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The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
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3. Immunology is the branch of biology concerned with the body's defense reactions.
In essence, the immune system exists to maintain the integrity of the body by
excluding or removing the threatening microorganisms which could invade from
the environment
There are two kinds of immunological defense:
1. natural or innate immunity,
comprising mainly pre-existing non-specific defenses
2. adaptive or acquired immunity, during which the immune system responds in
an antigen-specific manner to neutralize the threat efficiently, and retains a
memory of the threat so that any future encounter with the same threat will
result in an accelerated and heightened protective response.
4. 1st line of defense
2nd line of defense
1- Antibody-mediated: (Humoral immunity)
2- Cell-mediated immunity (CMI)
Specific immunity
Dr. Samir Bloukh
3ed line of defense
7. • THE INNATE IMMUNE SYSTEM
• These intrinsic defense mechanisms are present at birth prior to exposure to -
pathogens or other foreign macromolecules.
• They are:
- not enhanced by such exposures and are
- not specific to a particular pathogen.
• - Mechanical and chemical barriers
• Intact skin is usually impenetrable to microorganisms.
• Membranous linings of the body tracts are protected by mucus, acid secretions
etc
• In the lower respiratory tract, hair-like protrusions of the epithelial cell
membrane called cilia.
• saliva,
• tears
8. Phagocytosis
• Phagocytosis is a process by which phagocytic cells ingest
• extracellular material, including whole pathogenic microorganisms. If the mechanical
defences are breached, the phagocytic cells become the next barrier.
• These include:
• - polymorphonuclear leukocytes (polymorphs) (PMNL) and
• - macrophages. (tissue monocytes)
• Polymorphs are short-lived circulating cells which can invade the tissues
• Macrophages are tissue-resident stage of circulating monocytes. Macrophages are found
in areas of blood filtration where they are most likely to encounter foreign particles, e.g.
liver, kidney, alveoli, lymph nodes and spleen.
9. Natural killer cells
Natural killer (NK) cells are lymphocytes that account for up to 15% of blood lymphocytes and
have a special role in the killing of
- virus-infected cells and
- malignant cells
- killing antibody coated microorganisms
Acute-phase proteins
Serum proteins produced by the liver in response to tissue-damaging infections and other
inflammatory stimuli. It enhances the efficiency of innate immunity. The concentration of the
following acute-phase proteins in body fluids increases rapidly during tissue injury or infection
10. • • C-reactive protein can bind to bacteria and promote their removal by
phagocytosis. It is a major acute-phase protein, so named as it binds to the
polysaccharide cell wall component on a variety of bacteria and fungi
• - Interferon
• Interferon, produced by virus-infected cells, comprises a group of cytokines that
mediate innate immunity and includes those that protect against viral infection
11. Complement System:
A group of about 30 plasma proteins that are in inactivated form.
Mainly C1-C9. When complement cascade reaction is initiated, the
enzymatic activation of one component triggers activation of many of
the next and so on.
Complement system can be activated in 3 ways:
1. Alternative pathway
2. Classical pathway (Ag-Ab)
3. Mannose-binding lectin pathway
12. 1- The alternative pathway of complement activation can be
stimulated directly by microorganisms and is important in the
early stages of the infection before the production of antibody.
2- The classical pathway requires antibody, which may take weeks to develop.
Both pathways can lead to the lytic or Membrane Attack Complex (MAC).
During the course of complement activation, numerous split products of
complement components, with important biological effects, are produced.
3.Mannose-binding lectin pathway
13. • Biological effects of complement activation
• Probably the most important function of the complement system is to
• 1- opsonize antigen-antibody (immune) complexes, microorganisms and cell
debris for phagocytosis.
• 2- anaphylatoxins The peptides C3a, C4a and C5a are anaphylatoxins which cause
mast cell degranulation and smooth-muscle contraction. They increase vascular
permeability, which permits cells and fluids to enter the tissues from the
circulation.
• 3- Formation of MAC (membrane attack complex)
• Which will make a hole in the membrane of the e.g Bacteria or RBCs leading to
its death or lysis. Certain microorganisms, notably Gram-negative bacteria, can
be lysed directly by the (MAC) membrane attack complex.
• 4- Chemotaxis, (chemotactic factor) attracts phagocytes (C5a)
• 5- Phagocyte activation C3b
14. THE ADAPTIVE IMMUNE SYSTEM
The defense mechanisms in adaptive immunity can specifically recognize and
selectively eliminate pathogens and foreign macromolecules. Adaptive immune
responses are reactions to specific antigenic challenge and display four cardinal
features:
- specificity,
- diversity,
- immunologic memory and
- discrimination of self and non-self.
16. Adaptive immune responses are specific for distinct antigens. This unique
specificity exists because B and T lymphocytes express membrane receptors
that specifically recognize different antigens.
Importantly, adaptive immunity is not dependent on innate immunity.
Through delicately modulated interactions, the 2 types of defense mechanism
work synergistically to produce more effective immunity.
17. B lymphocytes
Plasma cells Antibodies
2000 Abs/second
Extracellular pathogens and Exotoxins
T lymphocytes (CD4 and CD8)
Effector lymphocytes (CD4 and CD8)
Intracellular pathogens:
Memory cells Memory cells
Dr. Samir Bloukh
18. IMPORTANT CELLS INVOLVED IN ADAPTIVE IMMUNITY
1- The Dendritic cell (APC): they are phagocytic cells which are mainly concerned with processing
and presentation of the Ags to the lymphocytes and so they are called the antigen presenting cells.
They can also secrete cytokines e.g. interleukin-1 to activate CD4 + T-lymphocyte
2- Lymphocytes: they originate from a stem cell in the bone marrow and they include:
a. T-lymphocytes or T-cells which mature in the microenvironment of the thymus. They are
responsible for the cell-mediated immunity. T-cells can be subdivided into:
a.1- Helper / inducer subsets (CD4 + cells)
a.2- Suppressor/cytotoxic subsets (CD8 + cells)
b. B-lymphotyctes: or B cells which mature in the bone marrow and they are responsible for the
humoral immunity.
19. The major events taking place in the specific immune response are:
1. Antigen processing and presentation:
The antigen, e.g macrophage takes up the foreign antigen and breaks it into small fragments, then
presents it to the receptor on the surface of the specific T-helper cell. The macrophage also
secretes IL-1 which activates the T-helper cell.
2. Activation of the T-helper cell:
It undergoes proliferation and differentiation and produces a number of cytokines which acts on
other cells of the immune system as T-cytotoxic cells, B-cells and macrophages causing their
proliferation and activation.
3. Activation of T-cytotoxic cells:
The activated T-cytotoxic cell then releases cytotoxins which kill the target cell e.g. virus-infected
cell, tumor cell. This represents the cellular or cell-mediated immune response.
Memory cells are also produced for future similar infection
20. 4. Activation of B cells and production of antibodies:
B-cells will undergo proliferation and differentiation into antibody producing plasma cells. These
will secrete antibodies. These antibodies can:
-
- lyse bacteria or prepare them for phagocytosis by osponisaton, they can
-
- neutralize toxins and can
- neutralize viruses rendering them non-infective.
Some activated B and T-cells become memory cells which can respond to subsequent
encounters with the same antigen.
21. ANTIBODIES:
Antibodies are immunoglobulins (Igs) formed in response to Ags and they
react specifically with them. Igs fall mainly in the gamma globulin fraction
of serum.
Structure of immunoglobulins:
There are five classes of Igs in man;
IgG, IgM, IgA, IgD and IgE.
22. IgG:
It consists of four polypeptide chains; 2 H and 2 L held by disulphide bridges. It is bivalent and
it forms 75% of all Igs in the serum. It is the only one which crosses the placenta. It fixes the
complement. IgG is the predominent Ab in the SECONDARY immune response.
IgM:
It consists of 5 units, joined together by the J.chain. IgM comprises about 7% of Igs in normal
human serum. IgM is the Ig which appears early in the specific PRIMARY immune response. It
fixes the complement.
IgA: the monomeric IgA is found in serum, forming 15% of the circulating Igs. The dimers are
fond in secretions: milk, tears, saliva, nasal and bronchial secretions, gastrointestinal secretion,
colostrum and urine.
IgE: it is found in trace amounts in normal serum. The level of IgE in the serum of allergic
individuals is high. It plays an important role in type I hypersensitivity. IgE level in serum is
increased very much in parasitic infections.
IgD: found in a small concentration in serum.
23. Rate of production of Abs:
Primary response: mainly IgM
If an Ag is injected for the first time in an animal, 7-12 days will lapse, before Abs can be
detected in the serum, then the level of Ab will rise slowly, to a low peak then it falls.
Secondary response: mainly IgG
If another injection 2Nd time of the same Ag is given, the level of Abs will rise to a higher
level (higher peak) and stays longer than the first time. This is due to the presence of
immunological memory. If a third injection is given, the same response will occur, but with
a higher peak. This can occur with additional injections. The Ab in the secondary immune
response is mainly IgG.
24. Figure. Primary and secondary immune responses
Upon initial antigen encounter, both humoral and cell mediated adaptive responses are of limited
intensity and duration (primary response). Subsequent exposures to antigen (secondary response) are
characterized by increased intensity and durations. Each epitope elicits a separate response
25. Acquired immunity (Specific Immunity):
May be active or passive and each may be
natural or artificial
1. Passive acquired immunity:
a) Passive A. natural immunity:
Immunity is temporary and it gives immediate protection as a result of receiving
preformed Abs, as the IgG antibodies passing transplacentally from the mother to the
foetus. Abs are also present in the colostrum. The natural immunity protects the baby for
4-6 months only.
b) The passive A. artificial: i.e. the administration of preformed Abs. (Anti-rabies)
2. Active acquired immunity:
a) A.A.Natural
The host actively produces the Abs, so they last longer than the ready made Abs.
(INFECTIONS or DISEASES)
b) A.A.Artificial: (Vaccination with live attenuated bacteria or virus)
26.
27. IMMUNOPATHOLOGY: (Hypersensitivity, autoimmunity, immuno-deficiency)
Hyper sensitivity (allergy)
An over reactive immune response to foreign agent resulting in damage to host tissues e.g:
hypersensitivity and graft rejection.
Classification:
Type I (Immediate hyper sensitivity) (Anaphylactic reaction)
When a person exposed to an allergen (Ag), IgE is formed and this can bind to mast cells and
basophils specially those in the bronchial tree.
In 2nd exposure to same allergen, it cross-bridges two IgE antibodies fixed to mast cells (IgE-
Ag-IgE Bridge) and simulates degranulation of these cells. Chemical mediators such as
Histamine and prostaglandins and other factors produced. These types of reactions can be
localized, respiratory or gastrointestinal related, systemic or associated with shock.
Immediate 5-30 minutes Delayed effect 8-12 hrs
28. Type II: Cytolytic (Cytotoxic) reactions: e.g: activation of complement and lysis of RBCs or platelets, which can
involve drugs (haptens) binding to RBCs and inducing antibodies against them. (NK cells, Phagocytes and
Complement)
This type involves, usually IgG or IgM.
Ag is either part of a tissue cell (Ag of ABO and Rh Ag) or
closely associated with a cell e.g. drug attached to cell wall.
Examples:
• Hemolytic anemias.
• Cytopenias (thrombocytopenia- neutropenia)
• Drug toxicities.
29. Type III : immune complex reaction: e.g. complement fixing Ag-Ab complexes (main IgG)
these are usually phagocytosed, but if the complexes are too small for phagocytosis, they
can attach to the basement membrane of blood vessels and trigger inflammation
vasculitis.
• 1- systemic (serum sickness)
Used to be due to giving animal-derived antisera eg. (Horse anti-Diphtheria). After 7-10 days, patients may
develop serum sickness. Symptoms: urticaria due to vasculitis, arthritis, carditis, lymphadenopathy. It is
self limiting disease , rapidly cleared by phagocytic cells.
• 2- local (Arthus reaction): (complement involvement)
This type results from acute immune complex vasculitis causing tissue necrosis. These complexes activate
complement to induce a painful localized edematous inflammatory lesion. Lesions range from necrotizing
vasculitis to sterile abscess. These may occurs in diabetics who have received many intradermal injections
of insulin.
30. Type IV: delayed hypersensitivity or cell-mediated
hypersensitivity:
Occurs in certain diseases as TB, leprosy,….
Usually after 48-72 hrs
Tuberculin test : when an individual previously infected
with tubercle bacilli is given an intradermal injection of a
protein extract of tubercle bacilli, after 48-72 hrs.
erythematous induration, (a red hard swelling:
granuloma) occurs