Lecture 3 Innate Immunity Part I

Innate Immunity

-Generalized response
-Has no memory
-Fast-acting, always present
-Born with this system
-Evolutionarily older process

Adaptive immunity

-Specific response
-Has memory
-Slow-acting, must ramp up
-Acquire this system
-Key feature of vertebrates

External Defenses

1st line of defense
includes:
-Physical barriers
-Chemical barriers
-Biological barriers

Immune system mechanism

-Safeguard us from infections
-Surveil our body for intruders
-Maintain protective responses against harmful elements

Physical barriers

keep hazardous organisms and materials outside the body
includes: skin, mucosal membranes, hair, cilia, etc.

skin

physical barrier
Epidermis - outer layer of dead, tightly-packed keratinized cells
-shedding of dead skin cells removes attached microorganisms; Few pathogens can penetrate layers
Dermis - collagen protein fibers give strength and pliability to resist abrasions

mucosal membranes

physical barrier lining respiratory, digestive, urinary, conjunctival, and reproductive
-line all body cavities open to the outside envrioment
-Living epithelial cells tightly packed to prevent pathogen entry
-Continual shedding of cells carries attached microorganisms away

hair

physical barrier
Hair Follicles (Nasal hair, Eyelashes, Eyebrows, Body hair, etc.)
-Trap dirt, debris, and potentially harmful microorganisms
-Eyelashes - Eyelid movement sweeps airborne dirt/debris/microorganisms away from the eye

Cilia

physical barrier
-Beat in concerted waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways
-Sneezing or coughing ejects mucus and pathogens from the nose and throat

Chemical barriers

Antimicrobial Peptides
found on the skin, mucosal membranes, and in phagocytes
- increases their antimicrobial activity
Examples:
-Defensins
-Lactoferrin
-Dermcidin

Antimicrobial Peptides (AMPs)

small, positively charged amino acid sequences naturally found in the innate immune system (a.k.a. antimicrobial enzymes)

Sweat

chemical barrier secreted by sweat glands; contains antimicrobial peptides (Defensins)
-salt inhibits pathogen growth by drawing water from microbial cells (osmosis)

Sebum

chemical barrier secreted by sebaceous (oil) glands; lowers skin pH to inhibit bacterial growth
-helps keep skin pliable and less likely to break or tear

Mucus

chemical barrier that lines mucosal membrane surfaces to trap dirt and microbes
-every day, you swallow and digest about 1 liter of mucus

Lysozyme

chemical barrier that destroys bacterial cell walls
-A primary component of saliva and tears

Tears

chemical barrier that is a heterogenous mixture of water, lipids, mucus, electrolytes, and proteins
-contain antibacterial enzymes (Defensins, Lysozyme, and Lactoferrin) and high quantities of IgA

Urine

chemical barrier that flushes out the organs of the urinary tract
-Bladder epithelial cells secrete antimicrobial compounds into the urine

Saliva

chemical barrier secreted by the salivary glands; regulates oral pH to inhibit bacterial growth
-contains antibacterial enzymes (Defensins, Lysozyme, and Lactoferrin) and high quantities of IgA

Cerumen

chemical barrier that is an oily emulsion that coats and protects the ear
-Traps dust and repels water; maintains a low pH to inhibit bacterial growth

Stomach Acid

chemical barrier with a low pH (2) kills most harmful microbes

Biological barriers

living organisms that help protect the body from pathogens (Microbiome)

-trillions of harmless bacteria, protists, and fungi live on the human skin and in the urinary, reproductive, and gastrointestinal tracts.

-these bacteria use up food and surface space that help prevent pathogenic bacteria from colonizing the body

-Some harmless bacteria also secrete substances that changes conditions of their environment, making them less hospitable to potentially harmful bacteria

-reduce the chances that pathogenic microorganisms can reach sufficient number to cause illness

Internal Defenses

2nd line of defense
includes interferons, immune cells, complement system, and inflammation

Interferons

a group of proteins manufactured by cells in response to viral infections

Abbreviated IFN or IF

Produced by virus-infected cells to signal neighboring cells.

-interfere with viral replication

-Enhance phagocyte activity

-Stimulate antibody production

-Enhances NK cell killing power

-Slow cell division and tumor growth

Innate Immune cells

derived from myeloid precursors
"Never Let Monkeys Eat Bananas!"
-Neutrophils, Lymphocytes, Monocytes, Eosinophil, and Basophil

Antigen-Presening cells

present antigen (i.e., pieces of phagocytized bacteria) to T-cells in the adaptive immune system
-Macrophages, Dendritic cells, and Select B-cells

Polymorphonuclear Leukocytes

Also known as granulocytes
-Short-lived phagocytic cells
-Contain lysosomes to break down infectious microorganisms
-Produce peroxide, superoxide radicals, and nitric oxide (toxic to cells)
-Defects in PMN cell function result in chronic/recurrent infection

Macrophage

phagocyte that engulf/break down trapped materials and take up antigens, process them, and present them to T-cells

-following tissue migration, undergo additional differentiation based on location

-Members of the reticuloendothelial system

Dendritic cells

specialized white blood cells that patrol the body searching for antigens that produce infections
-phagocytes
-Most efficient APCs
-varying cell lines (myeloid and lymphoid varieties)

Natural Killer (NK) Cells

play an early role in terminating viral-infected cells or tumor cells

-in between innate and adaptive

Two receptors control whether NK cells will eliminate host cells:

-Inhibitory Receptor = Major Histocompatibility complex (MHC) Class I

-Activating Receptor = Killer-Cell Inhibitory Receptors (KIRs)

Viral-infected cells and tumor cells DO NOT express sufficient MHC class I molecules to prevent termination

-NK cell releases perforin and granzymes to cause cell lysis

Innate Lymphoid cells

come from lymphoid tissue
Various subsets have different roles and different locations.

Act in early stages of immune response as it transitions to adaptive response.