Specific Immune Response

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Specific Immune Response
Reading Rang et al, Chapter 12, Local Hormones,
Inflammation Allergy The key cells involved in
the specific immunological response are
LYMPHOCYTES, falling into 3 main groups 1. B
Cells responsible for antibody (Ab)
production 2. T Cells important in the Induction
Phase and responsible for cell-mediated
response 3. NK Cells Natural Killer Cells,
specialised non-T, non-B cells that are
activated in the innate response In the
specific immune response there are 2 main
phases 1. Induction Phase 2. Effector
phase This is further subdivided
into 2a. Humoral Component (Antibody-mediated)
2b. Cell-mediated Component
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Specific Immune Response
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Specific Immune Response

• Induction Phase
• This involves the activation of T cells and B
  cells when a foreign antigen (Ag)
• is presented to a naïve Helper T Cell by an
  Antigen Presenting Cell (APC).
• Remember
• Antigen
• any foreign compound that initiates an immune
  response
• usually a protein or polysaccharide
• often found on the surface of microorganisms,
  transplanted
• tissues/organs, foods etc.
• Antibody
• specifically produced to neutralise ONE type of
  Antigen.
• Produced by B cells
• blueprint is kept by Memory T cells

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Specific Immune Response
Induction Phase Antigens reach the local lymph
nodes via the lymphatics. The antigen is
presented to lymphocytes by Antigen Presenting
Cells. The APCs ingest and process the Ag and
present it to an uncommitted or naïve
CD4-positive Helper T cell in conjunction with
the MHC. These naïve Helper T Cells begin to
produce Interleukin-2-receptors as well
as generating Interleukin-2. Interleukin-2 is a
cytokine that has an autocrine function, that is,
it causes the proliferation of activated Helper T
Cells which are now called Th0 cells. Th0 cells
then produce either Th1 or Th2 cells Th2 cell
production is stimulated by IL-4 (Interleukin-4)
from Th0 cells. Th1 cell production is
stimulated by IK-12 (Interleukin-12) secreted
from the APCs after binding to Helper T cells.
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Specific Immune Response
Figure 20-10 Vander et al, 8th Ed.
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Specific Immune Response
These naïve Helper T Cells begin to produce
Interleukin-2-receptors as well as generating
Interleukin-2.
Interleukin-2 is a cytokine that has an autocrine
function, that is, it causes the proliferation of
activated Helper T Cells which are now called
Th0 cells.
Th0 cells then produce either Th1 or Th2 cells
Th1 cell production is stimulated by IK-12
(Interleukin-12) secreted from the APCs after
binding to Helper T cells.
Th2 cell production is stimulated by IL-4
(Interleukin-4) from Th0 cells.
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Specific Immune Response
Induction Phase
Th2 cells under the influence of IL-4
will promote the proliferation of B Cells which
are responsible for our Antibody mediated immune
responses. Some B Cells become Plasma Cells
and release Ab into blood. Memory B Cells that
retain the blueprint of the Ag for future Ab
production should the same Ag enter the body
later.
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Specific Immune Response
Induction Phase
Th1 cells produce several cytokines but mf
activating cytokines and Interferon g are most
important initially. Interferon g is responsible
for stimulating CD8 T Cells to become Cytotoxic T
Cells This is the beginning of the
cell-mediated pathway of the immune response.
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Specific Immune Response
Figure 12.3 Rang et al.
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Specific Immune Response
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Specific Immune Response

• Induction Phase Summary
• The 2 subsets of T Cells are important because
  they are responsible for
• providing the balance in response by the immune
  system.
• Also any dysfunction at this level will lead to
  deficiencies in both Ab-mediated
• and/or cell-mediated immunity.
• Th1 Cells and Cell-Mediated Immunity
• Th1Cells produce the cytokines (IL-2, TNF-b and
  IFN g) that
• activate macrophages
• stimulate CD8 lymphocytes to release IL-2
  yielding cytotoxic T cells
• inhibit Th2 cells by INFg action.
• Th2 Cells and Ab-Mediated Immunity
• Produce cytokines (IL-4, TGF-b, IL-10) that
• Stimulate B Cell proliferation (CD4 Cells)
• Stimulate differentiation of eosinophils
• Inhibit Th1 Cell function.

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Specific Immune Response
Effector Phase Antibody-Mediated (Humoral)
Response Abs are immunoglobulins (Igs) that
have 2 functions 1. Recognize and interact
specifically with foreign Ags. 2. Activate one
of more host defence mechanisms. Structure of
Antibodies Y - shaped proteins containing Fab
portion that has the recognition site for Ag Fc
portion that activates host defences.
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Specific Immune Response

• Effector Phase
• Among B cells there are clones that express
  individual Abs to recognize
• specific Ags.
• Remember 5 classes of Igs IgA, IgD, IgE, IgG
  and IgM
• Abs improve the hosts ability to recover from
  an invading Ag associated with
• a virus or a bacterial toxin.
• Abs interact with elements of the innate immune
  system as follows
• Activate Complement
• Stimulate Ingestion of Bacteria
• Assist Cytotoxic Cell Function
• Stimulate Allergic Reactions

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Specific Immune Response
Ab and Complement Ab binds to Ag forming an
Ag-Ab Complex. This exposes the Fc portion of the
Ab which is a binding site for Complement. Complem
ent-Fc Complex results in activation of the
complement sequence, particularly the Classical
Pathway. Ie. C3a anaphylatoxin C5a chemotaxic
factor C3b opsonin Leading to lysis of the
invading cell. Ab and Ingestion of
Bacteria Ag-Ab Complex, exposes Fc
portion Attracts phagocytic cells (neutrophils
and macrophages) Begins ingestion process.
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Specific Immune Response
Effector Phase Ab and Cellular Toxicity Ag-Ab
Complex allows cross-links between a parasite and
eosinophils. Eosinophils kill the
microorganism. Useful for large pathogens such as
protozoa and worms. Ab and Allergic
Reactions Mast Cells and Basophils have
receptors for IgE which can become attached to
the cell membrane. When Ag reacts with this
cell-fixed Ab it yields an enormous response with
the release of many inflammatory mediators.
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Specific Immune Response

• Effector Phase
• Cell-Mediated Response
• Lymphocytes involved are both
• CD8 (Cytotoxic T Cells) and
• Inflammatory, cytokine releasing Th1 Cells
  (CD4)
• Cytotoxic T Cells
• Attack virus-infected tissue cells in 2 steps
• 1. Recognition and signalling that the cell is
  infected.
• Expression on the cell surface of peptides
  derived from the pathogen
• in association with MHC protein.
• 2. Protein-MHC complex is recognized by CD8 T
  Cells which destroy
• virus-infected tissue cell.

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Specific Immune Response
Effector Phase Cytokine-Releasing Th1 Cells
(CD4) Their main role is to activate
macrophages. Some pathogens have evolved a
survival mechanism of multiplying
inside macrophages after being ingested. E.g.
Mycobacteria and Listeria An infected
Macrophage produces an Ag-MHC complex on its own
surface which is recognized by
cytokine-releasing Th1 cells. The cytokines
released by the Th1 cells help the macrophage to
kill the pathogen inside it. In all other
cases, Th1 cells activate macrophages to engulf,
ingest and digest the invading pathogen. In the
process an Ag is bound to MHC to present Ag to
the T Cells. What happens next depends on
whether Th1 or Th2 cells are stimulated.
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Specific Immune Response