Humoral arm of innate immune response

Lines of innate immune system defence

• Physical and chemical barriers

• Cell intrinsic responses

• Specialised proteins and cells

Physical and chemical barriers

• thick layer of dead keratins cells

• Tight junctions between epi cells

• Acidic stomach

• Mucus layers

Cell intrinsic responses

• pathogen induced phagocytosis

• Degradation of dsDNA

Mucus layers overview

• On moist epithelial surfaces

• Protects against microbial, mechanical and chemical insults

• Made from secreted mucin and other glycoproteins

• Slippery, hard for pathogens to attach to the epithelia underneath

• Contains defensins

Mucin

• has a cytoplasmic and transmembrane region

• O linked glycans attach to the core protein

Defensins

• small +ve anti microbial peptides

• Hydrophobic and amphipathic helical domains

• +ve charges lie on one face of coil, hydrophobic residues on the other

• Wide antimicrobial activity

• Multiple types in multiple classes, large repertoire of targets

• Non specific action, pathogens struggle to acquire resistance

How defensins work

• hydrophobic of amphipathic domains may enter core of pathogen lipid membrane , destabilising it

• Leads to cell lysis

• +ve charges may interact w -ve nucleic acids in pathogens

Why defensins don’t lyse our epi surfaces

• more active of membranes not containing cholesterol

PAMPs Acronym

• pathogen associate molecular patterns

PAMPs description

• also called pathogen/microbe associated immunostimulants

• Common to many pathogens, absent in host

• Allow innate immune system to recognise non self material which breaches epi barriers

Classes of PAMP

• fMet - used for initiating bacterial translation

• PG

• Flagella

• LSP

PRR acronym

• pattern recognition receptors

PRRs overview

• blood receptors - components of complement system

• Perform direct killing.

• TLR - alarm system

Lectin pathway

• mannose and fucose binging proteins

Complement

• 20 soluble proteins activated sequentially upon infection

Stage 1 complement

• early components are pro enzymes , activate the next member in line via cleavage

• Results in amplified proteolytic cascade

Pathways stim complement

• lectin pathway

• Alternative pathway (pathogen surfaces)

Complement stage 2

• pivotal proteolytic - cleaves C3 into C3a and C3b

C3a

• calls for hep

• Attracts phagocytes and lymphocytes

• Stim inflammation

C3b

• binds covalently to pathogens plasma membrane

Stage3 complement

• pathogen bound C3b stimulates local cascade of reactions at the membrane (C5-8)

Stage 4 complement

• C9 inserts into membrane

• C9 multimers makes a pore in the membrane - membrane attack complex

Stage 5 complement

• pathogen lysis

Toll

• Drosophila trans membrane protein

• Large extracellular domain w repeating motifs , versatile binding motifs for variety of proteins

• Binding sends signal to nucleus that results in expression of defensins

Toll like receptor

• on CM of epi cells, macrophages, dendritic cells and neutrophils

• Binding sends signals to nucleus, results in transcription of many genes , promote inflammation (+ interferon response

Ancient immune system components

• defensins and TLR

• Involved in innate immunity in all multicellular organisms

• Pre date the ancestral

Neisseria gonorrhoeae

• gram -v diplococcus

• Causative agent of gonorrhoea

• Requires chocolate agar to grow in lab

Gonorrhoea Symptoms

• Common to be asymptomatic

• Discharge

• Issues if newborns exposed

Prevalence of gonorrhoea

• 2nd most common bacterial STI

• Never reached the healthy people target

• Most common in early - mid adult

• More likely for man to infect female than vice versa (transmission wise)

Evasion of innate immune system

• presence of LOS instead of LPS

• Host derived sialic acid used to sialylate pathogen LOS

• Makes pathogen less invasive it more resistant to bactericidal serum

• Because human cells has sialylated glycoproteins - disguised as human cells