FINAL IMMUNITY DECK Flashcards
Location of molecules on the complex between a dendritic cell and a cytotoxic T cell?
Part binding to the dendritic cell = MHC class I molecule
Side chain co receptor on the left = CD8
Part bound to cytotoxic T cell = T cell receptor
Location of molecules on the complex between a helper T cell and a dendritic cell?
Part binding to the dendritic cell = MHC class II molecule
The co receptor side chain = CD4
Part bound to cytotoxic T cell = T cell receptor
Helper T cells and Cytotoxic T cells are derived from which pluripotent cell found in the bone marrow?
Haematopoietic stem cell
To which immune cell lineage do Helper T cells and Cytotoxic T cells belong?
Lymphoid
The other types are B cell or natural killer cells
Name the two other immune cell lineages derived from the Haematopoietic stem cell?
Myeloid and erythroid
Seven cell types belonging to the innate immune system?
Mast cells, dendritic cells, neutrophils, macrophages, NK cells, eosinophil,
basophils
Where is the Fab domain, the Fc domain, the heavy and light chains, the VH and VL regions of the Fab domain on an IgG immunoglobulin molecule?
Fab domain = top half of the Y
Fc domain = bottom half of the Y
Heavy chain is top part of arm of Y
Light chain is lower part of arm of Y
The VH region is the very top of the arm on the heavy region in the fab domain
The VL is the very top of the light chain in the fab domain
What is opsonisation?
Opsonisation is the deposition of molecules on the surface of a cell, enhancing uptake by phagocytes
Name the 2 types of soluble host molecule involved in opsonisation
Complement (C3b) and antibody
How is the bacterium B. pseudomalleu arable to avoid opsonisation?
Polysaccharide capsule blocks opsonisation
What is ADCC?
antibody dependent cell mediated cytotoxicity
Which class of immunoglobulin is involved in parasite immunity and binds to the FcεR1 receptor on the surface of Mast cells, basophils and eosinophils leading to degranulation?
IgE
What’s the molecular formula of IgE?
ε2κ2 or ε2λ2
Activating Fc receptors signal through which immune cell-activating motif?
ITAM (Immunoreceptor Tyrosine-Based Activating Motif)
A linear polysaccharide chain indicates a bacteria will have what types of surface structures?
Capsular polysaccharide and lipopolysaccharide
What molecule anchors bacteria surface structures?
Lipid A
How and where might the DNA be modified in mammalian DNA?
The CG motif may be methylated
How does this modification affect the interaction of DNA with cells bearing Toll-like receptor 9?
Only un-methylated CG motifs are recognised by TLR9
Pattern recognition molecules in the host can be categorised as cell-associated or soluble, Name a class of cell-associated pattern recognition molecules?
Toll-like receptors, NOD-like receptors, C-type lectin receptors, scavenger receptors, or N-formyl met-leu-phe receptors
How might the extracellular domain of Toll-like receptors be modified to recognise different molecules?
By the insertion of amino acids and/or glycosylation
what is the function of the MD-2 accessory factor?
To bind to lipid A of lipopolysaccharide
Give an example of a toxoid vaccine?
Tetanus
List disadvantages of formaldehyde toxoids
Must balance cross-linking with retention of antigenic structure
Batch-to-batch variation
Reversion
Requires pure toxin as the starting point, therefore need to grow the pathogen and purify and handle the toxin
What is antigenic mimicry and an example?
Many pathogenic bacteria are able to avoid the induction of an adaptive immune response
This is done by the bacteria have surface molecules that resemble the molecules on the
surface of host cells
Neisseria menigitidis - sialic acid or Streptococcus pyogenes - hyaluronic acid
What does the acronym HIV stand for (provide the full name), what disease does HIV cause (provide the full name), and from which virus of primates is HIV thought to have arisen (provide the full name)? [3 marks
The two viral envelope glycoproteins are shown as X and Y in the above figure are critical for HIV infections. Name the transmembrane glycoprotein X and docking glycoprotein Y
Human Immunodeficiency Virus, causes Acquired Immune Deficiency Syndrome, thought to have arisen from Simian Immunodeficiency Virus (SIVcpz)
ANSWER: X = gp41; Y = gp120
Why is HIV so bad for humans?
It is the only virus that infects cells of the immune system (specifically CD4 T cells)
The phenomenon of using host cell receptors for tissue invasion is known as what?
Tissue Tropism
Epithelial cells in the small intestine express CCR5 which allows the HIV viral envelope
glycoprotein gp120 to bind and for transcytosis of the virus to occur, What is CCR5?
CR5 is a CHEMOKINE receptor
It is also why gp41 binds to
Name a second host cell receptor bound by gp120 and name the cell type on which this receptor is displayed?
To which cell surface receptor of a dendritic cell does gp120 bind?
CD4 on CD4 T cells
C-type lectin receptor
Immunity to viruses is maintained by which three components of the innate immune system?
Type 1 interferons
Complement
Natural Killer cells
Adaptive immunity to viral infection is maintained by which two components of the cellular and humoral immune systems?
Cytotoxic T lymphocytes (CTLs) or CD8 T cells
Antibody
Describe briefly two mechanisms through which antibodies provide immunity to viral infections?
Neutralisation
Natural Killer cell-mediated ADCC
AIDS patients typically suffer from opportunistic fungal infections due to their impaired immunity, Name 3 opportunistic yeast pathogens of AIDS patients?
Candida, Cryptococcus, Histoplasma
The ability of yeast pathogens to switch between yeast and filamentous growth forms is known as what?
Dimorphism
Name an opportunistic mould pathogen of immunocompromised patients?
Aspergillus
ulmonary infections by moulds are typically found in patients with which type of cancer?
Haematological malignancies
Which two types of immune cells are crucial for maintaining pulmonary immunity to fungal pathogens?
Macrophages and neutrophils
What is the likely chemical feature of the CpG DNA if its effective in stopping disease?
DNA where most of the CG motifs are not methylated, so it’s recognised by toll like receptor 9
Summarise the likely mechanism explaining the effect of dosing with CpG DNA?
Put in the main deck
The CpG DNA binds to TLR9 (1 mark) and activates NFκB via the MyD88 adapter protein (1 mark).
The activated NFκB binds to genes regulating their expression (1 mark).
This results in the production of cytokines like IL-1, IL6, TNF (1 mark) and also chemokines, adhesion molecules and co-stimulatory molecules.
These provide protection against disease.
Give two examples of other molecules that might be used in place of CpG to elicit a similar effect?
glycolipids, lipopeptides,
If a bacteria struggles to grow in bacteria would mean what if they had a mutant SodC enzyme as well?
Put in the main deck
The bacteria are likely to be intracellular - in the phagolysosome
SodC enzyme catalyses The conversion of superoxide to peroxide
Catalse may also be acting
How might a toxoid vaccine be generated? and the benefits
By chemical toxoiding (formaldehyde) (1 mark) or by using a modified gene encoding a genetic toxoid (1 mark).
Ease of production and high yield
- Molecular structure more similar to the active toxin
- Reproducible properties
- No reversion
What type of immune response would you expect a toxoid vaccine to induce and how will this protect against disease?
Antibody response.
By neutralising the toxin.
Cells of the innate and adaptive immune system are derived from the pluripotent
haematopoietic stem cell, Antibody-producing B cells are derived from which lineage of the HSC?
Lymphoid lineage
Name the three other cell types from the lymphoid?
Two of these cell types are cytotoxic, provoking apoptosis of infected cells. What two components of their granules provoke cytotoxicity?
CD4 T-cells, CD8 T cells, Natural Killer cells
Perforins and granzymes
Structure of an IgM antibody?
5 Y’s conjoining into the centre = pentameric
(μ2κ2)5 or (μ2λ2)5
Structure of IgG or IgA antibody?
Y shaped
IgA can also be 2 Y shaped connected to each other
IgA = (α2κ2)2 or (α2λ2)2
IgG = (γ2κ2 )or (γ2λ2)
Which is the most abundant class of antibody present in human serum?
IgG
Which of the two classes of antibodies shown contain J chains?
IgA and IgM
Which of the three classes of antibody shown contains secretory elements
IgA
To which receptor does the secretory element bind for antibody transcytosis across membranes?
Polymeric Ig receptor
The antigenic determinant to which an antibody binds is better known as what?
Epitope
The Fc region is crucial for delivering the effector functions of an antibody. Which two mechanisms deliver these effector functions? Provide the mechanisms in full, not just their abbreviations?
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Complement Mediated Cytotoxicity (CMC)
Visual differences in a mouse, chimeric (human and mouse) and a humanised antibody?
Mouse = all murine protein
Chimeric = mainly human protein but a bit of murine protein at the top of Y’s
Humanised = nearly all human protein, couple stripes of murine protein near top of Y’s
Humanised antibodies are produced by grafting which part of a mouse antibody into a human
antibody framework?
Complementarity Determining Regions or CDRs
Give two reasons why a mouse antibody must be humanised if it is to be used in humans?
Human Anti-Mouse Antibody (HAMA) reactions and loss of effector functions if Fc domain is mouse
Name two antibody-based drugs and the human diseases they are used to treat?
Rituximab (Non-Hodgkin’s Lymphoma) and Herceptin (Breast cancer)
Provide an example of a disease causing bacterium which can be prevented using a licensed vaccine based on bacterial polysaccharide? And main limitation of this strategy? And why is it that reason? And how can this be overcome?
`Put in the main deck
Disease caused by Streptococcus pneumonia
They work very poorly in infants
They are T-cell independent antigen. They induce only an antibody response without T-cell involvement or memory
By conjugating the polysaccharide to a protein carrier. The resultant glycoconjugate induces a T-cell response
The “non-toxic NetB mutant is a site-directed mutant. What generic term do we use for this type of toxoid vaccine?
Genetic toxoid
How does formaldehyde treatment generate a vaccine?
Put in the main deck
By creating intra- and inter-molecular linkages between molecules. Formaldehyde cross- links amino groups in proteins with other nearby nitrogen atoms in proteins through a -CH2- linkage
What is the difference between homo- and hetero-dimeric TLR complexes?
They consist of identical or non-identical subunits
Name 3 ligands bound by TLRs?
CpG
DNA
Lipid A (lipopolysaccharide)
What molecules are responsible for signal transduction from the TLR?
Adapter proteins like MyD88 or TRIF
At the end point of the signalling cascade NFkB can be activated. What is the next step in the cascade?
The released p50/p65 protein migrates into the nucleus and activates the expression of genes encoding inflammatory mediators
The ‘Spanish’ flu pandemic of 1918 to 1920 was caused by a highly virulent and transmissible H1N1 strain of the influenza virus, What are H and N in H1N1?
Which of these mediates entry of the virus into cells of the respiratory epithelia and which promotes viral release?
To which receptors on human respiratory epithelia does the virus bind?
Hemagglutinin (H) and Neuraminidase (N)
Hemagglutinin (H) mediates entry and Neuraminidase (N) promotes release
To those that have the α-2,6 sialic acid linkage to galactose
Seasonal flu epidemics occur when point mutations accumulate in H and N. These point mutations lead to a process by which neutralising antibodies are unable to block entry of the virus into cells of the respiratory epithelia.
What is this process known as?
Antigenic drift
Flu pandemics occur following genome re-assortment of avian and human influenza viruses. In which mammalian host does genome re-assortment occur?
Pig
What feature of the respiratory epithelium of the pig enables genome re- assortment of human and avian strains to occur?
vian viruses prefer the α-2,3 sialic acid linkage to galactose. Pigs express both α-2,3 and α-2,6 sialic acid linkages to galactose on respiratory epithelia thereby enabling binding and entry of both human and avian strains of the virus
Name the 3 major components of innate immunity to viruses?
And of which of these belongs to the lymphoid lineage?
Complement, Type 1 interferons, Natural Killer (NK) cells
NK cells are part of the lymphoid lineage, with the other 2 parts of this lineage being T-lymphocytes and B-lymphocytes
Major adaptive immunity to viruses is mediated via which cellular [1 mark] and humoral [1 mark] components of immunity?
CD* (Cytotoxic T cells/CTLs)
Antibody
Through which type of molecule does the virus- infected cell display antigen? What’s the other type of antigen-displaying molecule existsName this class of molecule?
MHC Class I
MHC Class II
Name 2 antigen-presenting cell types in which this MHC class II is expressed?
And Which cellular compartments of the cell does this second class of molecule monitor for foreign antigen?
Macrophage and dendritic cells
Compartments of the endosomal and lysosomal pathways
The adaptive immune cell recognises viral peptide displayed by the infected cell via a complementary cell surface molecule, what’s this immune cell called and what is the complementary molecule?
Cytotoxic T lymphocyte (CTL) or CD8 T cell
T cell receptor (TCR)
The process of killing uses the same cellular machinery that gives rise to programmed cell death. This process of programmed cell death is known as what?
Apoptosis
The classical pathway of complement activation is associated with the binding of antibody, Name the other pathways of complement activation?
Alternative and lectin
Which of the following components can bind to bacterial cells and activate the complement pathway?
C3, mannose binding lectin, IgM antibody
Give an example of an effector function of complement, and name a key component of complement that is directly involved in this effector function?
Inflammation – C3a C5a or Opsonisation C3b or Lysis (MAC) – C5-C9
How does the membrane attack complex cause bacterial killing?
By forming pores in the bacterial cell wall
What types of bacterial disease are associated with C9 deficiency?
Meningitis and sepsis caused by Neisseria
Explain briefly how biotechnology is helping to provide improved toxoid vaccines?
Genetic toxoids, where mutations are introduced into the encoding gene at triplets encoding functionally critical amino acids, to reduce toxicity
Give an example of a bacterial polysaccharide that is targeted by a protective immune response.
LPS O-antigens, capsular polysaccharide from a range of bacteria e.g. Streptococcus pneumoniae
At the cellular immunology level, what is the main problem associated with the induction of long-lasting immune responses to polysaccharides?
How can this problem be solved?
How does this alter the processing of the polysaccharide antigen?
Put in the big deck
Lack of T-cell involvement
By linking to a protein, to create a glyco-conjugate
It is believed that the glycol-conjugate is internalized into an endosome of the B cell. It is processed into glycanP saccharides, peptides and glycanP-peptides.
5
There is MHCII presentation of glycanP-peptide to CD4+ T cells. Activation of the T cell by the carbohydrate/MHCII results in T-cell production of cytokines which mature the B cell to become a memory B cell.
What does the acronym ITAM stand for?
Immunoreceptor Tyrosine-based Activation Motif
Following antigen binding by the BCR, the cytosolic tails of the ITAM are phosphorylated (indicated by red dots) by the membrane-bound enzymes Blk, Fyn, or Lyn. What is the collective name for this family of enzymes?
Src-family tyrosine kinase
The enzymes phosphorylate equally spaced amino acid residues within a consensus sequence on the tail of the ITAM. Which specific amino acid residues are phosphorylated?
Tyrosine
The phosphorylated amino acids then allow binding and activation, via transphosphorylation of tandem SH2 domains, of a molecule indicated by the crosses shown in C? Name this molecule [
Syk
an alternative molecule, ZAP-10, is found in which specific cells of the adaptive immune system?
T-cells
Name another cell surface receptor that signals through the ITAM or an ITAM- like motif ?
Dectin-1, Dectin-2
They can aid in the recognition of fungal zymosan
How many potential antigen-binding sites does this pentameric structure have?
10
Which immunoglobulin isotype can be a monomer, dimer or trimer?
IgA
Which immunoglobulin isotype is particularly involved in defence against schistosomes, but is also involved in common allergic diseases such as allergic asthma?
IgE
Which immunoglobulin isotype binds to the receptor FcγRII B2 (CD32) present on macrophages, neutrophils and eosinophils?
IgG
Which immunoglobulin isotype accumulates in the foetus before birth?
IgG
Which immunoglobulin isotype acts in the defence of mucosal surfaces?
IgA
Name the protease that cleaves a immunoglobulin into the three pieces?
Papain
Splitting it into 2 parts which are part of the F(ab) domain
And the other piece part of the Fc domain
Name the protease that cleaves the immunoglobulin into 2 pieces F(ab)2 and pFc?
Pepsin
In blood groups what’s the universal donor and the universal recipient?
O is donor
Ab is recipient
If a question comes up on blood groups it’s the 2016 test
How is the diphtheria vaccine currently in use prepared?
Diphtheria toxin is purified from a culture of Corynebacterium diphtheriae. The toxin is treated with formaldehyde, inactivating the toxin but preserving immunogenicity
What type of improved diphtheria vaccine has been devised?
A genetic toxoid, where a functionally critical amino acid is substituted to abolish toxicity
good picture of complement cascade on 2016 paper
ok
Fred has a mutation in the complement component C3. Provide two possible bacterial infections you might expect him to suffer from?
Respiratory tract infections and meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae,
For initiation of the complement cascade by the classical pathway, what type of host molecule is required?
Antibody, which binds to the microbe
How does the complement cascade cause direct killing of bacteria?
The membrane attack complex (MAC) forms a pore in the bacterial cell wall
How does the component C3b promote bacterial killing by phagocytic cells?
C3b can directly opsonise bacteria and promote uptake via C3b receptors
Which cell types of the myeloid lineage are antigen-presenting-cells?
Dendritic cells and macrophages
Which cell types belong to the adaptive immune system?
B and T cells
Make sure to learn diagram with all lineages
ok
Which cell types of the innate immune system release histamines?
Mast cells and basophils
Mast cells and basophils de-granulate when antibody binds to receptors on their cell surfaces. Which immunoglobulin class is involved in this sensitisation process?
IgE
B cells, when activated in the lymph nodes, differentiate into antibody- producing effector cells. What are these effector cells known as?
Plasma cells
A T-cell interacts with antigen via its T-cell receptor comprising variable and transmembrane regions. Unlike the TCR, the cell surface receptor of a B cell (B-cell receptor) is comprised of what?
Antibody
Which sub-set of CD4+ T-cells produces cytokines that activate B cells and inhibit monocyte and macrophage activation?
TH2 cells
What is MBL, and to which group of organisms in particular does it bind?
Mannose binding lectin, binds in particular to fungi
What are MASPS?
Mannose binding lectin-Associated Serine Proteases
What does VSG stand for?
Give the name of a human protozoan parasite that expresses VSGs?
Explain briefly what this diagram shows, and why this phenomenon occurs during infection by the parasite identified in
Variable Surface Glycoprotein
Trypanosome
Trypanosomes comprise Variable Antigen Types that express different VSGs.
aa During infection by, for example, a T. brucei VAT displaying VSG , anti-VSG
antibodies will be produced. This is followed by a decline in VSGa parasite 4 ac numbers.TheVSG VAT then switches to a VAT displaying VSG , which is then followed by an anti-VSGc antibody response, and a decline in the VSGc VAT. This process of VSG switching and antibody activation continues as different VATs are generated by the parasite during the infection process.
Table on the humanised monoclonal antibodies is on the 2017 paper
OK
How are the peptides generated in the antigen-presenting-cell?
Proteins are processed by the proteasome in the cytoplasm of the cell
Where in the antigen-presenting-cell are the proteins located for processing into peptides?
They are located in the cytosol of the host cell
What is the action of the CD8+ T-cells after they are activated?
They are cytotoxic, killing cells which display the same peptide that is involved in their activation. Killing mechanism is perforins and granzymes.
Give 2 examples of the ways in which vaccines can be devised which activate CD8+ T-cells?
Using live attenuated microbes
Using naked DNA
Using dendritic cells exposed to antigen ex vivo
Give 4 mechanisms through which antibodies are able to protect against disease?
agglutination, opsonisation, neutralisation, complement fixation, inflammation, antibody-dependent cell-mediated cytotoxicity (ADCC)
What type of experiment can be carried out to prove that antibodies are able to protect against disease?
Passive transfer of sera from immunised to non-immune animals results in the transfer of protection
How would you expect antibodies against diphtheria toxin to protect?
By neutralising the toxin
In the past, antibodies against diphtheria toxin were used to treat disease. What was the main problem with this treatment?
The antibodies were raised in horses, and the use of this serum in humans could result in serum sickness
Which type of T-cell can augment antibody production by B-cells?
CD4+ T-cells
In which system of the body does dendritic cell activation of B cells occur?
In the lymphatic system (you can be more specific than this e.g. within the germinal centres)
A mature B cell that hasn’t yet encountered antigen is referred to as what?
Naïve
Thymocytes are hematopoietic progenitor cells present in the thymus. Into which cell type do thymocytes differentiate?
T-lymphocytes or T-cells
Name the region of an antibody responsible for binding to receptors on the surface of phagocytic cells ?
Fc region or Fc domain
Name the region of an antibody which binds to antigen
F(ab) region or F(ab) domain. Variable heavy and light chains would also be acceptable.
The antigenic determinant bound by an antibody is known as the epitope. What name is given to the corresponding epitope-binding region on an antibody?
Paratope
The hypervariable loops in the VH and VL chains of the antigen-binding region of an antibody are known as what?
Complementarity Determining Regions
Which evolutionary conserved family of proteins, considered functional ancestors of antibodies, are also able to activate the classical pathway as well as antibody?
Pentraxins
To which arm of the immune system are NK cells considered to belong and why?
Innate, because they don’t require prior activation unlike B-cells and T-cells
Once activated to kill the target cell, the NK cell releases which two molecules ensuring the target cell is destined for death?
e) Which other immune cell type uses the same mechanism for killing virus-infected or cancer cells?
Granzymes and Perforins
Killer T-cells, CD8+ T-cells or Cytotoxin T-cells
a procedure for the in vitro production of antibodies with pre-defined specificity?
ame the two scientists who pioneered the procedure
Hybridoma technology
George Kohler and Cesar Milstein
From which secondary lymphoid organ are antibody-producing B cells extracted for fusion with myeloma cells following mouse immunisation
Spleen
list 3 key properties each for myeloma cells and B cells which enable the production and selection of the hybrid antibody-producing cells
Myeloma cells:
Infinite lifespan
Not able to produce antibody (Ig-)
HGPRT -
B cells:
Finite lifespan
Capable of producing antibody (Ig+)
HGPRT
Following fusion of the B cells with the myeloma cells they are grown in which medium to allow selection of the immortilised antibody-producing hybrid cells?
Hypoxanthine-Aminopterin-Thymidine medium or HAT medium
Name in full the component in the medium which blocks nucleic acid biosynthesis
Aminopterin
The immunoglobulin class secreted by Clone 2 is M (IgM). Given that the molecular weight of a single Y-shaped Ig in an IgM molecule is 180kDa, what is the approximate molecular weight of an intact IgM molecule?
IgM molecules are pentamers comprising 5 Y-shaped Ig molecules so 5 x 180kDa = 900kDa
Give the 3 possible valencies for an IgA antibody
2, 4 and 6
If asked examples of ligands that can be bound by the extracellular domains of TLRs ?
It’s on 2018 paper
The binding of which ligand to TLR4 is enabled by MD-2?
Lipopolysaccharide
In addition to ligand binding, why is TLR dimerization required?
To enable signalling via the intracellular signalling domain
The signalling cascade, activated after TLR binding, results in the production of broad groups of molecules by the activated cell. Give two examples of these broad groups of molecules?
Cytokines, chemokines,
Both alhydrogel and MPLA boost the antibody response. What name is given to these types of molecules that potentiate the immune response?
What is the most likely mechanism by which alhydrogel boosted the antibody response?
What is the most likely mechanism by which MPLA boosted the antibody response?
MPLA is derived from lipopolysaccharide (LPS). However, unlike LPS, MPLA shows low toxicity. What is the structural difference between LPS and MPLA that accounts for this reduction in toxicity?
Put in main deck
Adjuvants
By forming a gel-like matrix and acting as a depot, then releasing antigen over a prolonged period
By acting as an immune stimulator/modifier. MPLA is a Toll agonist, activating signalling pathways. This results in cytokine production which modifies the response
MPLA lacks one of the phosphate groups of LPS
How are proteins converted into peptide by the proteasome?
The proteasome has protease activities
Provide a consequence of peptide presentation to CD4+ T cells?
he CD4+ T-cells produce cytokines that shape the immune response
Which pathway would you expect to be activated if there is a strong antibody response to a bacterium?
The MHC Class II/ CD4+ T-cell pathway
The point at which the viral load of a person infected with HIV stabilises after a period of acute viremia is known as what?
Which other cell type of adaptive immunity is critical to reaching this point, and how does it destroy HIV-infected cells?
Viral set point
CD8 T-cells
perforins and granzymes
Why are innate natural killer cells different to adaptive CD8 T cells?
They don’t require prior activation; they have no memory (although there is growing evidence that they do); they are considered part of the innate immune system
Opportunistic infections typically ensue when the CD4 lymphocyte count drops below which critical threshold value?
200 cells/mm3
Features when looking at ELISA results?
Monoclonal antibody will be specific for a serotype if its the only one it has a significant absorbance to
A hybrid of serotypes can contain unique epitopes that doesn’t just consist of the ones from it combination of serotypes
What unique property of these immunoglobulin switch variants determines their isotype sub-class (IgG1, IgG2b, or IgG2a)?
Their heavy chain
Given your knowledge of antibody-antigen interactions and immune complex formation, explain briefly why the amounts of precipitated IgG1 and IgG2a decrease at the higher amounts of added cryptococcal polysaccharide?
Antibody-antigen EQUIVALENCE (not equilibrium) is needed for immune complex formation
A possible reason for the poorer polysaccharide precipitation and phagocytic index found with the IgG2b might be that a mutation in its F(ab) domain occurred during the in vitro class switching process. Why is this unlikely to be the case?
Because class-switching occurs in the strict order IgG1àIgG2bàIgG2a, and is irreversible. Therefore, if a mutation had occurred, the same poor precipitating ability would also be seen in the IgG2a.
Name a cell surface receptor and its ligand which are involved in fungal recognition?
Dectin-1 and b-glucans, Dectin-2 and mannans,
Surfactant Protein D (SP-D) is a soluble receptor which binds to a1-3-linked fucose on the surface of Cryptococcus neoformans. To which family of structurally related, carbohydrate-recognising proteins does SP-D and the related protein SP-A belong?
A third carbohydrate-recognising protein in this family is critical to the recognition of fungal pathogens. Name this third protein and its ligand?
Binding of this protein to its ligand activates the Complement Cascade. Which pathway of Complement does it activate?
Put in main deck
Collectins
Mannose-binding lectin (MBL) and mannose/mannan
Lectin pathway
How do T cells and B cells communicate without any physical contact?
Cytokines, chemokines
What is the protective component of the O-antigen antiserum?
Give 2 examples of the ways in which this protective component could be protecting against S. enterica infection?
What class of compounds is the O-antigen composed from?
Antibody
Agglutinating, opsonising, complement fixing, neutralising, ADCC, inflammation
A vaccine-based O-antigen alone would not be expected to induce good responses in children or induce good long-term protective immunity. How could these problems be resolved?
By generating a glycoconjugate; by linking the O-antigen to a protein.
What system is C3b a part of?
How is C3b generated and what other product would you expect to be generated?
What is are the main consequences of C3b deposition on the bacterial cell surface?
Complement
By proteolytic cleavage of C3; C3a
Opsonisation of the cells