L8&9 : Immune responses against bacterial infections Flashcards
What factors affect the type of effector mechanism required in an immune response?
Type of pathogen, localisation, challenge and site of infection
Compare innate and adaptive immune mechanism
- innate are non specfic and fast acting, while adaptive are specific and take longer to develop
- adaptive exhxibits memory but innnate doesn’t
- innate uses physical barriers, component system, phagocytes and NK cells, while adaptive uses Abs and cell mediated immunty
What role do innate defence mechanisms have?
Act as first line of defence but are ineffective against many pathogen
What role do adaptive defence mechanisms have?
They enhance and focus innate defences, and are less easily evaded by pathogens
Name the types of specific response CD4+ cells
Th1,2 & 17
What is the function of Th1 cells?
Active against intracellular pathogens
- activates macrophages and stimulates CD8+ cells
What is the function of Th2 cells?
Active against extracellular pathogens
- supports Ab production, particularly class switching to IgE
- activates esinophils, basophils and mast cells
What is the function of Th17 cells?
Active against extracellular bacteria& fungi
- important in attracting inflammatory cells e.g. neutrophils
- induced early in infection
What innate responses can cell wall components (e.g. LPs, peptidoglycan) induce?
The binding to Toll-like receptors (TLR) on macrophages
- there are 10 TLR genes in humans: receptors recognise distinct molecular patterns on microbes, located on plasma membrane & endocytic vesicles
- NOD like receptors
The binding of PAMPs to TLRs can cause what responses?
- promotion of inflamaation
- promotion of dendritic maturation
- influence differentiation of T cells
- activation of B cells (TI-1 Ags)
Why is phagocytosis often effective against bacteria?
Bacteria may have protective capsules but can be opsonised by Ab/ componenet
What is the role of Abs in bacterial infection
- opsonisation: binds Fc receptors on phagocytes
- componenet activation: promotes inflammation via C3a + C5a, opsonise by binding C3b receptors on phagocytes & lysis of gram -ve organisms
- bind and neutralise toxins e.g. tetanus, diphtheria
- bind to surface structures to prevent mucosal adherance
What is a conseqeunce of defects in terminal complement componenets?
Can lead to susceptibility to Neisseria spp. and bacterial cell division becomes more vulnerable (can lead to cell death)
Gram +ve bacteria can be killed by lysis. True or false
False, gram -ve bacteria are killed by lysis
Some bacteria survive within phagocytes. True or false?
True
Give an example of how outcome of infection depends on the type of response
e. g. Myobacterium leprae
- tuberculoid leprosy: strong Th1 repsonse, few live bacteria, slow progessino, granuloma formation
- lepromatous leprosy: strong Th2 and Ab response, large no bacteria in macrophages, disseminated infection and can be fatal
What mechanisms are uesd to protect against extrcalleular pathogens and intracellular organisms respectively?
- Abs are imporant for extracellular pathogens e.g. s. pneumoniae
- T cell effector mechanisms are important for intracellular organisms e.g. mycobacterium
How do virus infected host cells use type-1 interferons (IFN alpha & beta)?
1- induces resistance to viral replication in all cells, by inducing Mx proteins, 2’-5’ linked adenosine ogliomer and the kinase PKR
2- increase MHC class I expression and Ag presentation in all cells
3- activates dendritic cells and macrophages and NK cells to kill virus infected cells
4- induces chemokines to recruit lymphocytes
IFN can induce the synthesis of what 2 molecules?
Protein kinase and 2’5’- oglioadrenylate synthetase
How can IFN lead to the degradation of viral mRNA?
IFN induces the synthesis of 2’5’ oglioadenylate synthetase
- leads to adenine trinucleotide being synthesised
- this activatees endonuclease
- viral mRNA degraded
How can IFN lead to the inhibition of protein synthesis?
IFN induces protein kinase
- leads to phosphorylation and inactivation of eIF-2
- this inhibits protein synthesis
At which point of infection can type I interferons be seen?
In early responses
What are type II interferons (IFN gamma) secreted by?
Activated T and NK cells
How do type II intereferons respond to infection?
- inhibit Th2 response (Ab)
- promotes Th1 (cell killing)
- recruits macrophaages (driving Th1 response)
rIFN alpha can be used to treat what diseases?
Hep B and C, and some cancers but side effects can be very severe
What is the function of NK cells in the immune response
- recognise structures on viral infected cellls & stressed in absence of Igs and MHC
- kills by extracellular mechanism: perforin and granzyme (potent) so work fast
How do NK cells distinguish between infected and uninfected cells?
- Activating receptors: recognise carbohydrate ligands, triggers killing
- Inhibitory receptors: recognises MHC class I molecules (no binding, only TCR can do this) and inhibits the activities & activation of these NK cells
How do some viruses make cells more susceptible to NK killing?
By reducing MHC expression
Explain methods of cell mediated specific immunity
- CD8+ cells (CTL): recognises viral peptide and MHC class I
- cytokines with anti viral activity: e.g. IFN gamma (class II, helps activate macrophages)
Explain the mechanisms by which CD8+ cells kill
- secretion of cytotoxic granulese e.g. perforin which polymerises in membrane, grnazymes (proteases) which enter cell
- Fas ligand on T cell interacts with Fas on target
What 2 processes/ interactinos lead to specific recognition?
Collision+ non specific adhesion
How does collision and non specific adhesion lead to specific recognition?
- redistributes cytoskeleton and cytoplasmic components of T cells
- leads to release of granules (vesicles) at site of cell contact
- this method is powerful and targeted, causing the polarised release of granules
How to CTLs kills cells?
- recognise and bind virus infected cell
- programs target for death, including DNA fragmentatino
- CTL migrates to new target
- target cell dies by apoptosis
How do CTLs secrete cytokines?
- inhibit viral replication
- upregulate MHC class I and II expression & Ag presentation
- increases macrophage phagocytosis of dead cells
- promotes NK cell killing activity
How do Abs respond to viral infections?
- Neutralises free virus (prevent entry into and spread between cells
can prevent spread within body (e.g. poliovirus) or protect mucosal surfaces against reinfection (e.g. flu) - Opsonise to increase phagocytosis
- Activate complement leading to lysis (enveloped virus)
Explain the role of Abs in cell mediated immunity of influenza
- infection induces Ab and CTL response
- Ab recognises viral haemagglutinin and neruaminidase
- high levels of CTL activity correlates with reduced viral stability
- epidemics arise due to new strains not recognised by Ab
How does HIV affect the immune system?
- attacks specific immune system
- targets CD4 T cells, macrophages and dendritic cells
- progressive developments of AIDS leads to opportunistic infections
How do Abs protect against parasites?
By opsonisation, complement lysis and ADCC (antibody dependent cell mediated cytotoxicity)
What response can some helminths (worms) evoke?
Can induce strong IgE Ab response which leads to the activation of mast cells (mediated inflammation), eosinophils and ADCC
What effector mechanisms are used for the malaria?
Different effector mechanisms are active at different stages
- sporozoite and merozoite may be susceptible at Ab
- Ab may also kill infected RBC
- CTL active against infected liver cells
