Innate Immunity – Jan. 11
- Innate immunity is the first line of defense against a pathogen. It is constantly ready to destroy a
pathogen. It is effective at stopping the majority of pathogens at an early stage.
- Properties of innate immunity: It is inherited from your parents – We are born with innate defenses.
It is well conserved in evolution, in that all humans have the same defenses. It is always initiated
when a pathogen contacts the body. It responds immediately to a pathogen and the pathogen is
usually eliminated before symptoms arise. Innate immunity has no memory – There is the same
immune response to identical pathogens with each exposure and it non-adaptive.
- Innate immune defenses: 1. Barriers – Block pathogen entry into tissues. 2. Innate cells and soluble
molecules – Rapidly eliminate pathogens that enter tissue. 3. If the innate immune system is
unsuccessful – Certain innate cells instruct the adaptive immune system to eliminate the pathogen.
- Barriers: Modes of pathogen entry into the body – 1. Skin (wound). 2. Respiratory tract (breathing).
3. GI tract (ingestion). 4. Reproductive tract. The last three are the main modes of entry for most
pathogens and they are mucosal layers. The main barrier that prevents pathogen entry is epithelial
cells. Endothelial cells are epithelial cells that line blood vessels. Mucus sits on top of epithelial cells
and forms an additional barrier. Epithelial cells have tight junctions. Skin has keratinizing stratified
squamous cells. The trachea has ciliated pseudostratified squamous cells. The pathogen must be able
to get through the epithelial cells, so these cells are an effective barrier.
- Additional barriers used to prevent pathogen entry: Mechanical (flushing out) – Sneeze, cough, blink,
peristalsis (vomit, diarrhea), tears, saliva, urine, feces, earwax, cilia, mucus. Chemical – Fatty acids
(skin), lysozyme enzymes (saliva, sweat, tears), pepsin (gut), low pH (stomach), antibacterial
peptides (intestine). Anti-microbial enzymes are secreted by activated epithelial cells. Epithelial cells
become activated when a pathogen comes in contact with them. These enzymes are natural
antibiotics. Their action is to destroy the cell wall of a pathogen. Microbiological – Normal flora
compete for nutrients and attachment to epithelium and can produce antibacterial substances.
- Commensals are the normal flora found in the body. Commensals can be found in the back of the
mouth, skin, intestine, and vagina.
- The colon is colonized by large numbers of commensal bacteria. Commensal bacteria sit on top of
epithelial cells (are located between epithelial cells and gut lumen) and they serve as an additional
barrier. Antibiotics kill bacteria. This includes both pathogenic bacteria and bacterial microflora.
Clostridium difficile gains a foothold once the commensal bacteria is killed and produces toxins that
cause mucosal injury to the epithelial cells. The pathogen can then enter into tissues. Neutrophils and
red blood cells leak into the gut between injured epithelial cells.
- Crohn’s disease: Inflammatory bowel disease, characterized by chronic inflammation of the GI tract.
One theory is that the body mounts an abnormal innate immune response against commensal
bacteria (normal flora) in the gut. Crohn’s is associated with a genetic mutation in the NOD2 gene.
Evidence of this is that a mutation of the NOD2 gene in