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• Microorganisms may occassionally breach the epithelial barrier, it is now the job of
the innate and adaptive IR to recognize and destroy these microbes
• When a pathogen is able to invade the tissues, an inflammatory response is almost
always elicited which may be initiated by resident immune cells already present in
the involved tissue:
• Macrophages, dendritic cells, histiocytes, Kupfer cells and mast cells
• Possess surface receptors known as PRRs (Pathogen-recognition
receptor), which recognize and bind to two subclasses of molecules:
PAMPs (pathogen associated-molecular patterns) and DAMPs (damage-
associated molecular patterns)
Inflammatory Response
• Characterized by (“PRISH”):
• Dolor (pain)
• Calor (heat)
• Rubor (redness)
• Tumor (swelling)
• Functio laesa
• Two phases:
• Vascular phase
• Involves the movement of plasma fluid, containing important
fibrin and immunoglobulins (antibodies), into inflamed tissue
• Cellular phase
• Extravasation of neutrophils, lymphocytes and monocytes
Innate Immune Response
• The innate IR relies on the recognition of molecules (Pathogen-associated
immunostimulants) that are common to many pathogens but are absent in the host
• Pathogen-associated immunostimulants stimulate inflammatory
responses and Phagocytosis
• Pathogen-associated immunostimulants
• Formylmethionine-containing peptides act as very potent chemoattractants for
neutrophils
• Peptidoglycan, Lipopolysaccharide (LPS) and Teichoic acids on bacteria
• Zymosan, glucan, and chitin of fungi
• Glycosylphosphatidylinositol in Plasmodium
• Short sequences in bacterial DNA
• Pathogen-associated immunostimulants are recognized by receptors
called pattern recognition receptors
• The receptors initiate the phagocytosis of the pathogen, and they
stimulate a program of gene expression in the host cell for stimulating
innate immune responses (Toll-like receptors - TLR)
The complement system is known to amplify and complement the activity of
the antibodies but some components of the complerment are alos pattern
recognition receptors and can be activated directly by pathogen-associated
immunostimulants. Complement can be activated thru three pathways, the
classical, MBL and the alternative pathways. When the classical or lectin
pathway is activated, the alternative pathway may also be activated through a
positive feedback loop, amplifying their effects. Smaller complement products
promote an inflammatory response by recruiting phagocytes and lymphocytes
to the site of infection.
Many of the mammalian cell-surface pattern recognition receptors
responsible for triggering host cell gene expression in response to pathogens
are members of the Toll-like receptor (TLR) family
o TLRs play important parts in innate immune recognition of pathogen-
associated immunostimulants
Its activation stimulates the expression of molecules that both
initiate an inflammatory response and help induce adaptive
immune responses
Abundantly found on the surface of macrophages and
neutrophils, as well as on the epithelial cells lining the lung and
gut
Act as a warning system to alert both the innate and adaptive
immune systems that an infection is developing
Some proinflammatory molecules stimulate endothelial cells to express
proteins that trigger blood clotting in local small vessels which occlude the
vessels and cut off blood flow >>> prevents the pathogen from entering the
bloodstream and spreading the infection to other parts of the body
• Viruses do not possess pathogen-associated immunostimulants.
• Infected cells initiate mechanism to eliminate the pathogen
• Two step process
• The cells degrade the dsRNA into small fragments (about 21–
25 nucleotide pairs in length) that bind to any ssRNA in the host
cell with the same sequence as either strand of the dsRNA
fragment, leading to the destruction of the ssRNA
• The dsRNA induces the host cell to produce interferon α (IFN-
α) and interferon β (IFN-β) with autocrine and paracrine
function
• The binding of the interferons to their cell-surface
receptors activates a latent ribonuclease, which
nonspecifically degrades ssRNA
• It also leads to the activation of a protein kinase that
phosphorylates and inactivates eIF-2 shutting down most
protein synthesis in the host cell
• Inhibits viral replication
• WBC persuade virally infected cells to destroy itself.
• IFNs also stimulate both innate and adaptive cellular immune
responses
• IFNs enhance expression of class I MHC, which present viral
antigens to cytotoxic T cells
• IFNs enhance the activity of NK cells inducing the infected cell
to kill itself by undergoing apoptosis
• NK cells selectively destroy cells that express low levels
of MHC I
END