Introduction to the immune system

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Introduction to the immune system Innate
immunity the front line of defense non
specific Acquired immunity mechanisms- antigen
specificity immunological memory principles of
vaccination
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Important features of the immune system Must be
able to distinguish foreign antigens from self
antigens (what is an antigen?) Must have memory
(responds slowly to first exposure, but more
rapidly to subsequent exposures TO THE SAME
ANTIGEN)
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What does the immune system actually
do? Phagocytes- kill and remove foreign
or damaged cells Antibodies- tag invading
cells or viruses for destruction Cytotoxic
cells- killed altered cells Regulate the immune
response
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What/where is the immune system? Barriers Circul
ating blood cells Tissue-fixed cells Lymphatic
system
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p. 375, physical barriers to infection
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p. 377, origin of lymphoid cells
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Cells with immune function (p. 378) Granulocytes N
eutrophils most common leukocyte (50-70) most
potent phagocyte Eosinophils (2-4) probably
phagocytic involved in allergic responses,
parasitic infections Basophils (0-1) mostly
found in tissues (mast cells) release
inflammatory molecules
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Agranulocytes Monocytes (5-10) more common in
tissues In tissues macrophages- phagocytes
help regulate immune response (antigen
presenting cells) dendritic cells- present
antigen to lymphocytes Lymphocytes (20-40) B
cells- make antibodies T cells- some are
cytotoxic, some are regulatory
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Where are the lymphoid cells? In the blood In
the tissues In the lymphoid system Can be
recruited to site of injury or infection
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p. 396, the lymphoid system
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The lymphoid system parallels the
circulatory system Primary lymphoid organs-
where lymphoid cells develop bone marrow (ALL
blood cells) thymus- T cells mature there
(become cytotoxic or helper T cells) and
then circulate
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Secondary lymphoid organs Purpose to trap
antigen and present it to lymphocytes Most
lymphocytes actually reside in these
tissues Lymph nodes- filter antigen from
lymph Spleen- filters antigen from
blood Lymphoid tissue in mucosa, gut and skin
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Innate defenses If they are non-specific how
are they actually activated-appropriately?? Bar
riers skin antimicrobial chemicals lysozyme
(in tears and saliva stomach acid oxygen
metabolites normal flora (healthy competition)
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If barrier is breached- then what? Pattern
recognition- something is perceived
as abnormal Damaged tissue Structures
associated with bacteria (peptidoglycan, LPS,
etc.) toll-like receptors on phagocytes,
endothelial cells- some recognizes viruses,
too Cell is then activated in response
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Toll-like receptors, p. 381
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Complement proteins- circulate in blood Are
normally inactive, but become active when
binding to antigen, or antigen-antibody
complexes What happens next? A series of
reactions, resulting in destruction of
antigen inflammation enhanced phagocytosis of
antigen
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Complement system, p. 382
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Phagocytosis how do the cells know whence
to engulf? detectors of microbes and/or
damaged cells (pattern recognition) response
to cytokines (produced by damaged cells and
other immune cells complement receptors What
happens in phagocytosis?
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Process of phagocytosis, p. 384
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Neutrophils are more potent killers, but die
quickly Macrophages can present antigen
amplify immune response can prolong activity by
regenerating lysosomes Both contribute to
inflammatory response to infection and/or damage
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What is the inflammatory process? What triggers
the inflammatory process? What are the outcomes
of inflammation? What is apoptosis, and how does
it prevent inflammation?
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Inflammatory process, p. 387
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Inflammation is triggered by infection or
injury Purpose to contain damage (and
response) repair damage Cardinal signs of
inflammation swelling, redness, heat, pain
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Why swelling? Chemical signals are released by
damaged tissue Neutrophils, monocytes recruited
to the site and enter tissues fluid enters
tissues, too Why redness? Chemicals promote
vasodilation Blood vessel walls relax more
blood (and therefore more blood cells) can
be brought to the region
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Why heat? Chemicals raise temperature at the
spot (pyrogens) Increased temperature kills
microbes phagocytes are more active more
cells are formed Effect can be systemic
(fever) Why pain? Chemicals effect free nerve
endings (pain receptors) Pain inhibits
mobility can help localize damage
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Inflammation can cause a lot of
bystander damage Ideally, damaged is confined
to the site of injury Some sites are more
sensitive to damage than others Damage can be
systemic (septic shock, due to blood infections
loss of blood volume, tissue damage, excess clot
formation
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Not all cell death causes inflammation Apoptosis
programmed cell death Under genetic
control (In immune response a large number of
cells are formed to fight the infection- what
happens to them after the infection is cleared?)
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Summary Innate defense consists of barriers,
phagocyte surveillance, and mechanisms to
detect infection or damage Inflammation is the
first line response to infection Lymphocytes may
be activated during this process which will
respond more rapidly and inten- sively to
subsequent infections
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Adaptive immunity Specificity Memory Distinguishe
s self from non-self Components of adaptive
immunity Humoral Cell-mediated Principles of
vaccination Immune deficiency and its consequences
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Adaptive immunity takes several days to develop
(to first exposure to antigen) Cells
proliferate Antibodies are produced Cytokines
(signaling molecules) are produced Meanwhile,
innate mechanisms act Adaptive mechanisms
respond if infection has not been eliminated
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What are the adaptive mechanisms? Humoral
immunity against extracellular antigens
(bacteria, free viruses, toxins,
etc.) antibodies and other molecules Cell-mediat
ed against intracellular antigens (virus-infect
ed cells tumor cells) Responses are
orchestrated by helper T cells
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p. 395 (be sure to come back to this slide)
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How does humoral immunity work? B cells
proliferate (in lymphatic tissues) and make
antibodies Antibodies circulate and bind to
antigen Neutralization immobilization Immune
complexes Facilitates phagocytosis Facilitates
complement-mediated lysis B cells are activated
clonally
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p. 401 How antibodies work
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Clonal selection theory
In bone marrow
In the system
Applies to T cells, too (p. 403)
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Antibodies have certain features in common but
different classes (isotypes) have different
properties.
p. 398
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Variable region is unique, because each binds to
a different antigen Constant regions fall into
five classes (table 16.1, p. 399)
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What happens in the primary response that leads
to antibody production? T cells respond to
antigen produce cytokines These cause B cells
to proliferate and become plasma cells
(antibody-producing cells) They become more able
to react with antigen Class-switching (for
appropriate response) from IgM to IgA, IgG, IgE
(unclear about IgD) Memory cells- more of them
they respond faster in subsequent responses
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p. 405
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What about the memory cells?

• There are more of them in the circulation
• Antigen specificity does not change
• They have already gone through development so can
  become active right away (note the secondary
  response on previous slide)
• Both T and B memory cells have been identified
• Memory cells can live for years

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T cells also have an antigen-specific
receptor Receptor is NOT released T cell must
come in direct contact with antigen- presenting
cell Major antigen-presenting cells macrophage
dendritic cell B cell How do these cells
present antigen (and where)?
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What are the different types of T
cells CD4(helper) and CD8 (cytotoxic) Both have
antigen-specific receptors CD4 and CD8 molecules
help with antigen presentation CD4 cells see
antigen MHC Class II (helper T cells) CD8
cells see antigen MHC Class I (cytotoxic T
cells)
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What is MHC? (major histocompatibility complex)
Groups of cell- surface proteins, inherited When
cells process antigen they return
fragments (peptides) to the surface, bound to
either MHC Class I or Class II MHC Class I is
found on most cells MHC Class II on
antigen-presenting cells (and levels can vary)
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How do cells present antigen? Class II-bearing
cells take up and process antigen, then
antigen is expressed on cell surface bound to
MHC Class II Remember, only certain cell types
express MHC Class II- so not all cells can do
this Lots of antigen-presenting cells in lymphoid
tissues! Class I-bearing cells (remember,
virtually all cells), if infected or transformed,
will express antigen bound to MHC Class I
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When T cells are activated they proliferate and
produce cytokines Dozens of cytokines have been
identified (and other cells can produce them,
too) Cytokines bind to neighboring cells and
activate them Recall that immune response is
characterized by rapid proliferation and
activation of cells! (And you dont want cells
activated all the time)
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What do T cells actually do? T helper cells-
cytokine production (Some are engaged in
delayed-type hypersen- sitivity) Cytotoxic T
cells- cause apoptosis in targets What about
natural killer cells? similar targets as
CTLs no antigen-specific receptor no memory
response have antibody receptors probably
immune surveillance
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Natural killer cells vs cytotoxic T cells

• Natural killer cells part of innate immune system
• Early protection against transformed cells or
  virus-infected cells (Same targets as cytotoxic T
  cells)
• Cytotoxic T cells become activated if natural
  killer cells cannot eliminate these cells

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How DO immune cells avoid reacting with self
antigens? Remember that T cells regulate the
immune response Most self-reactive cells are
eliminated in the thymus Antigen-presenting
cells seem to be key
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APC antigen presenting cell
Model of antigen presentation Notice the APC has
MHC Class II and other molecules required to
present antigen
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Summary, p. 412
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Immune system responds to antigens that enter
body in course of infection Vaccination
antigens are DELIBERATELY introduced to body to
generate a specific immune response (and
memory) Immune system normally distinguishes
harmful antigens from self antigens or
harmless substances What happens if it does
not? What happens if immune system is deficient?