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Reference: The Immunological Basis for Immunization Series, Module 1: General Immunology. WHO/EPI/GEN/93.11. 2
Specific Immune Response
• “Specific immune defense systems are not effective fully at birth and require
time to develop after exposure to the infecting agent or its antigens. Specific
immunity may be acquired naturally by infection or artificially by
immunization”.
Reference: The Immunological Basis for Immunization Series, Module 1: General Immunology. WHO/EPI/GEN/93.11.
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Types of Specific Immune Response
• Specific immune response is divided into:
• Antibody-mediated Immune response/ Humoral Immunity
• Cell-mediated Immune response
Reference: The Immunological Basis for Immunization Series, Module 1: General Immunology. WHO/EPI/GEN/93.11.
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Humoral immunity
• “This is the type of immunity in which antibody plays the most
important role. B cells are involved which differentiate into plasma
cells which can excrete antibody. B cells need the help of
macrophages, T cells, and sometimes complement in order to destroy
foreign invaders”.
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Types of Humoral Immunity
• There are two types of humoral immunity:
1. Active immunity
2. Passive immunity
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Active Immunity
• In active immunity the person actively makes an antibody after exposure to a
foreign antigen.
• Active immunity can be artificial (e.g., following vaccination with a live or
attenuated virus), or natural (e.g., following exposure to a disease-causing
organism, infection).
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https://sites.ualberta.ca/~pletendr/tm-modules/immunology/70imm-humoral.html#:~:text=Humoral immunity can be subdivided,exposure to a foreign antigen.
Passive Immunity
• In passive immunity a person is given an antibody that has been made by
someone else.
• It can be artificial (e.g., gamma globulin given to people with a
gammaglobulinemia) or natural (e.g., maternal antibody that has crossed the
placenta into the fetus).
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Antibodies
• Proteins that recognize and bind to a particular antigen with very high
specificity.
• Produce in response to exposure to the antigen.
• One virus or microbe may have several antigenic determinant sites, to
which different antibodies may bind.
• Each antibody has at least two identical sites that bind antigen: Antigen
binding sites.
• Belong to a group of serum proteins called immunoglobulins (Igs).
Schroeder, H. W., Jr., & Cavacini, L. (2010). Structure and function of immunoglobulins. The Journal of allergy and clinical immunology, 125(2 Suppl 2), S41-S52. https://doi.org/10.1016/j.jaci.2009.09.046
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Functions of Antibodies
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Immunoglobulins
• Specialized group of proteins mostly associated with γ globulin fraction.
• Immunoglobulins is a functional term while γ globulin is a physical term.
• Abbreviated as Ig.
• Ig are produced by plasma cells in response to an antigen and which function
as antibodies.
Schroeder, H. W., Jr., & Cavacini, L. (2010). Structure and function of immunoglobulins. The Journal of allergy and clinical immunology, 125(2 Suppl 2), S41-S52. https://doi.org/10.1016/j.jaci.2009.09.046 12
Major functions of Immunoglobulins
Main antibody in the secondary response.
Opsonizes bacteria, making them easier to phagocytose.
Fixes complement, which enhances bacterial killing.
IgG Neutralizes bacterial toxins and viruses.
Crosses the placenta.
Moura, R., Agua-Doce, A., Weinmann, P., Graça, L., & Fonseca, J. (2008). B cells: From the bench to the clinical practice. Acta reumatológica portuguesa, 33, 137-154.
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IgM Produced in the primary response to an antigen.
Fixes complement.
Does not cross the placenta.
IgD Found on the surfaces of B cells where it acts as a receptor for antigen.
Moura, R., Agua-Doce, A., Weinmann, P., Graça, L., & Fonseca, J. (2008). B cells: From the bench to the clinical practice. Acta reumatológica portuguesa, 33, 137-154.
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Mechanism of humoral immunity
1. Primary response
2. Secondary response
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Humoral (antibody-mediated) Immunity
Memory
Cells
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Phases of the Humoral Immune Response
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Primary and Secondary Humoral Responses
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In a primary immune response, naïve B cells are
stimulated by antigen, become activated, and differentiate
into antibody-secreting cells that produce antibodies
specific for the eliciting antigen.
A secondary immune response is elicited when the same
antigen stimulates memory B cells, leading to production
of greater quantities of specific antibody than are
produced in the primary response.
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Cell-mediated immunity
“Cell-mediated immunity (CMI) is an immune response that does not involve
antibodies but rather involves the activation of macrophages and NK-cells,
the production of antigen-specific cytotoxic T-lymphocytes, and the release
of various cytokines in response to an antigen.”
Cell-Mediated Immunity - An Overview. (2021, January 4). Retrieved April 22, 2021, from https://bio.libretexts.org/@go/page/3326 21
• Activated macrophages: These cells exhibit enhanced killing of
intracellular microorganisms, increased secretion of cytokines and
mediators, and higher expression of co-stimulatory molecules.
• NK-cells: Natural killer (NK) cells are innate immune cells that show strong
cytolytic function against physiologically stressed cells such as tumor cells.
Mosser, D. M., & Edwards, J. P. (2008). Exploring the full spectrum of macrophage activation. Nature reviews. Immunology, 8(12), 958–969. https://doi.org/10.1038/nri2448
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Paul S, Lal G. The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Frontiers in Immunology. 2017;8(1124).
Kerkvliet N, Lawrence BP. 5.05 - Cytotoxic T Cells*. In: McQueen CA, editor. Comprehensive Toxicology (Second Edition). Oxford: Elsevier; 2010. p. 109-32.
Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37. https://doi.org/10.1097/AIA.0b013e318034194e
Mechanism of action
1. Activating
antigen-specific cytotoxic T-lymphocytes (CTLs) that are able to destroy
body cells displaying epitopes of foreign antigen on their surface, such as virus-
infected cells, cells with intracellular bacteria, and cancer cells displaying tumor
antigens;
2. Activatingmacrophages and NK cells, enabling them to destroy intracellular
pathogens; and
3. Stimulatingcells to secrete a variety of cytokines that influence the function of other
cells involved in adaptive immune responses and innate immune responses.
It is most effective in destroying virus-infected cells, intracellular bacteria, and cancers. It also
plays a major role in delayed transplant rejection.
Cell-Mediated Immunity - An Overview. (2021, January 4). Retrieved April 22, 2021, from https://bio.libretexts.org/@go/page/3326 23
• Memory T cells are antigen-specific T
cells that remain long-term after an infection
has been eliminated. The memory T cells are
quickly converted into large numbers of
effector T cells upon preexposure to the
specific invading antigen, thus providing a rapid
response to past infection.
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Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the
Cell. 4th edition. New York: Garland Science; 2002. T Cells and
MHC Proteins.
• T-lymphocytes are able to randomly cut out and splice together different
combinations of genes along their chromosomes through a process
called gene translocation. This is known as combinatorial diversity and
results in each T-lymphocyte generating a unique T-cell receptor (TCR).
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Cell-Mediated Immunity - An Overview. (2021, January 4). Retrieved April 22, 2021, from https://bio.libretexts.org/@go/page/3326
• As a result of combinatorial diversity and junctional diversity, each T-
lymphocyte is able to produce a unique shaped T-cell receptor
(TCR) capable of reacting with complementary-shaped peptide
bound to a MHC molecule.
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Cell-Mediated Immunity - An Overview. (2021, January 4). Retrieved April 22, 2021, from https://bio.libretexts.org/@go/page/3326
• When an antigen encounters the immune system, epitopes from protein
antigens bound to MHC molecules eventually will react with a naive T-
lymphocyte with TCRs and molecules on its surface that more or less fit
and this activates that T-lymphocyte. This process is known as clonal
selection.
Cell-Mediated Immunity - An Overview. (2021, January 4). Retrieved April 22, 2021, from https://bio.libretexts.org/@go/page/3326 27
Life-style factors affecting immune function
Maggini S, Pierre A, Calder PC. Immune Function and Micronutrient Requirements Change over the Life Course. Nutrients. 2018;10(10):1531. Published 2018 Oct 17. doi:10.3390/nu10101531
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