Innate Immunity
• The inflammatory response is depicted in this
graphic:
• Edema results from
increased permeability
of blood vessels.
• Pain is a prime symptom
which results from
sensitization of nerve
endings by the
inflammatory chemicals.
Adaptive Immunity
• Substances recognized as foreign that provoke
an immune response are called antigens (Ag).
• Adaptive immunity describes the ability of the
body to adapt defenses against the antigens of
specific bacteria,
viruses, foreign tissues…
even toxins (think of the
snake handler who
becomes immune to the
venom of snake bites).
Adaptive Immunity
• Two properties distinguish between adaptive
immunity and innate immunity:
1. Specificity for foreign molecules which act as Ag
• this involves distinguishing self-molecules (normal, not
antigenic) from nonself molecules
2. Memory forpreviously
encountered Ag
Adaptive Immunity
• Not all foreign substances are antigenic: We
don’t make antibodies to glass, for example.
Molecules, or parts of molecules tend to be
antigenic if they are:
• Foreign – not ourselves
• Organic
• Structurally complex (proteins are usually complex
and form many of the most potent antigens)
• Large (high molecular weight)
Adaptive Immunity
• Antigens can have multiple antigenic
determinants called epitopes.
• Each epitope is capable of producing
an immune response.
• Entire microbes may act as an
antigen, but typically just
certain small parts (epitopes) of
a large antigen complex triggers
a response.
Antigens can have multiple
antigenic determinants called
epitopes. Each epitope is capable
of producing an immune response.
Adaptive Immunity
• The adaptive immune response cannot get
started without the aid of the nonspecific
phagocytosis that occurs in the innate immune
response.
• The phagocytic cells that initiate the process are
called antigen presenting cells.
Adaptive Immunity
• Antigen-presenting cells (APCs) are mostly
dendritic cells and macrophages, and they
link the innate immune system
and the adaptive immune system.
– Dendritic cells are usually found
in tissues in contact with the
external environment, and they
are the most potent of the
antigen-presenting cell types.
Dendritic cells grow branched
projections called dendrites that
give the cell its name. However,
these do not have any special
relation with neurons which
possess similar appendages
Adaptive Immunity
• As an antigen-presenting cell engulfs and
destroys a foreign invader, it isolates
the antigens those cells
“display”.
• The APC then presents the foreign
Ag to a specific T lymphocyte
called a helper T cell
(also known as a CD4 cell) .
Processed Ag
is presented
Adaptive Immunity
• Once stimulated by antigen
presentation, helper T cells
become activated.
• Activated helper T cells are
capable of activating other
lymphocytes to become T
cytotoxic cells (CD8 cells) which
directly kill foreign invaders and B
cells (which make antibodies that
kill or helps kill foreign invaders).
Adaptive Immunity
• Activated B and T cells form the two arms of the
adaptive immune response: Antibody-mediated
immunity and Cell-mediated
immunity.
• Helper T cells aid
in both types, and
both types work
together to form
specific bodily
defenses.
The Innate and Adaptive Immune systems are depicted
Adaptive Immunity
• Cell-mediated immunity involves the production of
cytotoxic T cells that directly attack invading pathogens
(foreign invaders with Ag harmful to us – particularly
intracellular pathogens and some cancer cells).
• Suppressor and memory T cells are also produced.
• Antibody-mediated immunity involves the production of B
cells that transform into antibody making plasma cells.
• Antibodies (Ab) circulate in extracellular fluids.
• B memory cells are also produced.
Adaptive Immunity
• B-cells can be activated by
direct recognition of antigen
through B-cell receptors or
through T-helper cell
activation.
• Activated B-cells undergo
clonal selection to become
antibody producing plasma
cells.
Adaptive Immunity
MHC Molecules
• Our immune system has the remarkable ability,
and responsibility, of responding appropriately
to a wide variety of potential pathogens in our
environment.
• The proteins that are used as cell-markers to “flag”
self from non-self are called MHC molecules, and are
coded for by a group of genes called the major
histocompatibility complex (MHC).
• MHC genes are diverse, and vary greatly from individual to
individual.
MHC Molecules
• There are two general classes of MHC molecules,
and at least one or the other, or both, are found on
the surface of all nucleated cells in the body.
• Class I molecules (MHC-I) are built into almost all body
cells and are used to present non-self proteins (from
bacteria or viruses, for example) to cytotoxic T cells.
• Class II molecules (MHC-II) are only found only on APCs.

Both classes are important for antigen processing and presentation.
MHC Molecules
• When APCs come across foreign antigens, they are broken down
and loaded onto MHC-II molecules of APCs.
• The Class II MHC molecules on the APCs present the fragments to
helper T cells, which stimulate an immune reaction from other
cells.
• Clones of activated T cells (and the antibodies from plasma
cells) are now “competent” to recognize similar antigenic
fragments displayed by infected cells throughout the body
and respond harshly.
MHC Molecules
• Infected body cells present antigens using
MHC-1 molecules
MHC Molecules
• Cytotoxic T cell
destruction of an
infected cell by
release of perforins
that cause cytolysis
• Microbes are
destroyed by
granulysin.
Clonal Selection
• Clonal selection is the process by which a lymphocyte
proliferates and differentiates in response to a specific antigen.
• A clone is a population of identical cells, all recognizing the
same antigen as the original cell.
• Lymphocytes undergo clonal selection to produce:
• Effector cells (the active helper T cells, active cytotoxic T cells,
and plasma cells) that die after the immune response.
• Memory cells that do not participate in the initial immune
response but are able to respond to a subsequent exposure proliferating and differentiating into more effector and
memory cells.
Cytokines
• Cytokines are chemical signals from one cell that
influences another cell.
• They are small protein hormones that control cell
growth and differentiation:
•
•
•
•
Interferon
Interleukins
Erythropoietin
Tumor necrosis factor
Antibodies
• Antibodies (also called immunoglobulins or Igs) are produced by
plasma cells through antibody-mediated immunity.
• Antibodies are composed of 4 peptide chains:
• Two heavy chains and two light chains
• Disulfide bonds link the chains together in a Y-shaped
arrangement.
• The variable region (antigen-binding region) gives an
antibody its specificity.
• The stem is similar for each class of antibody.
Antibodies
• Single-Unit antibody structure
Antibodies
• Some of the ways antibodies are effective
include:
• Neutralizing a bacterial or viral antibody, or a toxin by
covering the binding sites and causing agglutination
and precipitation (making what was soluble,
insoluble)
• Activating the classical
complement pathway
• Enhancing phagocytosis a process called
opsonization
Antibodies
• The complement system is a series of blood
proteins that often work in conjunction with
antibodies – it can be activated by multiple
pathways in a step-wise or cascading fashion. It
encourages vasodilation and inflammation,
antigen opsonization,
and antigen
destruction.
• The main proteins
are C1-C9.
Antibodies
• A membrane attack complex (MAC) forms as a
result of activation of
the complement
cascade.
– The MAC
results in
lysis of the cell.
Antibodies
• There are 5 classes of antibodies:
• IgG – a monomer with two antigen-binding sites
• Comprises 80% of total antibody
• Only class able to cross the placenta
• Provides long-term immunity
• IgM – a pentamer with ten antigen-binding sites
• It is a great activator of complement, but has a short-lived
response.
• It is the first antibody to appear in an immune response
Antibodies
• Classes of Antibodies
• IgA – a dimer with four antigen-binding sites
• prevalent in body secretions like sweat, tears, saliva,
breast milk and gastrointestinal fluids
• IgE – a monomer involved in allergic reactions
• comprises less than 0.1% of total antibody in the blood
• IgD – a monomer with a wide array of functions,
some of which have been a puzzle since its discovery
in 1964
Antibodies
Classes of Antibodies
Antibodies
• Thousands of memory cells exist after initial
encounter with an antigen - this is called
Immunological Memory.
• With the next appearance of the same antigen,
memory cells can proliferate and differentiate within
hours.
• This graphic shows that
serum antibody titers
are much higher and
much faster on the
second response
Gaining Immunocompetence
• Within the framework of innate and adaptive
immunity we have discussed, there are a number of
designations for the ways we can become
immunocompetent:
• “Natural Immunity” is not gained through the tools of
modern medicine, whereas ”Artificial Immunity” is.
• Active Immunity refers to the body’s response to make
antibody after exposure to a pathogen (antigen).
• In Passive Immunity, the body simply receives antibodies
that have been preformed.
• Active immunity is long-term; passive is short-term.
Gaining Immunocompetence
• Examples
• Natural active – contracting hepatitis A and
production of anti-hepatitis A antibodies
• Natural passive - a baby receives antibodies from its
mother through the placenta and breast milk.
• Artificial active - a person receives a vaccine of an
attenuated (changed/weakened) pathogen that
stimulates the body to form an antibody.
• Artificial passive – an injection of prepared antibody
Immunological Surveillance
• A current theory purports that the formation of
cancer cells is a common occurrence in all of us,
and that the immune system continually
recognizes and removes them.
• There are a number of well-recognized tumor
antigens which are displayed on certain cancerous
cells.
• These cells are targeted for destruction by cytotoxic T cells,
macrophages and natural killer cells.
• Most effective in eliminating tumor cells due to
cancer-causing viruses
The Immune System and Aging
• Atrophy of the thymus gland results in
decreased T-helper cell populations, and a
diminished mediation of the specific-immune
response.
– There is a resulting decreased B-cell response and
decreased number of T-cytotoxic cells.
• Compromised immune function with age
results in increased titers of autoantibodies and
an increased incidence of cancer (both
contribute to overall mortality rates.)
End of Chapter 22
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