Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 3

Immunity, Infection, & Inflammation 69

intracellular portions do not contain tyrosine kinase catalytic
domains, they activate cytoplasmic tyrosine kinases when
ligand binds to the receptors.
The effects of the principal cytokines are listed in Table 3–2.
Some of them have systemic as well as local paracrine effects.
For example, IL-1, IL-6, and tumor necrosis factor
α
cause
fever, and IL-1 increases slow-wave sleep and reduces appetite.
Another superfamily of cytokines is the
chemokine
family.
Chemokines are substances that attract neutrophils (see pre-
vious text) and other white blood cells to areas of inflamma-
tion or immune response. Over 40 have now been identified,
and it is clear that they also play a role in the regulation of cell
growth and angiogenesis. The chemokine receptors are G
protein-coupled receptors that cause, among other things,
extension of pseudopodia with migration of the cell toward
the source of the chemokine.

THE COMPLEMENT SYSTEM

The cell-killing effects of innate and acquired immunity are
mediated in part by a system of more than 30 plasma proteins
originally named the
complement system
because they “com-
plemented” the effects of antibodies. Three different pathways
or enzyme cascades activate the system: the
classic pathway,

triggered by immune complexes; the

mannose-binding lectin

pathway,

triggered when this lectin binds mannose groups in

bacteria; and the

alternative

or

properdin pathway,

triggered

by contact with various viruses, bacteria, fungi, and tumor

cells. The proteins that are produced have three functions:

They help kill invading organisms by opsonization, chemo-

taxis, and eventual lysis of the cells; they serve in part as a

bridge from innate to acquired immunity by activating B cells

and aiding immune memory; and they help dispose of waste

products after apoptosis. Cell lysis, one of the principal ways

the complement system kills cells, is brought about by insert-

ing proteins called

perforins

into their cell membranes. These

create holes, which permit free flow of ions and thus disrup-

tion of membrane polarity.

INNATE IMMUNITY

The cells that mediate innate immunity include neutrophils,

macrophages, and

natural killer (NK) cells,

large lympho-

cytes that are not T cells but are cytotoxic. All these cells re-

spond to lipid and carbohydrate sequences unique to bacterial

cell walls and to other substances characteristic of tumor and

transplant cells. Many cells that are not professional immuno-

cytes may nevertheless also contribute to innate immune

FIGURE 3–4
Members of one of the cytokine receptor superfamilies, showing shared structural elements.
Note that all the subunits
except the
α
subunit in subfamily 3 have four conserved cysteine residues (open boxes at top) and a Trp-Ser-X-Trp-Ser motif (pink). Many subunits
also contain a critical regulatory domain in their cytoplasmic portions (green). CNTF, ciliary neurotrophic factor; LIF, leukemia inhibitory factor;
OSM, oncostatin M; PRL, prolactin.
(Modified from D’Andrea AD: Cytokine receptors in congenital hematopoietic disease.
N Engl J Med
1994;330:839.)

Subfamily 1 Subfamily 2 Subfamily 3

α

α

β β

γ

ECF

Cytoplasm

Erythropoietin

G-CSF

IL-4

IL-7

Growth hormone

PRL

IL-3

GM-CSF

IL-5

IL-6

IL-11

LIF

OSM

CNTF

Sharedβ

subunit

Shared gp130

subunit

IL-2

IL-4

IL-7

IL-9

IL-15