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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

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specific immune response
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

specific immune response3
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
specific immune response4
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 APC’s 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

APC’s after binding to Helper T cells.

specific immune response5
Specific Immune Response

Figure 20-10 Vander et al, 8th Ed.

specific immune response6
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 APC’s after binding to Helper T cells.

Th2 cell production is stimulated by IL-4 (Interleukin-4) from Th0 cells.

specific immune response7
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.

specific immune response8
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
  • 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.
specific immune response12
Specific Immune Response

Effector Phase

Antibody-Mediated (Humoral) Response

Abs are immunoglobulins (Ig’s) that have 2 functions:

1. Recognize and interact specifically with foreign Ag’s.

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 Ab’s to recognize
  • specific Ag’s.
  • Remember 5 classes of Ig’s: IgA, IgD, IgE, IgG and IgM
  • Ab’s improve the host’s ability to recover from an invading Ag associated with
  • a virus or a bacterial toxin.
  • Ab’s interact with elements of the innate immune system as follows:
    • Activate Complement
    • Stimulate Ingestion of Bacteria
    • Assist Cytotoxic Cell Function
    • Stimulate Allergic Reactions
specific immune response14
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.

Complement-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.

specific immune response16
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.
specific immune response17
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.