46. Immune Mechanisms Flashcards
What types of immunity are there?
The immune system comprises
a system of cellular and non-cellular
biological mechanisms that defend
an organism against disease.
Immunity can be classified as non-specific (or innate) and specific (or acquired/adaptive).
Both types depend on the immune
system’s ability to distinguish
between self-and non-self-molecules.
Both types consist of humoral and
cell-mediated components.
The non-specific immune system
does not recognise the substance that is
being attacked,
but responds against pathogens
in a generic way, and does
not confer long-lasting immunity
against pathogens.
It is present from birth.
Specific immunity is antigen specific
and requires the recognition
of non self- antigens during
a process called antigen presentation.
It confers immunological memory
by the action of memory cells.
Non-specific/innate immunity
Non-specific/innate immunity
> Surface Barriers
> Inflammatory response:
> Activation of the alternative complement pathway:
> Phagocytosis:
> Surface barriers:
> Surface barriers:
• Mechanical:
skin, coughing and sneezing expels organisms; tears and urine flush away pathogens; mucus traps organisms
• Chemical:
antibacterial enzymes in tears,
saliva and breastmilk; hostile
acidic environment of stomach
• Biological:
lower GIT bacterial flora that
prevents overgrowth of
pathogenic bacteria.
> Inflammatory response
• One of the first responses
to infection or injury, mediated by
eicosanoids and cytokines.
• Eicosanoids produce prostaglandins, which cause fever and blood vessel dilation, and leukotrienes, which attract white blood cells (WBC) to the site of infection.
• Cytokines include interleukins
(communication between WBC),
chemokines (chemotaxis)
and interferons (antiviral activity).
• The symptoms of inflammation are
redness, swelling, heat and pain,
caused by increased blood flow
to the site of injury/infection.
> Activation of the alternative complement pathway:
• Complement is a biochemical enzyme system comprising more than 20 glycoproteins that, when activated, result in a rapid catalytic cascade and eventual target cell lysis.
• The complement cascade results in
opsonisation (coating) of target
cells and disruption of their cell membrane phospholipids, attraction of
immune cells, and increased vascular permeability.
• The classical complement pathway is a
specific immune response and
involves the binding of complement
to antibodies on the surface of pathogens.
• The alternative complement pathway is a non-specific immune response and involves the binding of complement to carbohydrates on the surface of microbes, but also to bacterial toxins and certain drugs.
> Phagocytosis:
> Phagocytosis:
• The leucocytes involved in
innate immunity include
neutrophils
(50–70%),
macrophages,
monocytes (2–6%),
eosinophils (1–6%),
basophils (1%),
mast cells and natural killer (NK) lymphocytes.
• Phagocytosis is the process of
ingestion of a microorganism,
another cell or cell fragments
by a phagocyte to form an intracellular phagosome.
This fuses with a lysosome,
which in turn releases
lysozymes, which digest the particle.
• Neutrophils are usually the first cells to
arrive at the site of infection,
and aside form phagocytosis,
they also release inflammatory mediators.
• Macrophages are abundant within
tissues and act as scavengers
of worn-out cells and
destroyers of foreign material by both
phagocytosis and
extracellular release of toxic chemicals.
They also release cytokines
(interleukins, interferon, tumour necrosis factor) and
complement protein, and
activate the adaptive immune system by
acting as antigen-presenting cells (APC).
• Monocytes are the circulatory
equivalent of macrophages.
• Basophils are the circulatory
equivalent of mast cells, both of which
release histamines in response to allergens.
• Eosinophils destroy parasites by
extracellular release of enzymatic granules,
and they may mediate hypersensitivity reactions.
• NK cells are lymphocytes that
destroy tumour cells and cells infected by viruses.
Specific Immunity
Specific immunity is so called
because it is antigen specific.
This allows for a stronger immune response
that confers immunological memory
for specific pathogens.
The major components include T and B lymphocytes, plasma cells, antibodies, the classic complement pathway, and immunological memory.
B lymphocytes are involved in
humoral immunity and
T lymphocytes in
cell-mediated immunity.
Both T and B lymphocytes have receptors that
recognise specific antigenic targets.
> T lymphocytes
• There are two major subtypes:
helper T and killer T cells.
Another subtype,
suppressor T cells,
is involved in modulation of the
immune response.
• T cells recognise pathogens
only after antigens
(small, processed fragments of pathogens)
bind to specific receptors
(known as MHC, or major histocompatibility complex)
on the surface of APC (e.g. macrophages).
• T cell receptors bind to this antigen–MHC
complex with the help of a co-receptor
(CD4 on helper T cells and CD8 on killer T cells).
• Killer T cells bind to antigen–MHC class 1,
and helper T cells to antigen–MHC class 2.
• After binding to the antigen complex,
T cells become activated and
begin to proliferate,
some of which branch into memory cells.
• Activated killer T cells release
cytotoxins, which results in apoptosis of
the host cell.
• Activated helper T cells
release cytokines that activate killer T cells,
B lymphocytes and macrophages.
> B lymphocytes and antibodies
• Antibodies on the surface of
B cells bind to specific antigens.
The Ag–Ab complex is taken up
by the B cell and lysed,
forming antigenic peptides
that are then presented,
bound to MHC 2
on the B cell surface.
• This complex is recognised
by helper T cells
that release lymphokines,
which in turn activate the B cell.
• Activated B cells proliferate
forming other B cells, plasma cells
and memory cells.
• Plasma cells are mostly found in lymph nodes,
spleen and bone marrow.
They produce and release
millions of copies of antibodies into
the circulation.
• Antibodies bind to antigen expressed
on pathogens,
marking them for destruction by
either phagocytosis
or the classic complement pathway.
• They can also bind directly to
bacterial toxins and modulate receptors
on host cells so that viruses and
bacteria cannot penetrate them.
• Antibodies
are composed of two heavy chains
and two light chains,
with a variable region at one end,
allowing them to recognise their
specific antigens.
• There are five main subtypes of antibody:
IgG (most abundant),
IgM (crucial in initial immune response),
IgE (response to parasites and allergies),
IgA (present in body fluids)
and
IgD (on cell surface of B lymphocytes).
What type of hypersensitivity reactions do you know?
Hypersensitivity reactions are
abnormal immune responses,
including allergies and autoimmunity,
that damage the body’s own tissues.
Reactions occur on second or repeated
exposure to the antigen involved.
They can be classified into four groups based on mechanism:
> Type 1 (immediate, or anaphylactic)
This is the classic
atopic/allergic response
and occurs
when IgE antibodies on the surface of
mast cells and basophils bind to drug antigen.
This causes the cells to degranulate, releasing histamines, serotonin, leukotrienes, platelet-activating factor and heparin into the circulation.
These mediators cause vasodilatation,
increased capillary permeability,
increased secretion of mucus
and smooth muscle spasm.
The reaction occurs less than
1 hour from exposure.
The most common peri-operative
culprits include neuromuscular blockers,
latex, antibiotics, dyes and NSAIDs.
> Type 2 (antibody-dependent cytotoxic hypersensitivity)
Circulating IgE and IgM bind to
antigen and activate macrophages,
NK cells and the classic complement pathway,
resulting in target cell lysis.
Examples include blood transfusion reactions, erythroblastosis fetalis, autoimmune haemolytic anaemia, hyper-acute graft rejection of a transplanted organ, heparin-induced thrombocytopenia type 2, Graves’ disease and myasthenia gravis.
Type 3 (immune-complex mediated)
Type 3 (immune-complex mediated)
Circulating antigen–antibody complexes
deposit in vessels and tissues
and activate the classic complement pathway.
They may also activate the release
of inflammatory mediators.
Type 3 reactions typically occur 4–10 days
after exposure to antigen and
can become chronic.
Many autoimmune diseases fall in this category:
serum sickness, systemic
lupus erythematosus, rheumatoid arthritis, and the glomerulonephritides (including post-streptococcal).
> Type 4 (delayed)
This is a cell-mediated immune response,
not involving antibodies or complement.
T cells previously sensitised to an
antigen become activated
on re-exposure and can damage
tissue either by direct toxic effects
or by releasing cytokines that
attract phagocytes to the area.
Reactions typically take 24–48 hours to occur.
Disorders of this type include contact
dermatitis
(including a reaction to the chemicals used in the production process of latex gloves),
chronic transplant rejection,
and the immune response to TB
(including the tuberculin test in
previously exposed individuals).
