Bacterial Strategies For Host Damage Flashcards
What are bacterial toxins
Bacterial toxins are proteins produced by certain species of bacteria that can cause damage to host cells and tissues, leading to a range of pathological effects.
What are bacterial toxins made of
They are lipid components of the cell wall -endotoxin
Secreted proteins and peptides -exotoxins
2 types of bacterial toxins
Endotoxin
Exotoxin
What is endotoxin often referring to
The lipid portion of the lipopolysaccharide molecule
Chemistry of lipopolysaccharide molecule
Lipid A - bottom of LPS (attached to outer membrane)
It has endotoxic activity
Middle part is made up of inner and outer core (inner core closer to lipid A or outer membrane)
Polysaccharide O chain at top of LPS
- causes activation of host complement
-serological specificity
How can gram negative bacteria have different serotypes
Through variation of their polysaccharide O chain
What happens when LPS (on gram negative bacteria) interact with host macrophages
First, the LPS binds to toll-like receptor 4 (TLR4) on the surface of the macrophage. This interaction triggers a signaling cascade within the macrophage, leading to the activation of various transcription factors, including nuclear factor kappa B (NF-kB).
Activation of NF-kB leads to the production and release of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). These cytokines recruit other immune cells to the site of infection and activate them to eliminate the bacteria.
In addition to cytokine production, LPS also induces the expression of co-stimulatory molecules, such as CD80 and CD86, on the surface of macrophages. These molecules play a critical role in activating T cells, which are important for coordinating the immune response to the infection.
Overall, the interaction between LPS on gram-negative bacteria and host macrophages leads to the activation of the innate immune system and the production of pro-inflammatory cytokines and co-stimulatory molecules, ultimately resulting in the elimination of the bacteria.
Types of protein toxins
Type 1 - do not enter host cell membrane ~ superantigens
Type 2 - disrupt eukaryotic cell membrane ~ phospholipase
Type 3 - A-B toxins act intracellularly ~ B region bonds to the eukaryotic cell by recognising a receptor ~ A portion enters cytoplasm
What toxin is involved in toxic shock syndrome
Type 1/superantigens - causes overstimulation of immune system to exert its effect
Types of A-B toxins
Single chain peptides with multiple domains, such as DT and the Botulinum NTs
Multi subunit complexes such as cholera toxin and anthrax toxins
How do superantigens work
Interfere normal antigen presentation
Superantigens cause the inappropriate stimulation of T cells
Antigen presenting cells will have a peptide in the class 2 MHC which isn’t necessarily T cell specific but the superantigens will cause the TCR to bind to it, stimulating the T cell
Over stimulation of T cells
Overproduction of inflammatory cytokines (tumour necrosis alpha [TNF-a])
Impacts circulatory system, high fever, organ damage
Examples of superantigens
Gram + cocci
S.aureus
Staphylococci enterotoxins
How do type 2 toxins work
They are pore forming toxins
Pore forming toxin molecules bind to surface if host cell membrane and polymerise
Polymerised toxin inserts into cell membrane creating a channel
Disrupts osmotic balance of the cell
Examples of pore forming toxins
Streptococcus pyogenes
Produces
Streptolysin O and S
Thèse lyse RBCs by forming pores in the membrane
Type 2 toxins don’t just have to be pore forming, they can also be
Enzymes
Which knock of the phosphate head from bilayer
Destabilising the membrane
Disregulates osmotic balance
