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Chapter 15
The Innate Immune Response
A Glimpse of History
 Once it was determined that
microorganisms caused disease, scientists
began working on showing how the body
defended itself from them.
 In 1882, Elie Metchnikoff (Russian)
proposed that phagocytes (“cells that eat
cells”) were primarily responsible for the
body’s ability to destroy entering
microbes.
• The tissues and fluids of the human body
are ideal growth media for entering
microbes; however, the interior of the
body is generally sterile.
• To maintain this sterility, humans have
developed many lines of defense ranging
from barriers to sensors.
• Protection provided from these defenses is
termed innate immunity.
First line defenses
• Barriers that separate and shield the
interior of the body from the surrounding
environment.
• Anatomical barriers include skin and
mucous membranes; which separate the
interior from the exterior, but also secrete
antimicrobial substances.
• Sensor systems recognize when first line
barriers have been breached.
Two important sensor groups
• Toll-like receptors and NOD (nucleotidebinding oligomerization domain proteins)
are found on or within different cell types.
• They recognize compounds unique to
microbes and then alert host defenses.
Other defenses
 Phagocytes engulf and digest microbes and
cellular debris as well as alert for signs of invasion.
 Cytokines are proteins that function as chemical
messengers.
◦ When a cytokine binds to a receptor, it signals a
change in cell activities and give them certain powers
or prompt them to move to a specific location
 Inflammation is a coordinated response that
allows antibodies and other proteins to leak into
tissues.
15.2 First-Line Defenses
• Skin is the most visible barrier.
• Epidermis consists of tightly packed cells
with
– Keratin, a protective protein
• Mucous membranes (mucosa) are bathed
in mucus and other secretions that wash
microbes away.
• Mucus: Traps microbes
• The respiratory tract is lined with cilia to
propel microbes away from the lungs and
to the throat for swallowing.
Antimicrobial Substances
• Lysozyme – an enzyme that degrades peptidoglycan is
found in tears, saliva, and mucus.
– It is most effective against gram positive bacteria,
where the peptidoglycan of the wall is more exposed.
• Peroxidase enzymes are found in saliva and milk, as well
as within phagocytes.
• Lactoferrin is an iron-binding protein found in saliva,
mucus, and milk.
– Iron is an important component for growth.
Lactoferrin prevents the microbes from getting the
iron they need.
Normal flora
1. Compete with pathogens or alter the environment
2. Members often produce compounds that are toxic to
other microbes, thereby preventing their growth.
• In hair follicles, normal flora break down lipids of body
secretions releasing fatty acids that inhibit pathogen
growth.
3. Commensal microbiota: One organism (microbe)
benefits and the other (host) is unharmed
• May be opportunistic pathogens
15.3 The Cells of the Immune
System
• These cells can move from one part of the
body to another while traveling through
the circulatory system.
• Always found in normal blood, but
numbers will increase during an infection
15.4 Cell Communication
• In order to respond to a threat, cells must
be able to communicate in a cooperative
fashion.
• Cells receive signals from the external
environment and send the signals to the
appropriate places.
Surface receptors
• Membrane proteins to which certain signal
molecules bind.
• Each surface receptor is specific with
which molecule it will bind, and the
molecule that can bind is termed a ligand.
Cytokines
• Proteins that bind to certain receptors to
induce a change in the cell.
– They are short lived, but very powerful.
– They can act locally, regionally, or
systemically.
Cytokine Types
• Chemokines – chemotaxis (directed movement in
response to a chemical).
– Defense cells have receptors for these, and therefore,
they can migrate to appropriate regions.
• Colony-stimulating factors (CSFs) – stimulate growth
and differentiation of different types of leukocytes
• Interferons (IFs) – Antiviral uses.
– Induce fever, contribute to inflammation, and help
regulate adaptive immune response.
• Interleukins (ILs) – Various uses in both
innate and adaptive immunity.
– Induce adhesion, induce fever, activate
natural killer cells, promote antibody
responses, etc…
• Tumor necrosis factors (TNFs) –
Cytotoxicity for some tumors, kill target
cells, initiate inflammatory responses.
15.5 Sensor Systems
• Toll-like receptors are pattern recognition
receptors that allow cells to signify the
presence of microbes outside of the cell
• NOD proteins do the same, only for inside
the cytoplasm of the cell.
• When a microbe engages a TLR, a signal is
transmitted to the nucleus to begin the
expression of certain genes.
• This response can trigger chemokines, or
pro-inflammatory cytokines.
The Complement System
• Serum proteins activated in a cascade
• Activated by
– Antigen-antibody reaction
– Proteins C3, B, D, P and a pathogen
The Complement System
• C3b causes opsonization (enhanced
phagocytosis, usually by coating the particle
for ingestion with antibody or complement
components)
• C3a + C5a cause inflammation
• C5b + C6 + C7 + C8 + C9 cause cell lysis
Effects of Complement Activation
• Opsonization or immune adherence:
Enhanced phagocytosis
• Membrane attack complex: Cytolysis
• Attract phagocytes
Some Bacteria Evade Complement
• Capsules prevent C activation
• Surface lipid-carbohydrates prevent
membrane attack complex (MAC) formation
• Enzymatic digestion of C5a
15.6 Phagocytosis
• Phago: From Greek, meaning eat
• Cyte: From Greek, meaning cell
• Ingestion of microbes
or particles by a cell, performed by
phagocytes
15.7 Inflammation
• Acute-phase proteins activated
(complement, cytokine, and kinins)
• Vasodilation (histamine, kinins,
prostaglandins, and leukotrienes)
• Redness
• Swelling (edema)
• Pain
• Heat
15.9 Fever
• Abnormally high body temperature
• Hypothalamus normally set at 37°C
• Gram-negative endotoxin cause phagocytes to release
interleukin–1 (IL–1)
• Hypothalamus releases prostaglandins that reset the
hypothalamus to a high temperature
• Body increases rate of metabolism and shivering which
raise temperature
• Vasodilation and sweating: Body temperature falls (crisis)
• Advantages
– Increases
transferrins
– Increases IL–1
activity
– Produces Interferon
• Disadvantages
– Tachycardia
– Acidosis
– Dehydration
– 44–46°C fatal
Works Cited
• Nester, Anderson, Roberts and Nester.
Microbiology: A Human Perspective.
• Tortora, Funke, and Case. Microbiology: An
Introduction.