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