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Immunity
Immunity
DEFENSE MECHANISMS
I Non specific immunity
General protective mechanisms that kill or prevent the multiplication of
pathogens
Innate or inborn...
Predates adaptive immune response
Found in all multi-cellular organisms
Provides protection against a wide variety of pathogens
Distinguishes self from non-self perfectly
Immune
Surface
Is a two tier defense system Defenses Response
• The skin & mucus membrane
• Inflammation
II Specific immunity
Refers to mechanisms that are activated individually after a Inflammatory Response
microbe or some other foreign material invades an animal body
Acquired...
Not present from birth but acquired during lifetime, developed by the organism in
response to a disease or a vaccine (measles; mumps; smallpox; polio ) 02/11/10
CELLS CHEMICAL BARRIERS
PHYSICAL BARRIERS
granulocytes,
Skin, mucous membrane
monocytes, pH, enzymes
macrophages
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Innate Immunity: Cellular
Components
Granulocytes
Polymorphonuclear leukocytes fight pathogens
(PMN, neutrophils)
inflammation √
Eosinophils allergic and
Basophils (blood) hypersensitivity reactions
Mast Cells (tissues)
fight pathogens
Mononuclear Phagocytes inflammation √
Monocytes (blood) cytotoxicity
Macrophages (tissue) immune regulation
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Neutrophils (PMN) :
Present in blood (60-70% of WBC)
Not normally present in tissues
Short lifespan - 12 hours
Functions:
First cell at the site of infection/injury
Ingest and kill microbes after bactericidal mechanisms activated
(binding to pathogen)
- Produce cytokines/chemokines (initiate inflammation)
Mononuclear Phagocytes:
• Blood - monocytes (1-6% WBC)
• Tissues - macrophages
– Long lifespan – many months
– found in tissues (ex., gastrointestinal tract, skin,)
• Functions:
– Phagocytize and kill after bactericidal mechanisms activated
– Produce cytokines/chemokines (initiate inflammation)
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ACUTE INFLAMMATION
Immediate
Histamine-mediated Temporary (8 - 10 minutes)
fluid release Prolonged (A few days)
Delayed
increased vascular
permeability and
vessel dilatation,
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The sequence of events in the journey of leukocytes from the vessel lumen to
the interstitial tissue, called extravasation, can be divided into the following
steps:
1. In the lumen: margination, rolling, and adhesion to endothelium.. In
inflammation, the endothelium has to be activated to permit it to bind leukocytes, as
a prelude to their exit from the blood vessels.
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Omega 6 Fatty Acid Omega 3 Fatty Acids
(Linoleic Acid) (alpha-linolenic acid)
COX Lipoxygenase
Arachidonic Acid
Prostaglandins Less Inflammatory
PGE1, PGE3 Leukotrienes
(Favorable)
COX Lipoxygenase
Docosahexaenoic acid
(DHA)
Prostaglandins (PGE2)
Inflammatory
Leukotrienes
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CYCLOOXYGENASE PATHWAY
3 important products
Thromboxane A2
–Aggregates platelets and causes vasoconstriction
Prostacyclin (PGI2)
–Endothelial cells inhibits platelet aggregation and causes vasodilation
LIPOXYGENASE PATHWAY
• Leukotrienes
• Leukotriene B4 is a potent chemotactic agent
• Leukotrienes C4, D4, E4
Exogenous
Endotoxins
Endogenous
–Plasma
–Leukocytes
–Endothelial cells
–Fibroblasts
CYTOKINES
Transmitters for cell-to-cell chatting
Modulate cell function
Primarily from activated macrophages and granulocytes
Pro-inflammatory Cytokines
• Tumor necrosis factor-α
• Interleukin-1
• Interleukin-6
• Chemokines ( LTB4; MAP etc )
02/11/10
IL-I and TNF-alpha
“Master Cytokines”
Origin
Monocytes
Macrophages
Similar in action
Endothelium
Acute phase proteins
Fibroblasts
ajor diseases linked to TNF and its family members
Autoimmune Hematopoiesis Protection from Innate Tumor Immune
Deficiency Bacterial inflection Immunity regression surveillance
Syndrome
(AIDS)
Alzheimer’s
disease
TNF
Osteoporosis/
Multiple Bone
sclerosis resorption
Transplant Septic
rejection shock
Diabetes Lymphoproliferative
(type II) diseases
Rheumatoid Pulmonary
arthritis fibrosis
Heart failure
Atherosclerosis
Liver Allergic Fever Tumor Tumorigenesis
disease asthma metastasis
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Aggarwal BB, Nature Rev Immunol. 2003 Sep;3(9):745-56
When a host encounters an injurious agent,
Acute Inflammation…. Turns chronic ? ? ?
phagocytes that reside in all tissues try to get rid of
these agents. At the same time, phagocytes and other
host cells react to the presence of the foreign or
abnormal substance by liberating cytokines, lipid
messengers, and the various other mediators of
inflammation. Some of these mediators act on
endothelial cells in the vicinity and promote the efflux
of plasma and the recruitment of circulating
leukocytes to the site where the offending agent is
located.
As the injurious agent is eliminated and anti-inflammatory
mechanisms become active, the process subsides and the host
returns to a normal state of health. If the injurious agent cannot
be quickly eliminated, the result may be chronic inflammation.
The recruited leukocytes are activated by the injurious agent and
by locally produced mediators.
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Chronic Inflammation
In contrast to acute inflammation, which is manifested
by vascular changes, edema, and predominantly
neutrophilic infiltration, chronic inflammation is
characterized by:
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Differences between Acute and Chronic Inflammation.
Acute Chronic
Fibrosis (collagen – +
deposition)
Operative host responses Plasma factors: complement, immunoglobulins, Immune response, phagocytosis, repair
properdin, etc; neutrophils, nonimmune
phagocytosis
Systemic manifestations Fever, often high Low–grade fever, weight loss, anemia
Changes in peripheral Neutrophil leukocytosis; lymphocytosis (in viral Frequently none; variable leukocyte
blood infections) changes, increased plasma
immunoglobulin
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AUTOIMMUNE DISEASES
02/11/10
SOME AUTOIMMUNE DISEASES
Nervous system:
Multiple sclerosis Myasthenia gravis
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The Parasympathetic
System
The parasympathetic nervous system also
called the craniosacral system contains
ganglia in the midbrain,medull oblongata
and sacrum.
The first two, the cranial ganglia of the
parasympathetic system, give impulses to
the facial, oculomotor, glossopharyngeal,
and vagus nerves.
The sacral group of parasympathetic
nerves originate at the second, third, and
fourth vertebrae and extend nerves to the
bladder, distal colon, rectum, and genitals.
Postganglionic parasympathetic neurons
secrete acetylcholine and are thus
called “cholenergic.”
Blood: Haemolytic anaemia
Thrombocytopenia
Thrombocytopenia
Wegener’s granulomatis
Skin: Psoriasis
Dermatitis herpetiformis
Vitiligo
02/11/10
Ulcerative colitis (IBD)
Gut: Crohn’s disease (IBD)
Grave’s disease
( Hyperthyroidism)
Hashimoto’s thyroidoitis
( hypothyroidism)
Multiple organs:
Rheumatoid arthritis*
Activation
TNF-α IL-2 IL-1 IFN-
Regulation by γ
Cytokines IL-8 TNF-β iNOS IL-6
Inhibition
TGF-β IL-4 IL-10
Mechanisms
of Joint Metalloproteinases PMN’s, Lymphocytes, Immunoglobulin
Destruction: macrophages into joint
02/11/10
Scientific curiosity (study) is
not about winning Nobel Prize
but serving science
Venkatraman Ramakrishnan
Nobel Laureate in Chemistry
2009
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