physical and chemical barriers

physical barrier

Epithelial cells lining the internal and external surfaces of the body along with phagocytes beneath the epithelial surfaces

chemical barriers

• antimicrobial enzymes

• antimicrobial peptides

• the compliment system

induced responses of innate immunity

Activation of innate immune cells by pattern recognition receptor (PRR) that recognize pathogen associated molecular patterns (PAMPs)

proteins with enzymatic activity

• Lysozymes (Glycosidase activity against bacterial cell wall)

• Phospholipase A₂ (hydrolyzes phospholipids in the cell membrane bacteria

non-enzymatic peptides

short cationic peptides with a common amphipathic structure - a positively charged region separated from a hydrophobic region

• defensins

• cathelicidins

• histatins

the compliment proteins

a collection of soluble heat liable proteins produced by the liver, and are present in the blood and other bodily fluids

Peptidoglycan of bacterial cell wall, how do lysozymes digest it?

polymer of alternating residues β-(1, 4) linked N-acetylglucosamine and N-acetylemuramice acid

lysozyme cleaves β-(1, 4) linkage, creates a defect in the peptidoglycan layer and exposes the underlying cell membrane to other microbial agents

what activates defensins, cathelicidins, and histatins?

activated by proteolysis, so they can release an amphipathic antimicrobial peptide

how defensins disrupt the cell membranes of microbes

amphipathic structure allows it to interact with the lipid bylayer - inserts itself and forms a pore to mess up membrane integrity

the compliment system

• a collection of more than 30 soluble heat-liable proteins in the blood and other fluids 

• produced by the liver

• many are proteases produced in the inactive form and and cleave and activate each other in the presence of a pathogen

• also includes compliment receptors and compliment-regulatory proteins 

3 pathways for compliment activation

• classical pathway - antibody triggered

• Alternative pathway - activated by pathogen alone

• lectin pathway - activated by lectin-type proteins

all pathways generate a C3 convertase, which cleaves C3, leaving C3b bound to the microbial surface and releases C3a

effector pathways AFTER compliment activation

• inflammation - C3a (intermediate activity), C4a 
  (weak activity), C5a (high activity)

• phagocytosis - involves C3b and C5a

• membrane attack - involves C5b. C6, C7, C8, and C9

Opsonization

the process of coating a pathogen with antibodies and/or compliment proteins so that it can be more readily taken up by phagocytic cells

Inflammation induced by compliment proteins

• small compliment-cleavage products act on blood vessels to increase vascular permeability and cell-adhesion molecules

• this increases fluid leakage from blood vessels and extravasation of immunoglobulinand compliment molecules

• migration of macrophages, polymorphonuclear leukocytes, and lymphocytes is increased. microbicidal activity increased

phagocytosis of opsonized microorganisms

• bacterium is coated with C3b

• when only C3b binds to CR1, bacteria are not phagocytosed 

• C5a can activate macrophages to phagocytose via CR1

membrane attack complex

terminal compliment proteins polymerize to form pores in the membranes that can kill certain pathogens