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Transcript
Dr. Fadwah Al-Ghalib
Basic Immunology
2nd Year 2009
The Innate Immunity
(Natural Immunity)
The body has two types of response to invasion by a pathogen:
1- The innate immune response ( natural or non-specific)
2- The adaptive immune response (acquired- Specific).
The Natural Immunity is the first immunological non specific barrier
to fight against
infections without previous immunization, in other words is the immediate ability of a host
organism to prevent or control an infectious challenge.
This is the immunity one is born with and is the initial response by the body to eliminate
microbes and prevent infection.
This innate response is produced in a few minutes or hours after the aggression, and is
mediated by phagocytic cells, natural killer cells (NK) and interferon.
When this first barrier fails, the infection is established, and the adaptive immunity starts to
develop. In the innate response, the most important humoral mechanism is the complement.
The most important mechanism of the cellular response during the innate response is the
activation of macrophages and NK cells.
The innate immune responses involve:
 phagocytic cells (neutrophils, monocytes, and macrophages);
 cells that release inflammatory mediators (basophils, mast cells, and eosinophils);
 natural killer cells (NK cells); and
 molecules such as complement proteins, acute phase proteins, and cytokines.
Major Cells of Innate Immune System
a) Neutrophil: (Phagocytosis, and bacteriocidal mechanisms)
b) Eosinophil: ( For killing parasites)
c) Macrophage: (Phagocytosis, bacteriocidal mechanisms, antigen presentation)
d) Mast cells: (in tissues) [ release histamine and other mediators]
e) Natural killer cells: (lyses of some virally infected cells)
Properties of the Natural Immunity:
1- They are present at birth
2- Can rapidly brought into action
3- Do not always have power to eliminate the infection.
4- Do not lead to long-term immunity to the particular pathogen ( do not develop
memory).
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Dr. Fadwah Al-Ghalib
Basic Immunology
2nd Year 2009
Natural immunity (innate immunity) include some barriers:
1) Physical Barriers:
a) Skin
b) Mucous membranes
c) Eyes
2) Mechanical Barriers
3) Biological Barriers:
a) Commensal microbes
1- Physical Barriers (Anatomical barrier):
a) skin: is the first human body’s first defence against infection. This barrier can be
breached by physical damage ( wounds, burns, surgical procedures, pimples, and
fungal infection).
1-pH:
 Most pathogens are very sensitive to acidic environment, an acid pH less than 6 inhibits
the growth of potential pathogens.
 the skin has a pH of 5.5
2- Microcidal molecules: (Biochemical substances)
i.
-defensin, -defensin, and cathelicidin = inhibit microbial growth by damaging the
microbial membranes and causing lysis
ii.
RNases, DNases : act on RNA & DNA of the microbes.
iii.
Fatty acids: released from commensal microbes (present on skin)inhibit growth of
bacteria
iv.
Sweat glands contains:
-
v.
lysozyme breaks down peptidoglycan.
Transferrin and lactoferrin deprive organisms of iron.
Evaporation of the sweat glands
creates salty
environment that inhibits growth of many bacteria.
The skin, consisting of the epidermis and the dermis, is dry, acidic, and has a
temperature lower than 37 degrees Celsius (body temperature). These conditions are not
favorable to bacterial growth.
vi.
Resident normal flora of the skin also inhibit potentially harmful microbes.
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Dr. Fadwah Al-Ghalib
vii.
Basic Immunology
2nd Year 2009
In addition, the dead, keratinized cells that make up the surface of the skin are
continuously being sloughed off so that microbes that do colonize these cells are
constantly being removed.
viii.
Hair follicles and sweat glands produce lysozyme and toxic lipids that can kill bacteria.
ix.
Finally, beneath the skin surface is skin-associated lymphoid tissue (SALT) that
contains cells for killing microbes and sampling antigens on the skin to start adaptive
immune responses against them.
b. the mucous membranes:
Mucous membranes line body cavities that open to the exterior, such as the respiratory tract,
the gastrointestinal tract, and the genitourinary tract. The mucus is a physical barrier that traps
microbes.
Mucus contains:
a. lysozyme to degrade bacterial peptidoglycan,
b. antibody called secretory IgA that prevents microbes from attaching to mucosal
cells and traps them in the mucous,
c. lactoferrin to bind iron and keep it from being used by microbes
d. lactoperoxidase to generate toxic superoxide radicals that kill microbes.
e. Resident normal flora of the mucosa also inhibit potentially harmful microbes.
In addition, the mucous membrane, like the skin, is constantly sloughing cells to
remove microbes that have attached to the mucous membranes.
f. Beneath the mucosal membrane is mucosa-associated lymphoid tissue (MALT)
that contains cells for killing microbes and sampling antigens on the mucosa to
start adaptive immune responses against them.
1) Physical Barrier /
b-Mucus Membrane:
i) Respiratory tract:
a- Respiratory epithelium secretes -defensin attach to microbes and make them more
susceptible to ingestion and destruction by phagocytic cells.
b- Nose hairs and cilia help moving the secretions containing trapped microbes, outwards for
expulsion by coughing and sneezing.
3
Dr. Fadwah Al-Ghalib
Basic Immunology
2nd Year 2009
ii) Gastrointestinal tract: (GIT)
-Low pH( 1.0-3.0) of the Stomach
-Some epithelial cells secrete microcidal molecules:
- (-defensins and cryptidin) help to destroy pathogens.
-22 different digestive enzymes are secreted from salivary glands, stomach, and
small intestines.
-Lysozymes, and Secretary IgA, are found in saliva, are effective in killing
pathogens.
iii) Urogenital Tract:
-Normally the urine is sterile, it flushes out the organisms if they ascend through the
urethera.
-Kidneys produce antibacterial peptide -defensin-1, limits ascending infection.
- Similar peptides are produced in the vagina, cervix, and uterus.
- normal Vaginal pH (4.4-4.6)
1) Physical Barrier
The EYES:
-Lacrimal glands produce tears.
-These glands contains lysozyme enzyme that cleave the peptidoglycan of Grampositive bacteria, and the chitin of the fungi.
2- Mechanical removal is the process of physically flushing microbes from the body. Methods
include:
a. The cough and sneeze reflex
b. vomiting and diarrhea
c. the physical flushing action of body fluids (Fluids such as urine, tears, saliva,
perspiration, and blood from injured blood vessels also flush microbes from the
body.
3- Biological Barriers
Commesal Microbes:
a. Are microbes that exist in symbiotic relationship with the body.
b. In GIT these microbes also assist in digestive process.
c. Any disruption of the normal flora can cause disease.
d. Use of antibiotics reduces the levels of commensal bacteria in the GIT.
3- Cellular Components: Combative phagocytic & cytotoxic cells
1.
B lymphocyte response
a.
Some divide to produce pool of cells specific for this antigen
b.
Some differentiate to produce plasma cells that secrete antibody in large quantity
c.
Antibody produced is specific for bacterial antigen that provoked the response
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Dr. Fadwah Al-Ghalib
Basic Immunology
2nd Year 2009
d.
Antibody binds to bacterial antigen, lableling the bacteria as targets for destruction
2.
T lymphocyte response
a.
Some T-helper cells divide to produce pool of cells specific for this antigen
b.
Some T-helper cells send signals to activate cytotoxic T cells
c.
Cytotoxic T cells kill target cells expressing foreign antigen
CLONE
 is a lymphocyte population committed to a certain antigen.
 It is considered there are dozens million B-cell clones and T-cell clones in each human
organism.
 A committed lymphocyte involved in immune response becomes primed lymphocyte
CLONAL SELECTION THEORY
 Each of us has a large heterogenous population of lymphocytes.
 Each of which is capable of binding antigens of a single specificity.
 If a proper antigen binds to that specific receptor, the cell can come :
1-activated
2-undergo division 3-forming plasma cells. 4-& produce a clone of
antibody.
This model is known as the clonal selection theory.
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