Download Nonspecific host defence factors.med.10 ppt

Tvorko M. S.
Host defenses are composed of two
complementary, frequently interacting
systems:
(1)innate (nonspecific) defenses, which
protect against microorganisms in
general, and
(2) acquired (specific) immunity, which
protects
against
a
particular
microorganism.
TWO TYPES OF IMMUNITY
Nonspecific (innate)
•Physical and chemical
agents
•Lysozyme
•Acute phase proteins
•Complement system
•Cytokines (chemokines)
•Phagocytes (granulocytes,
macrophages)
•Natural killer (NK) cells
•Dendritic cells
•Toll-like receptors
Present at birth
Immediate protection against variety of
pathogens and foreign substances
Specific (adaptive)
•Antibodies
(B lymphocytes)
•T lymphocytes
Immunity signifies all those properties of the
host that confer resistance to a specific
infectious agent.
Immunity
Natural
adaptive
(Innate, nonspecific)
Acquired or
(specific)
Passive
Active
Acquired ( Adaptive) Immunity
Active
Natural
Passive
Artificial
Natural
Artificial
(Infection)
(Immunizing agents)
Clinical
Subclinical
(Placental transfer,
colostrum)
(administration of immune sera)
First Line of Defense
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Epidermis
Mucous membranes
 Mucous
 Cilia
 Lacrimal apparatus of
eyes
 Saliva
 Urine flow
 Vaginal secretions
 Defecation and vomiting
Sebum
Perspiration
Lysozyme
Gastric juice
Innate (nonspecific) defenses
Skin and Mucous Membranes
Intact skin is the
first line of defense
against
many
organisms. In addition
to the physical barrier
presented by skin, the
fatty acids secreted
by sebaceous glands
in the skin have
antibacterial
and
antifungal activity.
Mucous membranes

protective covering in intestine, lungs, eyes
etc., that resists penetration and traps many
microbes

antimicrobial secretions

Lysozyme
Lactoferrin: macrophages and PMNs, sequesters
iron
Lactoperoxidase: produces superoxide radicals

mucosal-associated lymphoid tissue (MALT)
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MUCOSAL
SURFACES
•Gastrointestinal
tract
•Respiratory tract
•Urinary tract
•Reproductive tract
Respiratory System
-
The mucociliary blanket of the respiratory
epithelium traps microorganisms less than 10㎛
diameter
- The bronchial-Associated Lymphoid Tissue (BALT)
Gastrointestinal Tract
- In the stomach : lower pH, enzymes
⇒ destory
- In the intestine : enzymes
microorganisms
- In the large intestine : the normal microbiota
⇒ preventing the
establishment of
pahtogens
A second
important defense
is the mucous
membrane of the
respiratory tract,
which is lined with
cilia and covered
with mucus. The
coordinated
beating of the
cilia drives the
mucus up to the
nose and mouth,
where the
trapped bacteria
can be expelled.
Genitourinary Tract
- Urine kills some bacteria due to its low pH
and the presence of urea and other
metabolic end products
The Eye
- Tears contain large amount of lysozyme,
lactoferrin and sIgA
In lacrimal fluid, sputum,
saliva,
blood,
milk,
tissues
and
organs
lysozyme is found. It is
found in some bacterial
cells.
Nasal
mucus
is
bactericidal for many
microbes and viruses of
influenza,
herpes,
poliomyelitis, etc.
Second Line of Defense

1.
Antimicrobial proteins
Interferons (IFNs)

2.
Complement system
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3.
Antivirals that prevent replication of virus
Enhance immune reactions
Transferrins

Inhibit bacterial growth by reducing available
iron
Interferons (IFNs)

Interferons (IFNs) are antiviral proteins produced in
response to viral infection.
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alpha-IFN,
beta-IFN,
gamma-IFN.
The mode of action of -IFN and -IFN is to induce
uninfected cells to produce antiviral proteins
(AVPs) that prevent viral replication.
Interferons are host-cell–specific but not virus-specific.
Gamma-interferon activates neutrophils and
macrophages to kill bacteria.
Complement
Complement, or the complement system, refers to a
set of more than 20 large regulatory proteins produced by
the liver that circulate in plasma in an inactive form.
They account for about 10 percent (by weight) of all
plasma proteins.
The general functions of the complement system are to
enhance phagocytosis, produce inflammation, and
directly lyse microorganisms. These functions are
nonspecific: When the complement system is activated,
complement proteins participate in a cascade of reactions
that trigger an inflammatory response.
IgA and IgE cannot activate complement
Late Steps of Complement Activation
Cytolysis Caused by Membrane Attack Complex
Complement-Mediated Lysis of E. coli
Alive
Killed
The general functions of the complement system
Transferrins
Transferrins are iron-binding
proteins. Inhibit bacterial
growth by reducing the
amounts of available iron.
Lactoferrin is present in
tears, semen, breast milk,
bile, and nasopharyngeal,
bronchial, cervical, and
intestinal
mucosal
secretions. Transferrin is
present in serum and the
intercellular spaces of
many tissues and organs.
Transferrin transports iron from the small
intestine, where the iron is absorbed, to
the tissues, where the iron is used.
Transferrin and lactoferrin bind iron,
limiting the growth of pathogens in the
blood.
Second Line of Defense
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Natural killer (NK) cells
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Phagocytes
Phagocytosis
Neutrophils
Macrophages
 Develop from monocytes
 Wandering
 Fixed
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~ 5 – 10% of lymphocytes
In spleen, lymph nodes and red bone marrow
Attack body cells displaying abnormal plasma membrane
proteins
Perforin perforates cell membranes
Granzymes destroy cell proteins
Phagocytosis
Phagocytes recognize
the enemy either
Directly, by binding to
components on the
surface of the
organism or
Indirectly, by binding
to a foreign entity
that has antibody
bound to it.
Figure 21.8a
Phagocytosis
Killing mechanisms of phagocytes
SEM of macrophage engulfing E. coli cells on the
surface of a blood vessel
Macrophage Attacking E.coli
(SEM x8,800)
Alveolar (Lung)
Macrophage Attacking
E. coli (SEM x10,000)
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Natural Killer Cells Recognize and Kill Abnormal
Cells
 NK cells are formed in the bone marrow, and
migrate to:
 tonsils
 lymph nodes
 spleen
 When activated, they produce cytokines that
trigger response by macrophages and other cells
 Then they move into blood and lymph where they
kill:
 cancer cells
 virus-infected cells
Natural Killer Cell Function
Figure 22–11
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When an NK cell recognizes a cell as “non-self” it
releases cytotoxic perforins and granzymes
ADCC by NK Cells
Destruction of Virus-Infected Cells by NK Cells through
Antibody-Dependent Cellular Cytotoxicity
(ADCC)
The inflammatory response mobilizes nonspecific
defense forces
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Tissue damage triggers the inflammatory response
The inflammatory response can
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Red, swell, warm
disinfect tissues
limit further infection
Non-specific defense system
Skin surface
Swelling
Pin
Phagocytes
Bacteria
Chemical
signals
White
blood cell
1 Tissue injury; release of
chemical signals such as
histamine
Phagocytes and
fluid move
into area
2 Dilation and increased leakiness3 Phagocytes (macrophages and
of local blood vessels; migration neutrophils) consume bacteria
of phagocytes to the area
and cell debris; tissue heals
Innate Immunity Depends on ReceptorRecognition of Common Pathogen-Associated
Molecules
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Pathogen-associated molecular patterns (PAMPs)
help the innate immune system recognize
pathogens
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Toll-like receptors (TLRs) are signaling receptors
on:
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macrophages
dendritic cells
endothelial cells
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TLRs mediate a specific
response to distinct
PAMPs
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They stimulate the
secretion of cytokines,
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For example, those that
stimulate production of
acute phase proteins
The TLR response must
be regulated to prevent
infection and immune
disorders
Cytokines
•“Cytokines” are soluble protein mediators
secreted by immune cells (mostly) that act on
other cells to regulate their activity; many are
called “interleukins” (IL-1, IL-2, etc.)
•Cytokines have many functions, we’ll focus on a
few central functions of a few key cytokines
•A subfamily of cytokines primarily functions in
directing migration of cells, these are called
“chemotactic cytokines” or “chemokines”
- monokines,
lymphokines,
interleukines
colony stimulating
factors, chemokines,
interferon
- The four cytokine
families
Function :
• autocrine
• paracrine
• endocrine
Cytokine receptor families
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A summary of innate and acquired immunity
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Skin
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal defenses
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Break !