BIOS 250 unit 3 innate immunity

Nonspecific Innate immunity

first line of defense against infection by blocking entry of microbes and targeting them

a generalized and NONSPECIFIC set of defenses against a class or group of pathogens

ex: physical battlers, mechanical actions, and microbiome

Cellular barriers

deny entry to pathogens

ex: skin, mucous membranes, endothelial cells

Mechanical defenses

removes pathogens from sites of infection

ex: shedding skin cells (epidermis), mucociliary sweeping, peristalsis, flushing of urine and tears

Microbiome

Compete with pathogens for cellular binding sites and nutrients

ex: skin, upper respiratory tract, GI tract

Skin barrier

composed of 3 layers: epidermis, dermis, hypodermis

consists of certain

skin surface is very dry and salty so inhibits growth of microbes

Mucous membranes

lines the nose, mouth, lungs, urinary tracts

consists of epithelial cells bound by tight junctions that secrete mucus

Mucociliary escalator

system of removal in lungs

cilia propels mucus away from lungs

Peristalsis

muscular contractions in digestive tract, moves the mucus through intestines and rectum to excrete feces

Antimicrobial peptides (AMPs)

found on skin and produce in response to the presence of pathogens

may induce damage to cell, destroys DNA or RNA

inhibit only certain groups of microbes and more broadly effective against bacteria

ex: defensins, histatins, and bacteriocins

Defensins

produced by epithelial cells and combat microorganisms by damaging their plasma membranes

Complement system

group of plasma protein mediators that act as an innate nonspecific defense and are always present in the blood

has 3 pathways

Alternative pathway

initiated by activation of complement proteins C3

C3 produces C3a and C3b

When there is no invader, C3b degrades. If there is an invader, C3b attaches to surface and will recruit other complement proteins

C3a recruits leukocytes to site of infection

Classical pathway

activated by the production of antibodies, can be specific

Lectin pathway

similar to classical but is triggered by binding to sugar

lectins are produced by liver cells

Opsonization

coating of a pathogen that allows phagocytic cells to recognize, engulf, and destroy it more easily

Membrane attack complex (MAC)

creates pores into cell wall of gram-negative bacteria which allows water and ions to move freely in and out of cells, leading to cell lysis and death

only effective against gram-negative

Cytokines

soluble proteins that act as communication signals between cells

play a key role in inflammatory response, triggering production of histamine, prostaglandins, and bradykinin

has 3 classes

Interleukins

produced only by WBCs and stimulate leukocytes

Chemokines

recruit leukocytes to sites of infection

Interferons

important in defense against viruses

Interferon type 1

produced and released by cells infected with viruses

Interferon type 2

important activator of immune cels

Granulocytes

visible granules

ex: neutrophils (PMN), eosinophils, basophils, mast cells

Neutrophils

found in largest numbers in bloodstream

release toxic molecules as first responders, involved in elimination and destruction of extracellular bacteria

mechanisms include NETs and release histamine

Neutrophil extracellular traps (NETs)

extruded mesh of chromatin that is coupled with antimicrobial proteins so neutrophils can mount a highly concentrated and efficient attack against pathogens

Eosinophils

targets protozoa and helminths

involved in inflammation

Basophils

involved in inflammation and release histamine

Mast cells

function similarity to basophils, are found in tissues outside the bloodstream (close to surface)

Agranulocytes

lack visible granules

ex: Monocytes, Macrophages, Dendritic cells

Monocytes

circulate blood, largest immune cell, patrols

effective phagocytes, engulfing pathogen, and apoptotic cells to help fight infection

once they leave bloodstream, they differentiate into macrophages and dendritic cells

Macrophages

provide immune protection and normal function of neighboring tissue, police

Dendritic cells

found in skin and mucous membranes

communicate between adaptive immune system and innate immune system

Phagocytes

recognize pathogens and destroy through phagocytosis

Pathogen-associated molecular patterns (PAMPs)

phagocyte receptors that are located on pathogens

ex: peptidoglycan, flagellin, LPS, lipopeptides, nucleic acid

Pattern recognition receptors (PRRs)

allow phagocytic cells to detect PAMPs, surface receptors on leukocytes

Toll-like receptors (TLRs)

type of PRR found on phagocytes, bind to various PAMPs and communicate with nucleus of phagocyte to elicit a response

Phagocytosis

engulfs pathogen, killing and digesting it

Phagosome

needed to engulf pathogen, forms a pseudopod that wraps around the pathogen and pinches off into a membrane

Phagolysosome

phagosome fuses with lysosomes to enhance acidification

Acute inflammation

short lived and immediately follows and injury

1) Vasoconstriction to minimize blood loss after injury

2) mast cells release histamine

3) Vasodilation and vascular permeability occur

4) Dendritic and mast cells recruits neutrophils first, then immune components

5) Pus forms and macrophages clean up

Chronic inflammation

inflammatory response is unsuccessful, long lasting

forms granulomas

Granulomas

pockets of infected tissue walled off and surrounded by WBCs

Fever

system-wide sign of inflammation that raises body temperature

regulated by hypothalamus which maintains homeostasis, cytokines released during inflammation

Pyrogens

chemicals that alter the thermostat setting of hypothalamus, may be exogenous or endogenous

Interleukins indirectly interact with hypothalamus