Innate immunity refers to
antigen-nonspecific defense mechanisms that a host uses immediately or
within several hours after exposure to an antigen
. This is the immunity one is born with and is
the initial response by the body to eliminate microbes and prevent
Unlike adaptive immunity,
innate immunity does not recognize every possible antigen. Instead, it
is designed to recognize a few highly conserved structures present
in many different microorganisms. The structures recognized are
called pathogen-associated molecular patterns and include LPS
from the gram-negative cell wall, peptidoglycan, lipotechoic acids
from the gram-positive cell wall, the sugar mannose (common in
microbial glycolipids and glycoproteins but rare in those of humans),
bacterial DNA, N-formylmethionine found in bacterial proteins, double-stranded
RNA from viruses, and glucans from fungal cell walls. Most body
defense cells have pattern-recognition receptors for these
common pathogen-associated molecular patterns and so there is an immediate response against
the invading microorganism. Pathogen-associated molecular patterns can
also be recognized by a series of soluble pattern-recognition
receptors in the blood that function as opsonins and initiate the
complement pathways. In all, the innate immune system is thought to
recognize approximately 103 molecular patterns. All of this
will be discussed in greater detail in upcoming sections.
The innate immune
phagocytic cells (neutrophils,
monocytes, and macrophages);
cells that release
inflammatory mediators (basophils, mast cells, and eosinophils);
natural killer cells (NK
molecules such as
complement proteins, acute phase proteins, and cytokines.
Examples of innate
immunity include anatomical barriers, mechanical removal, bacterial
antagonism, pattern-recognition receptors, antigen-nonspecific defense
chemicals, the complement pathways, phagocytosis, inflammation, and
fever. In the next several sections we will look at each of these in
We will now take a closer
look at the body defense cells located in the blood.
Defense Cells in the Blood:The Leukocytes
are critical to body defense. There are normally
between 5,000-10,000 leukocytes per cubic millimeter (mm3)
of blood and these can be divided into five major types: neutrophils,
basophils, eosinophils, monocytes, and lymphocytes. The production
of colonies of the different types of leukocytes is called
and is induced by various cytokines
known as colony stimulating factors or
A complete blood
is a laboratory test which, among other things,
detemines the total number of both leukocytes and erythrocytes
per ml of blood. In general, an elevated WBC
) is seen in infection, inflammation, leukemia,
and parasitic infestations. A decreased WBC count (leukopenia
) is generally seen in bone marrow depression,
severe infection, viral infections, autoimmune diseases,
malignancies, and malnutrition. For example, infections may increase
the total leukocyte count two to three times the normal level by
dramatically increasing the number of neutrophils.
A differential white
blood cell count (leukocyte differential count)
determines the number of each type of
leukocyte calculated as a percentage of the total number of
leukocytes. This information can be useful diagnostically because
different diseases or disorders can cause an increase or a decrease
in the various types of WBCs. For example, when doing a differential
WBC count, neutrophils are usually divided into
segs (a mature neutrophile having a segmented nucleus) and
bands (an immature neutrophil with an incompletely segmented or
banded nucleus). During an active infection, people are
generally producing large numbers of new neutrophils and
therefore will have a higher percentage of the immature band
forms. (An increase in band forms is sometimes referred to as a
"shift to the left"
because on laboratory slips used for
differential WBC counts, the heading for bands is to the left of the
heading for mature neutrophils or segs.)
The five types of
leukocytes fall into one of two groups, the polymorphonuclear
leuckocytes and the mononuclear leukocytes.
Polymorphonuclear leukocytes (granulocytes)
have irregular shaped nuclei with several
lobes and their cytoplasm is filled with granules containing
enzymes and antimicrobial chemicals. They include the following:
Neutrophils are the
most abundant of the leukocytes, normally accounting for 54-75%
of the WBCs. An adult typically has 3,000-7,500 neutrophils/mm3
of blood but the number may increase two- to three-fold during
active infections. They are called neutrophils because their
granules stain poorly - they have a neutral color - with the
mixture of dyes used in staining leukocytes. The nucleus of a
neutrophil has multiple lobes.
are important phagocytes.
granules contain various agents for killing microbes.
These include lysozyme
, acid hydrolase
, and myeloperoxidase
. These agents kill microbes
intracellularly during phagocytosis but are also often
released extracellularly where they kill not only microbes but
also surrounding cells and tissue, as will be discussed later
release the enzyme kallikrein which catalyzes the
generation of bradykinins
. Bradykinins promote inflammation
by causing vasodilation
, increasing vascular permeability, and
increasing mucous production. They are also chemotactic for
leukocytes and stimulate pain.
release enzymes which catalyze the synthesis of
prostaglandins from arachidonic acid in cell membranes.
Certain prostaglandins promote inflammation by causing
vasodilation and increasing capillary permeability. They also
cause constriction of smooth muscles, enhance pain, and induce
e. They are short-lived,
having a life span of a few hours to a few days, and do not
multiply. However, the bone marrow makes about 80,000,000 new
neutrophils per minute.
normally comprise 1-4% of the WBCs (50-400/mm3 of
blood). They are called eosinophils because their granules stain
red with the acidic dye eosin, one of the mixture of dyes used
when staining leukocytes.
The nucleus of an
eosinophil typically appears lobed.
granules contain destructive enzymes for killing infectious
organisms. These enzymes include acid phosphatase,
, and proteinases
b. They are
capable of phagocytosis but primarily they release
their contents into the surrounding environment to kill
c. The substances
they release defend primarily against fungi, protozoa, and
parasitic worms, pathogens that are too big to be consumed by
d. They secrete
, chemicals that promotes inflammation
by causing vasodilation
and increasing capillary permeability.
They also secrete various cytokines.
e. Their life
span is 8-12 days.
make up 0-1% of the WBCs (25-100/mm3 of blood). They
are called basophils because their granules stain a dark
purplish blue with the basic dye methylene blue, one of the
mixture of dyes that is used when staining leukocytes.
Basophils have a lobed
, and prostaglandins
, chemicals that promotes inflammation
by causing vasodilation
, increasing capillary permeability, and
increasing mucous production. Basophils also heparin
b. Their life
span is probably a few hours to a few days.
have compact nuclei and have no visible
cytoplasmic granules. The following are agranulocytes:
make up 2-8% of the WBCs (100-500/mm3 of blood).
a. Monocytes are
differentiate into macrophages when they leave the blood and
enter the tissue. Macrophages and dendritic cells are very
important in phagocytosis and serve as antigen-presenting cells
in the adaptive immune responses (see below). They produce a
variety of cytokines
that play numerous roles in body defense.
c. They are long-lived
(life span of months) and can multiply.
represent 25-40% of the WBCs (1,500-4,500/mm3 of blood).
mediate the adaptive immune responses.
b. Only a small
proportion of the body's lymphocytes are found in the blood. The
majority are found in lymphoid tissue. In fact the collective
mass of all the lymphocytes in the human body is about the same
as the mass of the brain!
circulate back and forth between the blood and the lymphoid
system of the body.
d. They have a life
span of days to years.
e. There are 3
major populations of lymphocytes:
(B-cells) mediate humoral immunity (antibody
production) and have B-cell receptors (sIg) on their surface
for antigen recognition. Generally 10-20% of the lymphocyte
are B-lymphocytes. They differentiate into antibody-secreting
(T-cells) mediate cellular immunity (the production
of cytotoxic T-lymphocytes and cytokines) and regulate the
adaptive immune responses. Generally 60-80% of the
lymphocytes are T-lymphocytes. Based on biochemical markers on
their surface, there are two major classes of T-lymphocytes:
(CD4+ T-lymphocytes) have CD4 molecules
and T-cell receptors (TCRs) on
their surface for antigen recognition. They function to
regulate the adaptive immune responses through cytokine
(CD8+ T-lymphocytes) have CD8 molecules
and T-cell receptors (TCRs) on their surface for
antigen recognition. They differentiate into T8-suppressor
cells and cytotoxic T-lymphocytes (CTLs).
3. NK cells
(natural killer cells) are lymphocytes that lack B-cell
receptors and T-cell receptors. They kill cells bound by
antibody or lacking MHC-I molecules on their surface.