Micro: Immunology 1: innate, lecture 14

Innate immunity

• Physical barriers, chemical barriers, cellular defense

• immediate response, non-specific/no memory, always ready

Adaptive immunity

Active immunity: natural and vaccination

Passive immunity: maternal and artificial

Barriers to infection: skin

• protective shield covered w/ keratin made by keratinocytes

• sebum(oily substance) covers and protects the skin

• acidic pH inhibits bacterial growth

• competition between species limits colonization by pathogens

• constant shedding removes outer epithelial skin layers

Barriers to infection: mucus membranes

• selectively permeable for nutrients and waste products

• mucus coats epithelial surfaces and traps microbes

• lysozyme: cleaves cell wall peptidoglycan

Barriers to infection: lungs

• cilia lines the nasal cavity

• sneezing/coughing

• respiratory mucociliary escalator

Chemical barriers to infection

• acidic pH of the stomach is lethal to most bacteria

• Enzymes, such as lysozyme in tears degrade bacterial cell walls

• Defensins are antimicrobial peptides made by a variety of cells such as skin, lung, genitourinary tract, and gastrointestinal tract and kills by destroying microbial cytoplasmic membrane

Cells of the INNATE immune system

• originate from bone marrow stem cells

• leukocytes= white blood cells

• Macrophage, dendritic cells, mast cells, neutrophil, eosinophil, basophil

How are microbes detected?

• Host and immune cells can recognize an infection or foreign agents through their microbe associated molecular patterns

• Ex: Flagella, cell wall components, peptidoglycan, etc

Neutrophils

• first responder to infection

• make up majority of wbc in blood

• can engulf by phagocytosis- eat cell

• engulf pathogen in phagosome vacuole that kills microbes after merge with lysosome

1) phagocytic wbc engulf the microbes

2) microbes are internalized in phagosomes and broken down in phagolysosome

Neutrophil NETosis

• released to trap and neutralize pathogens

• web-like networks of primarily DNA and antimicrobial enzymes

• could be suicidal or vital NETosis

Macrophages

• widely distributed throughout the body

• phagocytes (engulf bacteria)

• “present” antigens

Antigens

a piece of any enemy your immune system can recognize

Dendritic cells

• phagocytic

• antigen-presenting, can use soluble (free-floating) antigens

• common in skin, lungs, gut and can travel to lymph nodes

Eosinophils

• not effective at phagocytosis

• release toxins that target parasites, too large to phagocytose

• also involved in allergic reactions

• can contribute to asthma

Basophils

• make up <1% of wbc

• trigger allergic reactions

• release histamine- drives vessel dilation and permeability

Mast cells

• similar to basophils in structure

• contain many granules rich in histamine(causes vasodilation) and heparin which play a role in inflammatory response

• reside in connective tissues and mucosa and do not circulate in the bloodstream

How are all theses cell communicating?

• signaling proteins or molecules allows the immune system to coordinate and calibrate to the appropriate threat

• released by tissue or immune system

Cytokines

• inform immune cells to ramp up or down response, ex: interleukins or interferons

chemokines

• chemical attractants, ex: neutrophils migrate towards specific chemokines released by inflamed tissue

What is inflammation?

• a natural part of the body’s reaction to injury and infection, and is essential to body’s healing process

• while it’s helpful in the short-term, inflammation is destructive to human cells, tissues, and organs

The inflammation response: infection, step 1

• microorganisms grow and produce cell damaging compounds

The inflammation response: macrophages at the site, step 2

• phagocytosis and release signals like cytokines to communicate with other cells

The inflammation response: Vascular dilation and permeability, step 3

• to allows more leukocytes to enter the infection site, signaling proteins like prostaglandins, bradykinin, and histamines make blood vessels widen and become permeable

• more permeability= more swelling, redness, heat at infection site

• These also stimulate pain receptors

• stop prostaglandin=stop pain

• Ex: NSAIDS: ibuprofen/aspirin

The inflammation process: neutrophil infiltration, step 4

• neutrophils are often first recruits

• neutrophils follow signals and enter the site through capillary walls

The inflammation process: step 5

After pathogen is destroys, anti-inflammatory signals are released to resolve inflammation

sepsis

• a life-threatening, body-wide overreaction of the immune system to an infection

• triggered when microbes or their body parts. Ex: LPSendotoxin set off inflammation throughout the body instead at one site

• Ex: UTI, pneumonia, appendicitis

Early signs of sepsis

• fever(or abnormally low temperature), fast breathing, fast heart rate, high( or sometimes low) WBC count

Severe signs of sepsis

• confusion, kidney damage, abnormal blood clotting, which are signs that organs are starting to fail

septic shock

• blood pressure drops dangerously low and stays low even with treatment

• about 30-40% of patients with septic shock die

• 1 in 3 patients who die in the hospital have sepsis

Fever(pyrexia)

• normal body temperature is 96.8 F-100.4F

• Fever is greater than 100.4F (greater than 106.7F causes brain damage)

• slows bacterial growth and stimulates inflammatory response

Pyrogens

• substances that cause fever

• Ex: bacterial toxins, immune signals(interferons, cytokines, etc

• hypothalamus within the brain regulates temp in response to pyrogens

• prostaglandins also regulate fever

• NSAIDS=fever reducer

Chronic inflammation

• a slow, long term inflammation lasting months or years

• persistent presence of a foreign body, such as pathogens lingering in an unresolved infection, which may cause permanent tissue damage

• Ex; TB(avoids host defense), protozoa

• in some cases, infection could be walled off by leukocytes-granuloma

• conditions such as inflammatory bowel disease CD/UC have perpetual stimulation of inflammation in the gut even in beneficial microbes

The complement system

• A collection of over 50 proteins in the blood that help prevent blood infections

• Produced in the liver

• Triggering the complement cascade produces several outcomes:

• destroys the membrane of the pathogen, forms pores

• attracts WBC

• Induces inflammation