5 Defence Systems of pathogens

Antibody opsonization is a process by which a pathogen is marked for phagocytosis

Host defence

Cell wall-anchored proteins

Immunomodulators

Toxins

Nucleases

• Produces toxins which inhibit mucus removal

• Toxin known as Tracheal cytotoxin (TCT)

• Toxin actually a particular fragment that is released from the cell wall during growth

  • Paralyses mucociliary escalator and also causes loss of ciliated epithelial cells → allows bacteria to colonize the epithelium

A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs.

• These proteins kill bacteria by insertion of the cationic (positively charged) peptides into microbial membranes

• Found at mucosal surfaces and within granules found in phagocytic cells (neutrophils)

1. defensins

2. cathelicidins

3. thrombocidins - from platelets

1. Modification of membrane charge

   • makes less susceptible to binding of cationic peptides

2. Direct destruction of peptides (defensins)

   • Production of Staphylokinase

     • Binds and forms complex to neutralise activity

   • Streptococcus pyogenes

     • M1 protein sequesters peptides and prevents activity

3. Efflux pump

In Yersinia

(a) acidification of the cytoplasm making Cationic antimicrobial peptides (CAMPs) less effective

(b) active pumping of peptides from cell

RosAB efflux pump

• pump acts as a potassium antiporter, using a potassium gradient that pumps K+ ions into the cell as it pumps out harmful CAMPs

• rosAB deletion mutants more sensitive than wild-type to the CAMPs polymyxin B, cecropin P1

4. Bacterial biofilms are a consortium of surface-attached bacterial cells that are embedded in a matrix composed mainly of extracellular proteins, extracellular DNA and exopolysaccharides (EPS)

• Bacteria in biofilms exhibit higher resistance (up to 1000-fold) to AMPs (and antibiotics) than planktonic bacteria

• Increased resistance is partly mediated via decreased penetration of AMPs through the matrix

1. Modification of membrane charge

2. Direct destruction of peptides

3. Removal of AMPs

4. Resistance to AMPs – biofilm formation

Heme is a coordination complex of iron and a porphyrin ligand that is biosynthesized in the bone marrow and the liver.

Secretory Immunoglobulin A

(a) Inhibition of pathogen adhesion

(b) Neutralisation of intracellular viral replication

(c) Limit inflammation - blocking activation through NF-κB

(d) Recycling/removal of antigen/bacteria

Bacteria produce various glycosilidases

• sIgA is heavily glycosylated

• Cleavage of sugars make antibody sensitive to proteases

IgA1 proteases produced by several bacteria

• Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

• cleave IgA1 H chain near chain region

Neutrophil extracellular traps (NETs) are networks of DNA-rich fibers that neutrophils form to bind and kill extracellular pathogens.

degrades DNA backbone and enables liberation of bacteria from NETs

acidic polysaccharides

Hemolysis is the rupturing of red blood cells and the release of their contents into surrounding fluid.

An exotoxin is a toxin secreted by bacteria that can cause damage to the host cells or disrupt normal cellular metabolism.

S. aureus and S. pyogenes produce

S. pyogenes causes streptococcal toxic shock syndrome and necrotising fasciitis

(1) An outer capsule prevents complement activation

(2) An outer surface can be configured so that complement receptors on phagocytes cannot obtain access to fixed C3b

(3) Surface structures can be expressed that divert attachment of the lytic complex (MAC) from the cell membrane

(4) Membrane -bound enzyme can degrade fixed complement or cause it to be shed

(5) Complement inhibitors can be captured onto the surface

(6) Direct inhibition pf C3 and C5 convertases blocks complement activation

• Bacteria possess antigenic determinants that are very similar or identical to normal host cell components

• This phenome known as molecular mimicry occurs in a wide variety of bacteria

• However, molecular mimicry may be the initiating step in autoimmune diseases

  • e.g. M protein of S. pyogenes elicits autoantibodies that cross-react with heart myosin leading to heart damage

  • rheumatic heart disease

• Mechanism by which bacteria alters its surface proteins in order to avoid host immune responses

• Bacteria will change a variety of cell surface molecules that can be determined by specific antibodies

• A single strain may express several antigenic variants of a cellular component

• The genetic information for predicting a family of antigenic variants is available in the cell, but only one variant is expressed at a given time

absence of the normal immune response to a particular antigen

• poor recognition

• desensitization of immune responses

• inhibition of secondary immune signals