Innate Immunity

Skin (1st line of defense)

top layer is made of dead cells filled with keratin

waterproof

shedding removes outer epithelial layers

flushing effect of sweat glands helps remove microbes

Mucous membranes of digestive, urinary, respiratory tracts and the eye

Moist and permeable

easier to cross without keratinized layer

mucous coat prevents entry and attachment of bacteria

Respiratory tract

nasal hair

cilia lining nasal cavity sweep debris upwards (mucocililary elevator) then swallowed to be killed by stomach acid

sneezing, coughing

Urinary tract

flushing of urine to remove bacteria from urinary tract

Skin and mucous membranes

sebaceous glands exert antimicrobial effect

secrete lysozyme that breaks down peptidoglycan in cell walls

lactic acid in sweat and fatty acid content are going to lower the skin pH to be acidic

Stomach

flush by peristalsis

hydrochloric acid

Intestines

digestive juices

bile

Defensins

small peptides that poke holes in cells

SurA pokes holes in E. coli

important for innate immunity

Phagocytosis overview

1. phagocytic cell attaches to bacterium

2. phagocyte pseudopods extend and engulfs organism

3. Ingests into phagosome, fusion with lysosome turn into phagolysosome

4. Enzymes will break down pathogen

5. waste material released

Recognizing alien cells and particles

Bacteria and viruses contain unique structure that immediately tag them as foreign

look for MAMPs (Microbial- associated molecular patterns; pili, LPS, flagella, cell wall)

our cells have PRRs (pattern recognition receptors) that look for MAMPs

TLRs (toll-like receptors)

also look for MAMPs

TLR4 looks for LPS (G-)

TLR2 looks for Techoic acid (G+)

PRRs (pattern recognition receptors)

can be inside cell to recognize structures hidden

signal pathways will produce cytokines (small peptides) after pathogen engulfed and tells other cells possible infection

Pathogens can produce a capsule around bacteria, so we must use Opsonization

antibodies’ arms bind to pathogen, stem will interact with immune cells

neutrophils and macrophages will bind to antibodies and engulf bacteria

Phagolysosome

permits anerobic and aerobic pathways

Anerobic (Lysozyme will break down peptidoglycan, Lactoferrin will trap iron and keep it away, Defensins will poke holes, Hydrolases will break down macromolecules)

Aerobic (oxidative/ respiratory burst, oxygen radicals (superoxide ion and hydrogen peroxide; they will damage DNA)

Ways pathogens can survive phagocytosis

• some live in phagolysosome

• escape from phagosome

• stays in phagosome but secretes proteins that prevent fusion with lysosome

• Can enter host cell and kill it by triggering apoptosis

complement system (C)

produce MACs (membrane attack complexes) that make large hole into membrane

are made in liver (inactive) and are activated by being cleaved

Complement system regulation (how body protects our immune system)

CD59 (protectin)

cell surface protein that inhibits MAC formation

Factor H (always active)

circulating protein that inhibits any C3b

During inflammation (2nd line of defense)

resident-macrophages engulf pathogens and secretes cytokines and chemoattractants to cause pain and swelling and alert neutrophils and granulocytes

Cytokines

more permeable membrane and causes dilation of blood capillary

secrete selectins and ICAMs/VCAMs on wall of capillary

Selectins

select for neutrophils and WBCs

attract WBCs/neutrophils and cause to roll on walls

ICAMs and VCAMs

stop neutrophil rolling and squeeze (extravasation) through gap of endothelial cells and go to site of infection

at the end of infection

inflammation ends

neutrophils trigger apoptosis

Interferon

interfere with pathogenic replication

two types

Type 1 Interferon

warn cells about intracellular pathogen

produced when cell infected, get out and bind to neighboring cells to warn

induce dsRNA-activated endoribonucleases to break down viral RNA and protein kinases to inactivate ribosomes

How is a fever generated

1. exogenous pyrogen (pathogen) is engulfed by immune cells (macrophages, lymphocytes), which activate immune cells

2. Endogenous pyrogen (cytokines; IL-1) travels through blood circulation

3. Anterior hypothalamus (prostaglandins reset hypothalamus to higher temperature)

4. increase “set point”

5. leads to fever (shivering, increased metabolism, vasoconstriction)

6. decreases body temperature (Crisis, vasodilation and sweating)

Why is a fever important

slows down replication

increases activity of neutrophils and macrophages