4. Immunology (and Drug Reactions) Flashcards
Basic components of the immune system.
Innate or Non-Specific Immunity
Acquired or Specific Immunity
Innate or Non-Specific Immunity
The body has a number of non-specific defences against infection.
These include the skin;
the antimicrobial secretions of sweat,
sebaceous and lacrimal glands;
and the mucus of the gastrointestinal tract
and the upper airway to which organisms may adhere.
The acidic environment of the stomach is hostile,
the lower gut is populated with commensals which
prevent the overgrowth of less benign species
Non-specific immune defences do not recognize the substance
that is being attacked and are activated immediately
in response to potential threats,
These defences include the activation of the
alternative complement pathway (see following),
phagocytosis by neutrophils, macrophages and mast
cells, and the inflammatory response itself.
Inflammatory response:
this allows cells and proteins to reach extravascular sites by
increasing the blood supply by vasodilatation
by increasing vascular permeability,
by encouraging the movement of various inflammatory cells
to the site of injury
by activating the immune system.
Leucocytes:
- neutrophils (60–70% of the total),
which are responsible for phagocytosis
inflammatory mediator release; - basophils (1%), which are the circulatory equivalent
of tissue mast cells; - monocytes (2–6%),
which function in the blood like macrophages; - eosinophils (1–4%),
which destroy helminths and other parasites,
and which may mediate hypersensitivity reactions; - Lymphocytes (20–30%).
Most lymphocytes mediate specific immune defences,
but NK (natural killer) lymphocytes bind non-specifically
to tumour cells and to virus-infected cells
Macrophages
These are ubiquitous cells that are derived from monocytes.
They destroy foreign particles by phagocytosis,
mediate extracellular destruction via the secretion of
toxic chemicals and also secrete cytokines.
These are a complex set of soluble protein messengers
that regulate immune responses and
include the interleukins, tumour necrosis factor,
colony-stimulating factors and interferons.
Acquired or Specific Immunity
Lymphocytes
Specific immunity involves recognition of cells or substances to be attacked,
lymphocytes are the mainstay of the specific immune system.
B lymphocytes differentiate into plasma cells
which synthesize and secrete antibody.
T lymphocytes comprise helper cells (T-helper, Th)
killer cells (cytotoxic, Tc).
NK cells are non-specific.
Th cells produce a large number of cytokines in a process
that links the innate and specific components of the immune system.
Antibodies
These immunoglobulins are proteins which bind specifically with antigens,
which contain two identical
light and two identical heavy chains, and which are
characterized as IgA, IgD, IgE, IgG and IgM.
IgG is the most abundant and is the
only immunoglobulin which crosses the placenta.
Drug Reactions
Not all of the described hypersensitivity reactions
are necessarily involved in drug reactions,
but a summary is included
for completeness.
Hapten formation
Most drugs are of low molecular weight and are not inherently immunogenic;
they can, however, act as haptens by interacting with proteins to form
stable antigenic conjugates
Hypersensitivity reactions:
classification of hypersensitivity into four types was originally described
by Gell and Coombs
these are abnormal reactions involving different immune mechanisms,
often with the formation of antibodies.
They occur on second or subsequent exposure to the antigen concerned.
Four types have been described
Type I (immediate)
Type II (cytotoxic):
Type III (immune complex):
Type IV (delayed):
Type I (immediate)
the classic anaphylactic, immediate hypersensitivity reaction,
which is mediated by IgE.
IgE is synthesized by B cells on first exposure to the antigen and binds to mast cells.
On repeated introduction,
the antigenic drug–protein complex degranulates mast cells
with the release of a number of preformed vasoactive substances.
These include histamine, heparin, serotonin,
leukotrienes and platelet-activating factor.
(Mast cells are numerous in skin, the
bronchial mucosa, in the gut and in capillaries.)
The term ‘immediate’ may mask
the fact that Type I reactions can be biphasic, with a secondary response occurring
up to 72 hours after the initial event but without re-exposure to the antigen.
Type II (cytotoxic):
Circulating IgE and IgM antibodies react
in the presence of complement to mediate reactions which cause cell lysis.
Such reactions can lead to
haemolysis (caused, for example, by sulphonamides),
thrombocytopenia (heparin, thiazide diuretics)
agranulocytosis (carbimazole, NSAIDs, chloramphenicol).
Type III (immune complex):
antibody and antigen produces a circulating immune complex (precipitin),
which deposits in small vessels,
in the glomeruli and
in the connective tissue of joints.
These precipitins also activate complement via the classical pathway.
Type III reactions underlie
many autoimmune diseases,
including rheumatoid arthritis and systemic lupus erythematosus (SLE).
Type IV (delayed)
Delayed hypersensitivity reaction,
which is cell-mediated without
complement activation
without the formation of antibodies.
The reaction results from the combination of antigen with T (killer) lymphocytes
and macrophages attacking the foreign material.
This mechanism underlies the development of contact dermatitis.
Granuloma formation in diseases such as tuberculosis
sarcoidosis is a result of a large antigen burden or
the failure of macrophages to destroy the antigen.
This ‘granulomatous hypersensitivity’ is also a Type IV response.
Complement
: complement is an enzyme system consisting
of 20 or more serum glycoproteins which,
in combination with antibody,
are activated in a cascade that results in cell body lysis.
In summary,
the complement system coats (opsonizes)
bacteria and immune complexes,
activates phagocytes and destroys target cells.
