3. innate & acquired immunity

innate immunity refers to _____

• various physical, chemical, and cellular barriers that represent the first line of defense against infectious disease

• uses proteins encoded in the germline (elements an individual is born with)

features of innate immunity

• preformed or rapidly induced on short notice

• no memory: NOT enhanced by prior exposure; same response each time

• broad specificity → stimulated by structures that are common to groups of related microbes

  • LPS (gram - )

  • peptidoglycan (gram +)

features of acquired/adaptive immunity

• specificity

• memory

• diversity

• clonal expansion/contraction

• specialization

• non-reactivity to self

mechanisms/components of innate immunity

• anatomic/physical barriers

• physiologic & chemical barriers

• cellular barriers

• inflammatory barriers

what are epithelial barriers?

• cells held together by tight junctions

  • skin

  • mucous membranes — conjunctiva, GI, respiratory, and urogenital tracts

• external/first lines of defense

how do mucous membranes protect against microbes?

• secretions → saliva, tears, urine, mucus

  • wash away/inhibit growth/trap microbes

• cilia → muco-ciliary escalator

• peristalsis in GI tract, coughing, sneezing removes microbes

  • gut stasis leads to microbial growth and infection

functions of epithelial barrier

• physical barrier to infection

• epithelial cells produce & secrete peptides antibiotics

• intraepithelial lymphocytes kill microbes

defensins and cathalicidins are examples of what?

peptide antibiotics produced and secreted by epithelial cells

physiological/chemical barriers

• fever

• pH → stomach, vagina, skin

• normal microflora → GI tract and skin

• chemical mediators

  • defensins (secreted by epithelia)

  • hydrolytic enzymes of saliva

  • lysozyme in tears, sweat, and saliva

  • surfactant has antimicrobial properties

interferons

interfere with viral infection

anti-viral actions of type I interferons

• paracrine signaling → virally-infected cell secretes interferons → induces antiviral state in nearby cells

• activates NK cells

• promotes CD8+ T cells/cytotoxic T lymphocytes (CTLs)

highly conserved (maintained through evolution)

steps in phagocytosis

1. adherence and opsonization

2. ingestion

3. destruction

macrophages produce high levels of what substances that promote inflammation?

IL-1 (interleukin-1) & tumor necrosis factor (TNF-α) — cytokines

adherence

microbes physically adhere to surface receptors on phagocyte

• ex. lectin receptor, mannose receptor

opsonization

• enhances phagocytosis

• microbes are coated in protein that bind to receptors on macrophage/neutrophil cell membrane

  • antibodies → Fc receptors

  • complement proteins (C3b) → complement receptors

3 mechanisms of microbial destruction (phagocytosis)

• lysosomal enzymes

• reactive nitrogen intermediates → nitric oxide (NO)

  • produced by iNOS (inducible nitric oxide synthase)

• reactive oxygen species (respiratory burst)

respiratory burst

• production of reactive oxygen species to kill microbes

• NADPH oxidase complex converts O₂ → O₂^- superoxide anions → H₂O₂ hydrogen peroxide → HOCl hypochlorite (bleach)

neutrophil extracellular traps

• mixture of cellular contents (chromatin, histones, cathepsins, elastase, myeloperoxidase) released right before neutrophil dies

• traps nearby microbes → digested by enzymes