Micro - Ch 14 - Innate Immunity

Ilya Metchnikoff

discovered phagocytes - proposed that they destroy invading microbes

first line of defense

skin and mucous membranes

skin

difficult for microbes to penetrate

• dermis - tightly woven fibrous connective tissue

• epidermis - many layers of epithelial cells

  • outermost are dead, filled with keratin - repels water, maintains dry environment, continually slough off along with any attached microbes)  

mucous membranes 

lines digestive, respiratory, and genitourinary tracts 

constantly bathed in mucous secretions 

peristalsis of intestines & mucociliary escalator remove microbes 

antimicrobial substances

salt accumulates from perspiration

lysozyme degrades peptidoglycan 

peroxidase enzymes break down hydrogen peroxide 

lactoferrin binds iron 

defensins form pores in microbial membranes 

normal microbiota (flora)

collection of microorganisms that naturally live on and inside our bodies

surface receptors

serve as eyes and ears of cell

• usually span membrane, connect outside to inside 

• binding to specific ligand induces response 

adhesion molecules

allows cells to adhere to other cells

cytokines

voices of cells

• produced by cell, diffuse to others, bind to appropriate cytokine receptors to induce changes such as growth, differentiation, movement, and cell death 

• act at low concentration, effects local, regoinal, systemic 

chemokines

chemotaxis of immune cells

colony-stimulating factors (CSFs)

multiplication and differentiation of leukocytes

interferons (IFNs)

control of viral infections, regulation of inflammatory response

interleukins (ILs)

produced by leukocytes, important in innate and adaptive immunity

tumor necrosis factor (TNF)

inflammation, apoptosis 

pattern recognition receptors (PRRs)

detect pathogen-associated molecular patterns (PAMPs), see signs of microbial invasion

detect DAMPs (danger associated)

detect MAMPs (microbe associated) 

toll-like receptors (TLRs)

anchored in membranes of sentinel cells 

• cells see PAMPs in extracellular environment 

sentinel cells

immune cells that act as the body’s early warning system

NOD (nucleotide-binding oligomerization domain)-like receptors (NRLs)

found in cytoplasm

• detect bacterial components indicating that the cell has been breached 

• unleash series of events to protect host cell 

• some NRLs join cytoplasmic proteins to form an inflammasome (activates inflammatory response)

RIG (retinoic acid-inducible gene)-like receptors (RLRs)

found in cytoplasm

• detect viral RNA indicating infection - produce interferons 

• interferons cause neighboring cells to express inactive antiviral proteins 

alternative pathway

triggered when C3b binds to foreign cell surfaces

lectin pathway

pattern recognition molecules bind to mannose of microbial cells, interact with complement system components 

classical pathway

activated by antibodies bound to antigen, which interact complement system

activation of complement system produces three major outcomes

opsonization, inflammatory response, lysis of foreign cells

opsonization

C3b binds to bacterial cells and foreign particles, allows phagocytes to engulf more easily

inflammatory response

C5a attracts phagocytes to area, C3a and C5a increase permeability of blood vessels, induce mast cells to release cytokines

lysis of foreign cells

membrane attack complexes (MACs) formed by proteins C5b, C6, C7, C8 and C9 molecules assembling in cell membranes of gram negatives

chemotaxis

phagocytes recruited by chemoattractants (products of microorganisms, phospholipids from injured host cells) 

recognition and attachment

direct (receptors bind to mannose) and indirect (binding to opsonins)

engulfment

pseudopods surround, form phagosome

phagosome maturation and phagolysosome formation 

endosomes fuse, lower pH, lysosomes bring enzymes 

destruction and digestion

toxic ROS and nitric oxide produced, pH decreases, enzymes degrade, defensins damage membrane of invader, lactoferrin ties up iron 

exocytosis

vesicle fuses with cytoplasm, expels remains

attributes of Neutrophils

• act as rapid response team, move into area and eliminate invaders

• play a critical role in early stages of inflammation 

  • first to be recruited from bloodstream 

• kill microbes via phagocytosis 

acute inflammation 

short term, macrophages clean up damage by ingesting dead cells and debris 

chronic inflammation

if acute fails, macrophages, giant cells accumulate, and granulomas form

apoptosis

programmed cell death, does not trigger inflammatory response

pyroptosis

if pattern recognition receptors are triggered, cell may undergo cell death with inflammatory response