Unit 2: Advanced Concepts In Immunology Flashcards
what is the function of interferons (type 1, a/b)?
- makes cells more resistant to replication
- enhances antigen presentation
- increased degradation of viral mRNA
- reduction of viral protein synthesis
- increased antigen presentation
what is the function of virus neutralising antibody?
virus neutrilisation in extracellular fluid
what is the function of CD8+ killer T cells?
destruction of virus-infected cells during replication phase
how can viruses avoid virus neutrilising antibodies?
- formation of syncytium
continual transmission without ever going into extracellular fluid via viral fusion protein to surrounding uninfected cells
= large multinucleated cells - genome integration into host (retrovirus)
- malignant proliferation
Describe how Ebola uses antigen decoys to evade the immune system
- decoy similar to structural protein, but soluble
- secreted on mass to saturate antibody binding sites
- v.particle released, but antibody already complexed
describe how CD8+ killer T cells cause infected cell death
- detect MHCI presentation on infected cell
- degranulate = release perforin + granzymes
- FasL + TNF = cytotoxic cytokines act on death receptors
- trigger caspase cascade = apoptosis
give some examples of immune-privileged sites
- CNS
- eyes
- testes
what is recrudescence?
reactivation of latent infection to become fulminant again
what are some triggers for recrudescence?
- stress (cortisol = immunosuppressive)
- medication
- lowered immunity
some bacterial capsules are made from components commonly found in the host - what is the advantage of this?
molecular mimicry - immune system evasion
how does a bacterial capsule interfere with the complement cascade?
inhibit correct binding of serum proteins (for activation of complement) via C3b pathway
inhibits phagocytosis
what do adhesin proteins A and M target as a phagocytosis evasion strategy?
Fc portion of IgG
interferes with IgG binding - binds Fc region instead of binding domain
how are some bacteria able to survive within a phagosome?
- production of detoxifying components
- catalase production
what is an AMP?
antimicrobial peptides
- multiple cysteine residues
how can bacteria evade AMPs?
- presence of a capsule
- LPS layer in G-ve (LPS binds to AMP, prevents binding with membrane target)
how can bacteria evade the action of lysozyme?
can alter the chemistry of peptidoglycan = deacetylation at O residue
what is horizontal gene transfer?
the ability to require genetic material from eg the environment
= genetic variation
what is phase variation?
the switching of protein expression in bacteria to an off phase (reversible)
what are the mechanisms of phase variation?
- hypermutable sequences eg poly G-tracts
- recombination
- promotor inversions
- epigenetic mechanisms eg methylation
what is the process which causes phase variation occurs via hypermutable sequences
- tract length of G9 = full length transcription product (ON)
- insertion mutation = G10/G11 = often early stop codon (gene OFF state)
- more insertions (G12) = gene back to ON
what genes contribute to capsule synthesis via addition of sialic acid?
- cssA
- cssC
what are DAMPs?
damage-associated molecular patterns
give some examples of prokaryotic PAMPs
- flagellin
- peptidoglycan
- LPS
- bacterial DNA
- lipoteichoic acid
give some examples of DAMPs
- ATP (found in ECF after death)
- mitochondrial DNA
- heat shock proteins
- IL-1a
last two induced by dying cells = alert
what are the 4 types of PRRs?
- vesicular
- membrane-associated
- cytoplasmic
- soluble
how does the innate immune system detect viral infection?
- the presence of dsRNA or DNA in cytoplasm
- TLRs expressed on cell surface/ intracellular vesicles
- cytoplasmic helicases detect v.nucleic acid (RIG-1…)
what are the molecules which recognise bacteria (phagocytic cells)?
- TLRs
- NOD-like receptors
- C-type lectins
- complement C3 protein mannose-binding lectin C-reactive protein
what are some important TLRs (extracellular) for bacteria recognition? what do they bind to?
- TLR-2 = peptidoglycan + zymosan
- TLR-4 = LPS + HSP60
- TLR-5 = flagellin
- TLR-9 = CpG DNA
what are some NOD proteins (intracellular) for bacteria recognition? what do they bind to?
- NOD1 = iE-DAP (from LPS)
- NOD2 = MDP (from peptidoglycan)
what are C-type lectins sensors for?
foreign carbohydrates
what does TLR-4 associate with in order to work?
CD14 (marker of macrophages)
what are the two TLR-2 heterodimers? what does this allow for?
triacylated lipopeptides
diacylated lipopeptides - detects PAMPs of g+ve bacteria + yeast
what do keratinocytes express in response to infection? what are they adapted to recognising?
- influx of B-defensins + cathelicidin = anti-microbial
- expression of IL-1a + IL-8
g+ve bacteria and yeast
what do enterocytes express in response to infection? what are they adapted to recognising?
- influx of B-defensins + cathelicidin
- internal production of DAMPs + chemokines
- expression of IL-1a + IL-8
- have TLR-4 and TLR-5
- g-ve bacteria
what are b-defensins? what is their function?
- small cationic peptides
- different anti-microbial properties
- disrupt microbial membrane and/or interfere with intracellular functions
what are the b-defensin genes in humans and what are their functions?
- HBD1 = expressed by human keratinocytes
- HBD2-4 = inducible in keratinocytes by PAMPs and pro-inflammatory cytokines
what is CAMP?
cathelicidin antimicrobial peptide
what mediates the inflammatory response and what are does this cause?
- IL-1b, IL-6, TNF-a
- vasodilation
- increased capillary permeability
- influx of white blood cells
how does the innate immune response influence T cell activation?
- PRRs induce cytokine expression = influence of T cell differentiation
- PRRs induce different cytokine profiles = influence CD4 T cell differentiation
what are the subsets of B cells and what are their generic population size within the spleen?
- B-1 cells (a+b = PRIMITIVE) = 2%, <1%
- B-2 cells (marginal zone, follicular = GENERAL) = 15%, >70%
- regulatory B cells = 1%
where in the body would you find primitive B cells?
pleura and peritoneum
what is central tolerance to B cells?
recognition to self-protein = cell death
- IgM first expressed on immature B cells, if encounter target antigen that can crosslink their sIgM = programmed death = no longer in repertoire
what two signals are required for B cell activation?
- B cell receptor binding (antibody)
- T cell help = TD antigens (thymus-dependent)
describe the antibody response against a virus
- B cell virus binding through v.coat protein
- particle internalised and degraded
- peptides presented to T cell = B cell activation
- B cell produces antibody to v.coat protein
describe the antibody response against a bacterial component
- B cell binds b.polysaccharide epitope
- antigen internalised and processed
- peptides from protein presented to T cell
- antibody produced against polysaccharide antigen
what signals are required to activate T-independent antigens?
only binding to receptor, second signal can be delivered by antigen
ONLY produces IgM - no class switching without T cell help
what type of cells produce antibodies?
plasma cells
which T cell subset is involved in B cell activation?
CD4 Th2
what processes generate high affinity Ig’s?
- somatic mutation = in V region of activated B cells = increased affinity
- class (isotype) switching = requires cell-cell contact and cytokine production)
what is the function of regulatory B (Breg) cells?
- immunosuppressive - immunological tolerance
- produce IL-10, IL-35 + TGF-B
- suppression of immunopathology via prevention of pathogenic T cell expansion
where is the complementary determinant region on antibodies?
found in variable region
what is the function of these T cells and what pathogens do they target?:
- CD8 cytotoxic T cell
- CD4 Th1 cell
- CD4 Th2 cell
- CD4 Th17 cell
- CD4 regulatory T cells
- kill infected cells; viruses + some intracellular bacteria
- activate infected macrophages + help B cell antibody production; macrophage-vesicle microbes + extracellular bacteria
- help B cell antibody production (switch to IgE); helminths
- increase neutrophil response; extracellular bacteria
- T cell response suppression; N/A
what is the function of CTLA-4? what would happen if cells didn’t have this?
- upregulated after activation = negative proliferation signal (not expressed when inactivated)
- cells would keep proliferating (bad)
what APC activates naive T lymphocytes (the best)?
dendritic cells
what is the co-stimulatory molecule on T cells?
CD28
which cytokines are responsible for the differentiation of naive T cells into Th17?
IL-6 and TGF-B - act via RORyT = key transcription factor
what is the primary mediator of macrophage activation to kill intracellular pathogens?
IFN-y
what is the primary mediator of B cell activation and class switching?
IL-4
