Antibacterial Responses Flashcards
What is an infection?
Interaction between pathogen and host
What are the key steps in infection?
Entry of pathogen, invasion and colonisation of host tissue, evasion of immunity and tissue damage
Why can some bacteria not be cleared by immune system?
bacteria establishes latent or persistent infection
What is the first line of defense?
Innate / barriers
What are the 3 categories of innate first line of defense? + examples of each
Mechanical - flow of fluid (mucus, cilia)
Chemical - (sebum, acidity, lysozymes) + AMPs (defensins)
Microbiological - (normal flora)
What do defensins do?
Released into extracellular environment and kill microbes by penetrating microbial membranes and disrupting their integrity
Why is microbiota important apart from innate / barrier function?
Protect against unwanted immune response
What types of defensins are there?
alpha defesin and beta defensin
Which cell secrete alpha defensins?
Neutrophils and paneth cells
Which cells secrete beta defensins?
Broad range of epithelial cells esp in resp tract, skin and urogenital tract
What happens if initial barriers are crossed by pathogens?
Complement activation by microbial cell wall components
Complement is the PRR
When is the alternative pathway activated?
- specific PAMPs on bacteria cell walls (lipopolysaccharides)
Complement (PRR) recongises LPS in peptidoglycan to activate the pathway
When is the lectin pathway activated?
Complement (PRR) recognises mannose on surface of bacteria
When is the classical complement pathway activated?
Activated by antibodies and antigen binding
What is the indirect effect of complement pathways?
1) Induce inflammation, recruit inflammatory cells
2) Enhance phagocytosis via opsonisation
What is the direct effect of activated complement pathway?
Complement mediated cytolysis
Complement forms complex (polymersiation of complement) and punches holes in bacteria for lysis
Which type of microbes do complements usually work against?
Extracellular bacteria
How does complement make phagocytosis more efficient?
C3B (complement) decorates microbe targetting for phagocytosis
How does complement induce inflammation and how does this help in a bacterial infection?
C3B and C5A complement pathway induce inflammatory process which brings in more antibacterial neutrophils which destroy bacteria
Why do decorates microbes (with complement) enhance phagocytosis?
Phagocytes (macrophages) have lots of complement receptors (e.g. CR3 NOT TLRs) which detect the complement and takes up the bacteria indirectly (since receptor is specific to complement not bacteria allowing more efficient internalisation of bacteria for lysis
What are the 2 ways macrophages detect bacteria for phagocytosis?
TLRs (type of PRR) detect PAMPs (bacterial component directly) and takes up bacteria
Complement receptors detect complement (that has bound to bacteria) and takes up bacteria
Are PRRs complement receptors?
No since complement receptors do not detect PAMPs.
What receptors can be found on phagocytes?
PRRs - TLRs, scavenger receptors
Receptors for defensins
CR3, CR1 (complement receptors)
Where are TLRs found?
Phagocytic cells - on surface as well as intracellular (therefore can detect intracellular bacteria too)
What happens when PRR and PAMPs interact?
Phagocytosis (engulf) and cytokine production (initiation of inflammatory response)
How is an inflammatory response inititated?
Resident cells detect infection and produce chemokines and cytokines that increase endothelial permeability allowing circulating cell to infiltrate and be recruited to site of infection
Which cells infiltrate to area of infection in inflammation?
Neuttophils, monocytes and specific lymphocytes
What other chemical are released during an inflammatory response apart from chemokines and cytokines?
Local cells e.g. mast cells release histamine and prostaglandins
Neutrophils recruited early in inflammatory process. What do neutrophils do?
Phagocytosis and degranaultion of granules - intracellular killing of bacteria
Kill bacteria phagocytosing bacteria - NEUTROPHILS EXTRACELLULAR TRAPS (NETS
What is the role of antibodies?
Neutralise bacterial tocins
Trigger classical complement pathway by binding IgM to bacteria surface
Opsonisation - coat bacteria with antibody for phagocytosis
What response is antibodies involved in?
Humoral response
How do bacterial toxins disrupt normal function of host cells and how do antibodies do toxin neutralisation using this?
Bacterial toxin must bind to receptor to be internalised (endocytosis) with the receptor and disrupt function when the toxin is released from the receptor.
Antibodies bind to receptor to block toxin binding to receptor
What are the two methods of antibody opsonisation?
Only Antibodies coat pathogen entirely
or they can bind alongside complement also binding to pathogen aiding in uptake for phagocytosis (both antibody and complement can be recognised by phagocyte)
Step by step, explain the complement cascade?
Pentameric IgM bound to surface of bacterium binds to a complement component to initiate classical pathway of complement activation
Causes bacterial surface to be covered with C3B which faciliates phagocytosis
Why are only certain types of immunoglobulins involved in opsonisation for phagocytosis?
Diff Ig’s have diff anit-microbial properties
IgM in opsonisation with C3B complement
IgG for neutralisation of bacterial toxin
Why are only certain types of immunoglobulins involved in opsonisation for phagocytosis?
Diff Ig’s have diff anit-microbial properties
IgM in opsonisation with C3B complement
IgG for neutralisation of bacterial toxin
What events does an adaptive immune response lead to?
Inflammation and bacterial eradication (humoral by B cell and cellular by T cells)
Where do dendritic cells present antigens?
Extracellular bacteria taken up and dendritic cells travel to present them to T cells in secondary lymphoid organs e.g. lymph nodes
What are the 2 types of Th cells and what does each do? how does each come about
T cell activated and differentiates after encountering pathogen / antigen on APCs
Th1 - antibacterial response
Th2 - (indirect) activate B cells to produce antibodies
How do micobacterium tuberculosis hide in humans?
They hide inside macrophages
What is the purpose of cytokines in the innate response vs adaptive response?
Innate - Activate more immmune cell e.g NK cells
Adaptive - differentiate T cells into Th1 or Th2
What do CD4 helper T cells do?
Recognise peptide antigen complex and enhance phagocytosis of extracellular pathogens by activating macrophages
How do cells deal with intracellular bacteria?
Processed and presents antigen via MHC 2 molecules.
If helper T cells
