Antibacterial Responses Flashcards
What are the features of a bacterial infection?
In general, bacterial pathogens live and replicate in extracellular spaces with exceptions
Several of the most acute and dangerous bacterial diseases are caused not by the bacteria themselves but by the toxins they produce
Infection is an interaction between the pathogen and the host
Key steps in infection: entry, invasion and colonisation of host tissue, evasion of immunity, tissue damage
What are the general features of immunity to bacteria?
Defence mechanisms against microbes comprise both the innate and the adaptive immune system
The immune system responds in specialised and different ways to different types of bacteria
The pathogenicity and survival of the bacteria is critically influenced by the ability to evade the effector mechanism of immunity
Some bacteria establish latent or persistent infection and the immune system does not clear the microbe
In many cases tissue damage is associated to immunity not to infection
Defects in the immune system associate to susceptibility.
What are ABPs?
Anti-microbial peptides capable of killing by penetrating microbial membranes thus disrupting their integrity.
They are active against bacteria, fungi and many enveloped and non-enveloped viruses.
There are two types: 𝛂-defensins and β-defensins.
𝛂-defensins are secreted mainly by neutrophils and by Paneth cells
β-defensins are secreted by a broad range of epithelial cells, in particular, those in the respiratory tract, the skin and the urogenital tract.
What happens if bacteria make it past the initial defenses?
Complement activation by microbial cell wall components
Complement being a set of PRRs
Can recognise peptidoglycan or LPS and activate the alternative pathway of complement
Should a bacteria have mannose on the cell walls, the mannose-binding lectin will detect it and activate the lectin complement pathway
What happens if complement is activated?
A microbe has been detected by the molecules C3b and binds to it
It targets the microbe through opsonisation for a more efficient phagocytosis
The tagging of PAMPs through the binding of molecules like C3b can, via C3a and C5a, induce or contribute to an inflammatory response and help bring in antibacterial neutrophil
The last function is the polymerisation of the membrane attack complex
- This is a group of proteins that come together to form cylinders that punch holes in the membranes of bacteria, lysing the bacteria
What are the role of complement receptors in phagocytosis?
Macrophages have high levels of expression of complement receptors
The complement molecule binds to the microbe and then binds to the receptor on the macrophage
Macrophages can also detect a PAMP and that signal will lead to the production of cytokines but needs the complement molecules to phagocytose it?
What are the different types of TLRs?
We have 6 different types of extracellular TLRs detecting extracellular bacteria and 4 intracellular ones able to detect intracellular bacterial infections
The most important ones are peptidoglycan detected by TLR-2 and LPS by TLR-4
What happens in the tissues when inflammation begins?
A resident cell produces pro-inflammatory cytokines and chemokines
These change the characteristics of the endothelium, allowing for circulating cells, leukocytes to go to the site of infection
The first cells are always neutrophils that have potent antibacterial responses
The process of inflammation is then followed by the infiltration of monocytes and specific lymphocytes
Some local cells can contribute to the process such as mast cells releasing histamine and prostaglandins
How are bacteria killed after inflammation?
Phagocytosis and degranulation of granules- intracellular killing of bacteria
Phagocytosis and oxidative burst kills the bacteria
Neutrophils can also kill bacteria phagocytosing bacteria - Neutrophils Extracellular Traps (NETS)
They burst out, leaving behinds a jumble of DNA and proteins but blocking the bacteria from moving
Early on recruited to the lung
What are the functions of antibodies against bacteria?
Neutralise bacterial toxins
Trigger classical complement pathway by binding of IgM to the bacterial cell surface
Induce opsonisation; coating of bacteria with antibody thereby aiding phagocytosis
How do antibodies neutralise toxins?
- Toxin binds to cellular receptor
- Endocytosis of toxin; receptor complexes
- Dissociation of toxin to release active chain which poisons cell
- Antibody protects cell by blocking binding of toxin
Many bacteria secrete protein toxins that cause disease by disrupting the normal function of host cells
In order to do this a bacterial toxin must bind to a receptor
Thus, antibodies that bind to that receptor block the function of the toxin
How does IgM activate the complement system?
IgM bound to the surface of a bacterium binds to a complement component that initiates the classical pathway of complement activation.
As a consequence of this the bacterial cell surface is coated in C3b facilitating its phagocytosis.
Similarly IgG can also do that through its binding to C1q
How does the adaptive immune response lead to bacterial eradication?
Cellular response revolves more around the CD4+ helper T cells releasing IL-17, TNF, cytokines
An important chemical it releases is Interferon gamma which activates macrophages leading to phagocytosis and bacterial killing
