8. Haemophilus

6 typable strains of H. influenzae

Encapsulated strains a-f

Unencapsulated H. influenzae

Non-typable H. influenzae (NTHi)

What type of disease is caused by unencapsulated strains

Less invasive 

H. influenzae endotoxin

Lipooligosaccharide 

H. influenzae LOS

(lipooligosaccharide) is a variation of typical LPS

What part of LPS and LOS is the actual toxin

the lipid A component

In H. influenzae, lipid A is a PAMP for ____

TLR4

Since lipid A is a PAMP for TLR4, what does it do

Activates pro-inflammatory cytokines

H. influenzae adhesins bind to

host ECM components such as fibronectin and collagen

H. influenzae adhesins 

HMW1 and HMW2
Hap
Protein E (PE) and Protein F (PF) 

HMW1 and HMW2

adhesins that bond to host proteoglycans

H. influenzae Hia

autotransporter ahdesin that binds to host fibronectin

H. influenzae Hap 

Autotransporter adhesin that binds to host epithelial cells bu binding to laminin, fibronectin, and collagen 

H. influenzae protein E and protein F (PE and PF) 

ABC transporter adhesins that bind to laminin and vitronectin 

H influenzae pili

adhere to epithelial cells of nasopharynx

H. influenzae PilA

pilus tip protein that binds to ICAMS and mucin on epithelial cells

Phase variation  

reversible, high frequncy switching of gene expression 

In H. influenzae phase variation is mediated by

tandem DNA repeats in genes rhat express surface virulence proteins

Tandem repeat

short sequnce of DNA that is repeated numerous times (2-20 times)

How do tandem repeats allow for phase variation 

they lead to transcriptional slippage which causes insertions or deletions in the repeat regions, thereby altering gene expression.

Many of the biosyntheic genes of H. influenzae LOS are ____

Phase variable to change after expsure to human serum

Both HMW1-2 and Hia are

controlled by phase variation and can be downregulated when proteins are recognized by immune system

IgA

found in mucosal sites of the body 

H. influenzae IgA1 protease

cleaves human IgA to destroy protection from mucosal barrier

Outer membrane vesicles are found in which type of bacteria

gram negative

When H. influenzae releases OMVs, they act as decoys for what 

complement mediated killing by host immune system 

H. influenzae OMVs stimulate ___

excessive cytokine release by host, causing host cell damage and increased invasion

First choice antibiotics against H. influenzae

beta lactams, like penicillins and cephalosporins

How does H. influenzae decrease sensitivity to beta lactams 

modify cell permeability so antibiotic no longer has cell wall target 

HOw can H. influenzae modify cell permeability

via decreased porins and genetically modify penicillin binding protein (via point
mutations)

What is often used to treat H. influenzae in adults

Fluoroquinolines

How do fluoroquinolines work 

target DNA gyrase and topoisomerase —→ impeding DNA replication 

Fluoroquinoline resistance

mutations in topoisomerase and gyrase

Complement immune system

refers to a series of proteins in the immune system that enhance the ability of antibodies and phagocytic cells to clear pathogens from an organism.

Activation of complement leads to 

opsonization 
Inflammation 
Lysis 

What triggers the alternative pathway of complement activation?

Spontaneous hydrolysis of C3, leading to deposition of C3b on cells.

What forms the C3 convertase in the alternative pathway?

C3b binds with Bb to form C3bBb, which amplifies the immune response.

How does the body prevent complement activation on its own cells?

Factor H (FH) binds to self markers and blocks further C3b activation.

What does Factor H do to C3 convertase?

It dissociates C3b from Bb, preventing formation of more C3bBb.

How does Haemophilus influenzae evade the immune system?

It binds Factor H to its surface to block complement activation.

Blood brain barrier 

blood vessels that vascularize the CNS, which tightly regulate movement of ions, molecules, and cells 

How to cross blood brain barrier

Transcellular

Paracellular
Infected phagocyte (trojan horse)

Transcellular route

is a mechanism where substances cross the blood-brain barrier through the cells themselves, rather than between them, allowing selective transport.

Paracellular route

is a mechanism where substances cross the blood-brain barrier by moving between adjacent cells, typically allowing small molecules or ions to pass freely.

Infected phagocyte route

is a transport mechanism where infected phagocytes hijack the immune system to traverse the blood-brain barrier, effectively acting as a Trojan horse for pathogens.

How does H. influenzae cross the BBB

transcellular or paracellular route