IL-2- T cell growth factor secreted by Ag-stim T helper cells; enhances

cytotoxicity of NK cells

Il-3- lymphokine secreted by activated T cells, major immunologic

mediator of myeloid diff; causes prolif of granulocytes and macs; diff of
megakaryocytic, erythrocytic, mast cell precursors

IL-5- B-cell diff factor produced by T helper cells and mast cells; causes
prolif of activated B cells, increased eosinophil; enhances IgM
secretion, class switching of IgA

IL-7- hematopoietic growth factor secreted by bone marrow stromal

cells; growth factor for T cell and B cell precursors; enhances cytotoxic
activity on lymphocytes and monocytes

IL-8- inflamm cytokine secreted by monocytes and macrophages;

chemotactic for both neutrophils and T cells; causes activation of
neutrophils to release lysosomal enzymes, leads to SOD production

IL-10- produced by activated T cells and mast cells; inhibits cytkine

synth and T cell prolif in presence of monocytes; inhibits IL-2 and IFN-g
production by T helper cells; enhances B cell diff  Ab response
increased

IL-13- produced by T helper cells; regulator of inflamm response b/c

inhibits activity and release of inflamm cytokines by macs

Vascoactive amines are histamine and serotonin (present in platelets

and enterochrommafin cells)

Complement system consists of 20 component proteins (and their

cleavage products), which are found in greatest concentration in
plasma; system functions in both innate and adaptive immunity for
defense against microbial agents; in process of complement activation,
a number of complement components are elaborated that cause
increased vascular permeability, chemotaxis, and opsonization.

The classical pathway is triggered by fixation of C1 to antibody

(IgM or IgG) that has combined with antigen, and proteolysis of C2
and C4, and subsequent formation of a C4b2b complex that
functions as a C3 convertase.

The alternative pathway can be triggered by microbial surface

molecules (e.g., endotoxin, or LPS), complex polysaccharides,
and cobra venom; involves a distinct set of plasma components
(properdin, and factors B and D); spontaneous cleavage of C3 that
occurs normally is enhanced and stabilized by a complex of C3b and a
breakdown product of Factor B called Bb; the C3bBb complex is a
C3 convertase.
In the lectin pathway, mannose-binding lectin, binds to
carbohydrate-containing proteins on bacteria and viruses and
directly activates C1

C3b generated by any of the pathways binds to the C3 convertase and

produces C5 convertase, which cleaves C5. C5b remains attached
to the complex and forms a substrate for the subsequent
binding of the C6-C9 components. Polymerized C9 forms a
channel in lipid membranes, called the membrane attack
complex, which allows fluid and ions to enter and causes cell
lysis.

C1INH interferes with the enzymatic activity of two of the

proteins in the C1 complex. Excessive complement activation is
also prevented by a number of proteins that act to inhibit MAC
formation (e.g., CD59, also called membrane inhibitor of
reactive lysis).

Deficiency of C3 results in increased susceptibility to infections that is

fatal unless treated. Deficiencies of the alternative pathway proteins
are also associated with defective resistance to infections.
Paradoxically, deficiencies of C2 and C4 are associated with
autoimmune diseases, notably systemic lupus erythematosus,
probably because of a failure to clear immune complexes that are
formed.

In late component and MAC deficiency the only infections these

patients appear to suffer from are by Neisseria organisms.

Bradykinin increases vascular permeability and causes contraction of

smooth muscle, dilation of blood vessels, and pain when injected into
the skin.

Activated Hageman factor (factor XIIa) initiates four systems involved

in the inflammatory response: (1) the kinin system, (2) the clotting
system, (3) the fibrinolytic system, which produces plasmin and
degrades the fibrin; and (4) the complement system, which produces
anaphylatoxins.

Arachidonic acid (AA) is a 20-carbon polyunsaturated fatty acid;

derived from dietary sources or by conversion from the essential
fatty acid linoleic acid.

Inflammatory Actions of Eicosanoids:

Vasoconstriction - TXA2, LTs C4, D4, E4; Vasodilation PGI2,

PGE1, PGE2, PGD2; Increased vascular permeability- LTs C4,
D4, E4; Chemotaxis-, leukocyte adhesion LT B4, HETE, lipoxins
5-lipoxygenase (5-LO) is the predominant enzyme in neutrophils. The
main product, 5-HETE, which is chemotactic for neutrophils, is
converted into a family of compounds collectively called leukotrienes.
LTB4 is a potent chemotactic agent and activator of neutrophil
functional responses, such as aggregation and adhesion of leukocytes
to venular endothelium, generation of oxygen free radicals, and
release of lysosomal enzymes.

The principal actions of lipoxins are to inhibit leukocyte

recruitment and the cellular components of inflammation.

Resolvins inhibit leukocyte recruitment and activation, in part

by inhibiting the production of cytokines. Thus, the anti-
inflammatory activity of aspirin is likely attributable to its
ability to inhibit cyclooxygenases (see below) and, perhaps, to
stimulate the production of resolvins.

In addition to platelet stimulation, PAF causes vasoconstriction

and bronchoconstriction, and at extremely low concentrations
it induces vasodilation and increased venular permeability with
a potency 100 to 10,000 times greater than that of histamine.

TNF and IL-1 are two of the major cytokines that mediate
inflammation; systemic responses include fever, loss of
appetite, slow-wave sleep, the release of neutrophils into the
circulation, the release of corticotropin and corticosteroids
and, particularly with regard to TNF, the hemodynamic effects
of septic shock—hypotension, decreased vascular resistance,
increased heart rate, and decreased blood pH

NO is synthesized from L-arginine by the enzyme nitric oxide synthase

(NOS)- eNOS and nNOS are constitutively expressed at low levels and
can be activated rapidly by an increase in cytoplasmic calcium ions.
Influx of calcium into cells leads to a rapid production of NO. iNOS, in
contrast, is induced when macrophages and other cells are
activated by cytokines (e.g., TNF, IFN-γ) or other agents.

Different granule enzymes serve different functions. Acid proteases

degrade bacteria and debris within the phagolysosomes, in which an
acid pH is readily reached. Neutral proteases are capable of degrading
various extracellular components. These enzymes can attack collagen,
basement membrane, fibrin, elastin, and cartilage, resulting in the
tissue destruction that accompanies inflammatory processes. Neutral
proteases can also cleave C3 and C5 directly, releasing
anaphylatoxins, and release a kinin-like peptide from kininogen.
Neutrophil elastase has been shown to degrade virulence factors of
bacteria and thus combat bacterial infections.[69] Monocytes and
macrophages also contain acid hydrolases, collagenase, elastase,
phospholipase, and plasminogen activator. These may be particularly
active in chronic inflammatory reactions; α1-antitrypsin, which is
the major inhibitor of neutrophil elastase

antioxidants were discussed in Chapter 1 ; they include: (1) the

copper-containing serum protein ceruloplasmin; (2) the iron-free
fraction of serum, transferrin; (3) the enzyme superoxide dismutase,
which is found or can be activated in a variety of cell types; (4) the
enzyme catalase, which detoxifies H2O2; and (5) glutathione
peroxidase, another powerful H2O2 detoxifier.

Nerve fibers containing substance P are prominent in the lung

and gastrointestinal tract. Substance P has many biologic
functions, including the transmission of pain signals, regulation of
blood pressure, stimulation of secretion by endocrine cells, and
increasing vascular permeability

Fanconi’s Syndrome- prox tubule dysfxn, can be hereditary or

secondary to renal damage from proteins (multiple myeloma,
amyloidosis), drugs (chemo, AGs), or toxins (heavy metals)

Benzodiazepines- maybe disturb intellectual functioning and

motor dexterity; have potential for dependence, withdrawl
seizures may occur

• clonazepam- general absence seizures; chronic txt of epilepsy

• flurazepam, quazepam- less potent, more slowly elim show no
rebound insomnia on discontinuation of txt
• alprazolam- panic disorders
• triazolam (short acting)- withdrawal of drug  rebound insomnia
• diazepam- grand mal, status epilepticus

• targets GABA(a) receptors, enhances GABA binding; increase

FREQUENCY of Cl- channel openings  hyperpolarization  inh
formation of APs
○ increase affinity of binding sites w/out changing total number
of sites
○ increases permeability of Cl-
• reduce anxiety (a2), sedative and hypnotic actions (a1),
anterograde amnesia (a1), anticonvulsant (a1), muscle relaxant (a2)
• diazepam for prolonged periods; cross tolerance w/ alcohol;
alprazolam may cause withdrawal rxns in 30%
• tx anxiety disorders, muscular disorders (MS and cerebral palsy),
amnesia (procedures), seizures, increases stage2 REM
• flurazepam- long acting, daytime sedation
• temazepam- for those who wake up a lot
• triazolam for those who can’t get to sleep; tolerance  withdrawal
 rebound insomniakl
• metabolized to active compounds  urine as glucuronides or
oxidized metabolites
• adverse effects- drowsiness and confusion (triazolam  daytime
anxiety, amnesia); use caution w/ liver dz, avoid in acute narrow
angle glaucoma

BENZO ANTAGONIST- FLUMAZENIL, IV ONLY, MAY 

WITHDRAWAL, SEIZURES
Barbiturates- largely replaces by benzos; can cause coma in
toxic doses; thiopental still used to induce anesthesia

MOA: interaction w/ GABAa receptors which enhances GABAnergic

transmission; DURATION of Cl- channel opening (as opposed to
benzos which deal with frequency of Cl- channel opening);
block excitatory glutamate receptors

Buspirone- long-term therapy for chronic anxiety w/ symptoms of

irritability and hostility; does not potentiate CNS depression of alcohol;
low potential for addiction; slower onset of action than benzos; no
muscle relaxation or anticonvulsant activity

Eczopiclone- effective for up to 6 months

Zaleplon, zolpidem- no anticonvulsant or muscle relaxing

properties; no withdrawal effects, exhibit minimal rebound
insomnia, little or no tolerance occurs

Barbiturates- induce tolerance, drug-metabolizing enzymes,

and physical dependence, and who severe withdrawal
symptoms; thiopental has rapid onset of action used to induce
anesthesia