Transcript Sistem Keta - IGP355 – PATOFISIOLOGI PENYAKIT II

Sistem Ketahanan
Tubuh
dan Alergi
Patofisiologi Gizi
Pokok Bahasan
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pengertian sistem ketahanan tubuh,
mekanisme seluler dan humoral
mekanisme alergi dan
hipersensitivitas
alergi makanan
Immune System
Nonspecific Defenses
Specific Defenses
•Physical barriers
•Phagocytes
•Immunological surveillance
•Interferons
•Complement
•Inflammatory response
•Fever
Limfosit B
IgG
IgA
IgM
IgD
IgE
Limfosit T
Th
(Th1&Th2)
Ts
Tdh
Tc
Physical Barriers
Epidermal epithelium
 multiple layers of dead,
keratinized cells and a network
of desmosomes locking the
cells together  prevent
pathogen entry.
 secretions such as sweat (the
low pH of which is
bacteriostatic) and sebum
(which is bactericidal).
 linked by tight junctions and
supported by a dense fibrous
basement membrane. Tract
mucus plays a big role in
trapping infiltrating pathogens.
Physical Barriers
The epithelia lining the digestive, respiratory,
reproductive, and urinary tracts 
Respiratory cilia help move the respiratory tract mucus
upwards away from the delicate lung tissue.
The stomach contains a very low pH and proteases
that can destroy pathogens.
Urine flushes the urinary tract while glandular
secretions flush the reproductive tract.
Many secretions contain chemicals and certain
enzymes (such as lysozyme) which damage or kill
bacteria.
Here, we have pathogens traveling down the pharynx
trying to attack the surface cells. How can they be
repelled???
The mucosal cells lining the trachea have released a flood of
mucus, trapping the pathogens! Now what???
The cilia successfully sweep the pathogens up and away!
Phagocytes
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Phagocytes remove cell debris and
respond to foreign invasion. They
are the first line of cellular defense.
Phagocytes include neutrophils,
eosinophils, and macrophages.
Phagocytes remove foreign invaders
primarily via phagocytosis.
The cell can phagocytose and kill
bacteria for minutes to hours before
expiring. Dead phagocytes (primarily
neutrophils) are a major constituent
of pus.
Phagocytes
Immunological Surveillance
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Refers to the constant
monitoring of body cells by
Natural Killer Cells 
recognizing and destroying
any abnormal body cells, e.g.,
tumor cells or cells infected by
a virus.
NK cells destroy abnormal
cells by releasing molecules
called perforins adjacent to the
abnormal cell. These perforins
form a tube that punctures the
abnormal cell membrane and
causes it to lyse.
INTERFERONS
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Small proteins
released by
macrophages,
lymphocytes, and
tissue cells infected
with a virus.
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Note that interferon is
not species-specific.
Complement
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Plasma contains a set
of proteins (made by
the liver) known as
the complement
system.
Inflammation
A localized tissue response to injury that results
in local sensations of pain, redness, swelling,
and heat.
Any stimulus that destroys cells (abrasion,
chemical irritation, pathogen infection,
extreme temperatures) will cause
inflammation. The goals of inflammation are:
 Perform temporary repair and prevent
additional pathogen entry.
 Slow the spread of pathogens away from the
area.
 Mobilize local, regional, and systemic
defenses that can overcome the pathogens
and facilitate permanent repair.
Steps of Inflammation
Fever
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The hypothalamus contains a cluster of
temperature-sensitive neurons that function
in maintaining our stable body temperature.
Bacterial toxins, antigen-antibody
complexes, and interleukin-1 (a chemical
released by active macrophages) all act as
pyrogens.
Pyrogens reset the body's thermostat and
cause a rise in temperature.
The rise in temperature causes an increase
in the body's metabolic rate which allows
the WBCs to function with greater
efficiency.
Also, fever induces the liver and spleen to
sequester zinc and iron - 2 minerals
necessary for bacterial metabolism.
Specific Immunity
Specific resistance is provided by the
coordinated activities of T and B
lymphocytes which respond to
specific antigens.
T cells are responsible for cellmediated immunity - our defense
against abnormal cells and
pathogens living within our cells.
B cells are responsible for humoral
immunity - our defense against
antigens and pathogenic organisms
in body fluids.
Both mechanisms are quite important.
Consider the fact that activated T
cells do not respond to antigens in
solution while antibodies produced by
B cells cannot cross the cell
membrane
There are 3 major types of T
cells:
 Cytotoxic T cells
 Helper T cells
 Suppressor T cells
T Cells
T cells recognize antigens when they
are bound to special proteins in cell
membranes. These membrane
proteins are known as MHC proteins.
Cell mediated Immunity
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T cells that contain the
CD8/4 membrane
protein interact with
MHC proteins.
The binding of another
T cell membrane protein
to a "costimulation
protein”. Once
costimulation has taken
place, the T cell has
been activated.
Activated CD8 cells
undergo a series of
divisions that generate
cytotoxic T cells and
memory TC cells.
Cell mediated
Immunity
Cytotoxic T cells (a.k.a. killer T cells) roam thru injured tissue and when
one encounters its target antigens bound to an MHC protein of another
cell, it will destroy it. This cell destruction is mediated by perforin release
as well as several other chemical weapons
Cell mediated Immunity
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CD4 cells undergo a series of divisions that produce Helper T cells and
memory TH cells. The memory cells remain in reserve while the Helper T
cells secrete a variety of chemicals (cytokines) that:
•Stimulate the cell divisions that produce memory T cells and accelerate the
maturation of Cytotoxic T cells.
•Attract macrophages and stimulate their phagocytic activity.
•Attract and stimulate the activity of NK cells.
•Promote B cell division, plasma cell maturation, and antibody production.
Cell B
proliferation
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It should also be noted that there exist suppressor T cells that act to depress
the actions of both T and B lymphocytes so as to moderate the immune
response and help prevent any self-attack.
Antibody
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shaped like the letter Y.
The base : constant region, the
arms : variable region.
The constant region determines
the class of the antibody
The variable regions contain the
antigen binding sites.
There are 5 classes of antibodies
(immunoglobulins or Igs) in
body fluids: IgM, IgA, IgD,
IgG, and IgE.
Antibodies in each class will
contain the same constant
regions but different variable
regions.
IgM:
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Ig M
First antibody type released during immunization.
Elevated levels indicate recent infection or recent exposure to
antigen.
Extremely good at agglutination b/c it typically exists as a pentamer
(5 monomers hooked together). Each pentamer could potentially bind
10 antigens.
Anti-A and anti-B antibodies are examples.
Activates complement.
IgA:
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Major antibody released in external secretions such as saliva,
mucus, sweat, gastric fluid, and tears.
 Typically exists as a dimer 2 monomers linked together.
 Is of primary importance against local infection in areas such as the
respiratory and gastrointestinal tract.
IgD:
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Expressed on the surface of B lymphocytes where it acts as an antigen
receptor.
IgG:
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The predominant antibody in blood, lymph, and CSF.
Functions include:
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Complement activation.
Toxin neutralization. It is the antibody of choice for passive immunization against
toxins and venoms.
Opsonization.
Immobilization of bacteria.
IgE:
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Its constant region binds with high affinity to basophils and mast cells. Thus,
it can be involved in allergic reactions.
 Also plays a role in protection against parasitic worm infections.
How antibody works
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Neutralization - binding to a toxin or
virus can prevent it from attaching to a
cell and causing damage.
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Agglutination & Precipitation - because
each antibody can bind to at least 2
antigens, antigens bound by antibodies
become linked or clumped together. If
cells are being clumped, this is referred
to as agglutination. If extracellular
molecules are being clumped, it's
referred to as precipitation. In both
cases, the clumped immune complexes
are much more likely to be
phagocytosed.
How antibody works
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Activation of Complement many antibodies contain binding
sites that become exposed
when the antibody binds an
antigen.
Opsonization - antibodies also
act to physically connect
antigens to phagocytes and thus
increase the likelihood of
phagocytosis.
Stimulation of Inflammation - the
binding of antigens to IgE's
embedded in the plasma
membranes of mast cells and
basophils will cause histamine
release.
Autoimmune Disease
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Failure to discern self and non-self.
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Auotimmune diseases can result if lymphocytes are not properly
"educated," those lymphocytes that can attack self-antigens are
not removed in the thymus or bone marrow during development.
They can also occur if new self-antigens appear later in the life.
The immune system can unfortunately see these new antigens
as foreign.
Also, sometimes, bacterial or viral antigens may resemble
proteins normally on the cell surface (e.g., MHC proteins). Thus
the antibodies directed against the bacterial/viral antigen could
then also attack the normal self-protein.
Allergy
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There are 4 types of immune reactions:
 Type I, II, III and IV
The most common food allergic reaction is type I
Contribution of non type I reaction is not clear
Egg, cow’s milk, peanut, soy, wheat, etc
Type I hypersensitivity
 Immediate
hypersensitivity
 Involving Ig E
 Combination of allergen + allergen-specific
Ig E  release of chemical mediators
(histamines, cytokines, prostaglandins,
interleukin, etc) 
 Itching, contraction of smooth muscle,
vasodilation, mucus secretion
Symptoms of food allergies
No System involved
Symptoms
1
Gastrointestinal
Abdominal pain, nausea, vomiting,
diarrhea, GI bleeding, protein losing
enteropathy, oropharyngeal pruritus
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Cutaneus
Urticaria, angioedema, eczema, erythema,
itching, flushing
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Respiratory
Rhinitis, asthma, cough, laryngeal edema,
Heiner’s syndrome, airway tightening
4
Systemic
Anaphylaxis, hypotension, dysrhytmias
5
Unproven
manifestation
Behavioral disorders, tension-fatigue
syndrome, otitis media, neuropsychiatric
disorder, etc
Food intolerance
 Adverse
reactions to food caused by
nonimmunologic or non Ig E mechanism
 Including toxic, pharmacologic, metabolic
or idiosyncratic reactions
 Symptoms includes GI, cutaneus, and
respiratory disorders
 Often similar with food allergy
 Food additives, sulfites, carbohydrates