Antibacterial responses Flashcards
What are some features of 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
Do all bacteria cause disease?
Bacteria do not always cause disease
The intestine in a healthy adult contains about 1014 essential bacteria with about another 1012 on the skin
Microbiota is a mechanism of protection to infection both ecological and immunological
What are some general features of immunity to bacteria?
Defense 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 do anti-bacterial peptides do?
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.
If happens if initial barriers are crossed?
Complement activation by microbial cell wall components
Complement being a PRR
What is the complement system?
Key effector function of the humoral response.
Serum and cell surface proteins(normally secreted by the liver) that interact with one another to generate products that eliminate extracellular bacteria
3 main pathways to the complement system:
The classical pathway
The lectin pathway
The alternative pathway
all sort of come together, leading to c3 and c5 convertases which directly and indirectly lead to various effects (inflammation, lysis, opsonisation)
What do pattern recognition receptors (PRRs) and PAMPs lead to?
Phagocytosis and the production of cytokines:
PAMP binding by PRRs activates the phagocyte
Phagocyte ingests microbes, enlarges and increases metabolic activity
Activated phagocytes elevate antimicrobial activity
If infection is detected through TLRs, pro-inflammatory cytokines(eg IL1 Il6 and Tnf-alpha) and chemokines are produced, leading to the initiation of an inflammatory response.
What do neutrophils do?
Neutrophils perform phagocytosis.
Neutrophils perform 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)
What is the function of the antibodies in the humoral response?
Neutralise bacterial toxins
Trigger classical complement pathway by binding of IgM to the bacterial cell surface
Opsonisation; coating of bacteria with antibody thereby aiding phagocytosis
What is involved in the triggering of the complement cascade?
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.
What does the adaptive immune response lead to?
inflammation and bacteria eradication
What is the role of dendritic cells in the process of antigen uptake and presentation?
Extracellular bacteria is rapidly detected by dendritic cells locally present in the tissues, which will detect PAMPs through TLRs for example. Dendritic cells will then migrate after taking up/activating the antigen to take and present to the T cells.
The specific T cells are then activated and a cellular response can be induced
How do helper T cells enhance phagocytosis of extracellular pathogens?
Helper T cells enhance phagocytosis of extracellular pathogens by activating macrophages
The MHC class II pathway presents bacterial antigens derived from extracellular infections to helper CD4 T cells
- Macrophage engulfs and degrades bacterium, producing peptides.
- Bacterial peptides are bound by MHC Class II in vesicles.
- Bound peptides are transported by MHC Class II to the cell surface.
- Helper T cell recognises complex of peptide antigen with MHC Class II and activates macrophage.
Overall, what is involved in innate immunity and adaptive immunity?
The innate immune response to bacterial infection: Complement Pattern recognition of bacteria Phagocytosis Opsonisation Cytokine secretion Inflammation
The adaptive immune response to bacterial infection
CD4+ and CD8+ T cells
Antibodies
