?
A) is present in our secretions in the tears, respiratory tract and GI tract
B) Does NOT activate cascade b/c it’s found in eyes and tears. Activating cascade would lead to chronic inflammation and impairment of vision
C) is NOT a good opsonin
D) Yes. Very.
E) No
In regards to IgG: A) Where is it found? B) Does it activate the complement cascade? C) is it a good opsonin? D) is it a good antimicrobial? E) is it involved in allergic activity? F (Bonus)) Can it cross the placenta?
A: Blood tissues/Blood B: Yes C: Yes D: Yes. Very E: A bit. F: Yes
In regards to IgM: A) Where is it found? B) Does it activate the complement cascade? C) is it a good opsonin? D) is it a good antimicrobial? E) is it involved in allergic activity?
A: Blood B: yes. A lot C: a bit D: Yes (two ++, but not three +++) E: No
In regards to IgE: A) Where is it found? B) Does it activate the complement cascade? C) is it a good opsonin? D) is it a good antimicrobial? E) is it involved in allergic activity?
A: Basophil. Mast Cells. B: No C: No D: For parasites (+) E: Yes. Very much so.
Explain the role of IgE in allergic reactions
IgE triggers activation of Mast cells which release histamines
How do the levels of IgG, IgA, IgM and IgE change with:
A) Bacterial infection
B) Allergic reaction
C) Viral
A: IgA increase, IgG/IgM slight increase, IgE normal
B: IgG/IgE slight increase, IgA normal, IgM absent
C: IgG/M/E increase, IgA normal
What is sIgA and what does it do?
Secretory IgA = the principle specific protective mechanism operating at the conjunctival surface
- binds microbial adhesion structures to prevent adhesion to mucosal epithelium
- may also bind toxins to prevent attachment to mucosal cells
Explain the mechanism of how IgA is transported across the mucosal epithelium (5)
- sIgA dimers are secreted into interstitial space by plasma cells
- dimer binds to the J-chain of the poly Ig receptor on the surface of acinar epithelial cells
- sIgA receptor complex is endocytosed and transported across the cell, bound to the membrane of the transport vesicle, which fuses to the plasma membrane at the luminal surface
- IgA dimer is released into acinar lumen with the “secretory component”
- The presence of the secretory component protects against proteolytic cleavage by acinar luminal enzymes
What is the “secretory component” involved in IgA transport? What does it do? (2 functions)
is a portion/part of the polymeric Ig receptor that remains attached to the IgA once it has transported through the epithelial cells into the apical side
It helps to anchor the IgA into the mucus and also protects it against proteolytic degradation/cleavage
What is sIga important in protecting?
the corneal surface of the eye as well as other mucosal sites
In what layer of the tear film would we expect to see lots of IgA?
Mucin layer
Define epitope
part of antigen that antibody/T-cell receptor binds to
Define immunogenic
something that elicits a robust immune response
How does a T-cell know that it is harbouring a pathogen? (4)
- proteins present in the cytosol, or in vesicles are catabolised to small peptides
- These become complexed with carrier molecules (MHC) and are transported to the cell surface
- Any pathogen the cell is infected with or engulfs also provides peptides to be carried to the surface by MHC molecules
- T cell receptors (TCRs) recognise pathogen peptides displayed on the cell surface in MHC molecules
What is the difference between T and B-cell binding? In terms of what part of the antigen they recognise
T cells can only bind short linear epitopes while a B cell may recognise the structure of a protein or carbohydrate
This means that for a T-cell to recognise antigen, it has to be degraded first into short peptides (fortunately the APC does this function)
List the roles of CD8+ T lymphocytes (cytotoxic lymphocytes) (1)
- bind and kill tissue cells infected with intracellular pathogens and neoplastic cells whose foreign peptides are displayed on the MHC molecules of the infected cell
List the roles of Cd4+ T lymphocytes (Helper T cells)
- help B cells produce antibody
- activate cells of the innate immune system
- aid production of cytotoxic T cells
- regulate unwanted responses [regulatory T cells)
What does CD stand for?
Cluster of Differentiation
How do APCs activate T cells?
APCs have internalised antigen in the tissues and will migrate via the lymphatics to the lymph nodes to activate T cells
True or False: B cells can recognise free antigen whereas T cells cannot
True
In regards to MHC molecules:
A) What encodes them?
B) Describe their structure
A) a complex set of genes located on chromosome 6
B) contains 2 helixes that form the “peptide binding cleft”, into which peptides can bind
If we all express different MHC molecules and have a different peptide binding cleft, why are we still able to respond to the same antigens?
Because even though we have different MHC molecules, we simply use slightly different peptides to respond to the same antigen
What are the 2 types of MHC molecules we express? And:
A) What expresses them?
B) Describe their structure
MHC Classes I and II
A) Class I molecules are expressed on almost all nucleated cells (incl. APCs) whereas Class II molecules are only expressed on APCs
B) Class I molecules have an alpha 1, 2 and 3 domain that is complexed with a beta 2 microglobulin molecule while Class II molecules just have an alpha and beta chain
What are MHC molecules also referred to as in humans?
HLA (Human leukocyte antigen)
How are HLA gene products expressed?
Co-dominantly
In regards to MHC (HLA) alleles:
A) Are they inherited or sporadic?
B) What can they bind?
C) What do individuals with different alleles bind?
A: inherited
B: a particular allele can bind a diverse but limited range of peptides
C: individuals with different alleles bind a different but still diverse range of peptides
What is the purpose of the antigen-binding site created for the T cell receptor
Created so that it can bind to the MHC molecule AND the peptide
How does polymorphism affect the binding of certain peptides?
Alters or abolishes the binding of certain peptides
How does an individual’s HLA haplotype affect susceptibility to disease? (4)
Genetic polymorphisms in MHC affect:
- ability to generate an adaptive response
- resistance or susceptibility to infectious disease
- resistance or susceptibility to allergic disease
- resistance or susceptibility to autoimmune disease
What cells can be APCs?
dendritic cells, macrophages, B cells
How are both dendritic cells and macrophages found in most tissues? Incl. ocular tissues
As networks. This allows them potential access to intraocular antigens
List the steps in APC activation of T cells (3) Talk about endogenous vs exogneous antigens
- antigens found external to APC (exogenous antigen) are taken up into endosomes and presented by MHC class II
- Some antigens are present free in the cytosol (endogenous antigens) and are presented by MHC class I
- Whichever location, the antigen is degraded internally and displayed as peptides to T cells on MHC molecules
How do CD4+ T cells recognise antigen? What about CD8+ T cells?
CD4: recognise antigen when displayed bound to class II MHC molecules
CD8: recognise antigen when displayed bound to class I MHC molecules
How doe CD4/CD8 T cells discriminate between MHC class I or II?
The CD4/8 molecules function as a co-receptor for antigen, in a way. The CD4 T-cell uses its unique TCR to bind to MHC class II and peptide
- uses its CD4 molecule to bind to the conserved region on the MHC class II molecules
- any CD4 T-cell can bind to any MHC class II molecule, b/c that’s the “conserved” region. However, the TCR is unique to that MHC and that peptide
How are MHC class I and class II molecules derived?
MHC Class I: derived from cytosolic processing
MHC Class II: derived from endosomal processing
What type of antigens do NOT require processing to activate T cells?
Super antigens
