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IMMUNE SYSTEM
 Protects the host from pathogens
 Minimizes self-tissue damage
 Types and components:
Anatomical
barriers
Phagocytes
Cytokines
Innate
Complement
Mast
Basophils
Immune
System
Natural killer
cells
humoral
B
lymphocytes
antibody
cellular
T
lymphocytes
cytokines
Adaptive
Types:
I-Innate immune system
 Non-specific defenses against infection
 Provides immediate protection against an invading pathogen
 Includes:
1. Anatomical barriers:
 Skin:
 Physiological factors: as sebaceous glands
 Sweat.
 Mucous membranes of the respiratory, gastrointestinal and
genitourinary tract.
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 Endogenous commensal bacteria
2. Phagocytes:
 Specialized cells
 Ingest and kill microorganisms, scavenge cellular and infectious debris,
and produce inflammatory molecules which regulate other components
of the immune system.
 Crucial for defense against bacterial and fungal infections
 Include:
a) Neutrophils (polymorphonuclear leucocytes)
 Derived from the bone marrow and circulate freely in the blood
 Short half-life of 6 hours
 Functions:
1. kill microorganisms directly
2. facilitate the rapid transit of cells through tissues
3. non-specifically amplify the immune response
b) Monocytes and macrophages
 Monocytes are the precursors of tissue macrophages
 Produced in the bone marrow and exported to the circulation
 After 7-10 hours in the blood stream, they migrate to peripheral tissues
where they differentiate into tissue macrophages and reside for long
periods
 Specialized populations of tissue macrophages include Küpffer cells in
the liver, alveolar macrophages in the lung, mesangial cells in the
kidney, and microglial cells in the brain
 Functions:
1. Initiation and amplification of the inflammatory response
2. Killing of microorganisms
3. Resolution and repair of inflammation
4. Link between innate and adaptive immune system
3. Cytokines:
 Small soluble proteins
 Act as multipurpose chemical messengers
 Produced by cells involved in innate and adaptive immune responses and
by stromal tissue
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4. Complement
 A group of more than 20 tightly regulated, functionally linked proteins
 Promote inflammation and eliminate invading pathogens
 Produced by the liver
 Present in the circulation as inactive molecules.
 Pathway:
a. The alternative pathway is directly triggered by binding of C3 to
bacterial cell wall.
b. The classical pathway is initiated when IgM or IgG antibody binds to
antigen, forming immune complexes.
c. The lectin pathway is activated by the direct binding of mannosebinding lectin to microbial cell surface carbohydrates
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Functions:
1. Defense against encapsulated bacteria such as Neisseria spp. and
Haemophilus influenza
2. Act as opsonins, rendering microorganisms more susceptible to
phagocytosis by macrophages and neutrophils
3. Chemotactic agents: promoting leucocyte trafficking to sites of
inflammation
4. Some fragments act as anaphylotoxins, binding to complement
receptors on mast cells and triggering release of histamine, which
increases vascular permeability
5. Target immune complexes to antigen-presenting cells, providing a
link between the innate and the acquired immune systems
6. Dissolve the immune complexes that triggered the cascade,
minimising bystander damage to surrounding tissues.
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5. Mast cells and Basophils:
 Are bone marrow-derived cells
 Play a central role in allergic disorders
 Mast cells reside predominantly in tissues exposed to the external
environment, such as the skin and gut
 Basophiles are located in the circulation and are recruited into tissues
in response to inflammation
 Both contain large cytoplasmic granules which enclose preformed
vasoactive substances such as histamine. Additional mediators are
synthesised de novo after activation, including leukotrienes,
prostaglandins and cytokines
6. Natural killer cells:
 Large granular lymphocytes
 Play a major role in defense against tumours and virally infected cells
 Express features of both the adaptive and innate immune systems
 Morphologically similar to lymphocytes and recognise similar ligands,
but they are not antigen-specific and cannot generate immunological
memory
 Express a variety of cell surface receptors
 stress signals
 absence of HLA molecules on the surface
 binding of antigen-bound IgG antibody to surface receptors.
II. Adaptive immune system:
 Has exquisite specificity
 Highly adaptive, takes more time to develop but confers long-lasting
protection.
 Possesses immunological memory
 Types:
1. humoral immunity: produced by B lymphocytes, mediated by
antibody
2. cellular immunity: mediated by T lymphocytes, which synthesise
and release cytokines that affect other cells.
1. Humeral immunity
-B-lymphocyte:
 Specialized cells arise from haemopoietic bone marrow stem cells
 Major function is to produce antibody
 Mature B lymphocytes can be found in the bone marrow, lymphoid
tissue, spleen, and to a lesser extent the blood stream
 Express a unique immunoglobulin receptor on their cell surface (the Bcell receptor), which binds to soluble antigen
IMMUNE SYSTEM
- Immunoglobulin:
 Soluble proteins made up of two heavy and two light chains
 The heavy chain determines the antibody class or isotype, i.e. IgG, IgA,
IgM, IgE, IgD
 Subclasses of IgG ( IgG1,2,3,4) and IgA(IgA1,2) also occur
- Antibody Function:
 Facilitate phagocytosis by acting as opsonins
 Facilitates cell killing by cytotoxic cells, particularly natural killer
cells
 Trigger activation of the classical complement pathway
 May act directly to neutralise the biological activity of their antigen
target.
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2. Cellular immunity:
 T lymphocytes mediate cellular immunity
 Function:
1) Defense against viruses, fungi and intracellular bacteria.
2) Immunoregulatory role
 Leucocyte cell surface molecules are named by differentiation (CD)
antigen number
 T lymphocyte type:
1) CD8+ ('cytotoxic') T lymphocytes
 Specialized cells
 Recognize antigenic peptides in association with HLA class
I (HLA-A, HLA-B, HLA-C)
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 Kill infected cells directly through the production of poreforming molecules such as perforin, or by triggering
apoptosis of the target cell
 Secrete cytokines such as IFN-γ which have antiviral
activity
+
2) CD4 ('helper') T lymphocytes:
 Recognize peptides presented on HLA class II molecules
(HLA-DR, HLA-DP and HLA-DQ)
 Have immunoregulatory functions
 Produce cytokines and provide co-stimulatory signals that
support the activation of CD8+ T lymphocytes and assist the
production of mature antibody by B cells
 Interact closely with phagocytes which determine cytokine
production by both cell types.
 CD4+ lymphocytes can be subdivided into:
1) Th1 cells:
 Produce IL-2, IFN-γ and TNF-α
 Support the development of delayed type
hypersensitivity responses
2) Th2 cells:
 Secrete IL-4, IL-5 and IL-10
 Promote allergic responses
3) Regulatory cells:
 Regulate other CD4+ cells
 Prevent autoimmune disease.