Transcript Introduction and Innate Immunity

Overview on Immunology and
Introduction to Innate
Immunity
Over view
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What are the main types of white
blood cells?
Name the two main types of immunity?
What are the main distinctions between
these two categories?
What cells are involved in which aspects
of the immune system?
Lymphocytes
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Many types; important in
both humoral and cellmediated immunity
B-cells produce
antibodies (APC cell)
T- cells
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Cytotoxic T cells
Helper T cells
Memory cells
Lymphocytes
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Natural Killer cells
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Large granular lymphocytes (not B or T)
Kills tumor cells
Kills cells infected with certain viruses
(intracellular pathogens)
Monocytes/Macrophage
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Phagocytosis and killing of
microorganisms
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Activation of T cells and
initiation of immune
response
Monocyte is a young
macrophage in blood
There are tissue-specific
macrophages
APC cells
Dendritic Cells
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Phagocytosis and killing
of microorganisms
Function as antigen
presenting cells (APC)
In the blood and
tissues – mature and
migrate to the lymph
nodes
Neutrophil
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Granulocyte
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Cytoplasmic granules
Polymorphonuclear
Phagocytosis
Short life span (hours)
Very important at “clearing” bacterial
infections
Innate Immunity
Eosinophils
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Kills Ab-coated parasites
through degranulation
Involved in allergic
inflammation
A granulocyte
Double Lobed nucleus
Orange granules contain toxic
compounds
Basophils
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Might be “blood Mast
cells’
A cell-killing cells
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Blue granules contain toxic
and inflammatory
compounds
Important in allergic
reactions
Antigen-presenting cells (APC)
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Highly specialized
Process antigen and display peptide
fragments on cell surface
Involved in T-cell activation
Macrophages, dendritic cells and B-cells
Over view
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What are the main types of white blood
cells?
Name the two main types of
immunity?
What are the main distinctions
between these two categories?
What cells are involved in which aspects
of the immune system?
Immune system divisions
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Innate immunity
 First line of defense
Adaptive (acquired) immunity
 Takes time to develop
 Humoral immunity
(antibody–mediated
specific immunity)
 Cell-mediated immunity
(The aspect of the
adaptive immune response
where antigen-specific T
cell have a main role)
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Active immunity
Passive or maternal
immunity
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Injection of Immunoglobulin
Absorption of maternal
antibodies
Innate vs. adaptive immunity
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Innate immunity
 First line of defense (present in all individuals at all
times)
 Immediate (0 – 4 hours)
 Non-specific
 Does not generate lasting protective immunity
Adaptive immune response (late: > 96 hours)
 Is initiated if innate immune response is not adequate
(> 4 days)
 Antigen-specific immunity
 Generates lasting protective immunity (e.g. Antibodies,
memory T-cells)
Over view
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
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
What are the main types of white blood
cells?
Name the two main types of immunity?
What are the main distinctions between
these two categories?
What white blood cells are
involved in which aspects of the
immune system?
Immune system cells
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Innate immunity
 Granulocytes
(i.e. neutrophils)
 Macrophages
 Dendritic cells
 Natural killer (NK)
cells
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Adaptive
immunity
 Lymphocyte
B cells
 T cells
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Cytotoxic T cells (CTLs)
Helper T cells (Th)
Memory cells
Innate immune system
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The first line of defense:
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Penetration of the epithelial surface of the body by
microorganism (e.g. bacteria)
Engulfment of microorganism by macrophages,
neutrophils, and dendritic cells
Release of cytokines and chemokines
Inflammation
(Immunology animation: Janeway)
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http://www.blink.biz/immunoanimations/#
Killing by granulocytes
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Macrophages and neutrophils recognize pathogen by means of
cell-surface receptors
 Example: mannose receptor, CD14 receptor, scavenger
receptors, glucan receptor etc.
Binding of MØ/neutrophils with pathogen leads to phagocytosis
 Bound pathogen is surrounded by phagocyte membrane
 Internalized (phagosome)
 Killing of pathogen (Phagolysosome*)
 Oxidative burst (synthesis of hydrogen peroxide (H2O2)or
free oxygen radicals)
 Acidification
 Antimicrobial peptides (e.g. defensins)
* Phagolysosome = lysosome +phagosome
Phagocytosis
Lipid
mediators
Mannose
receptor
Lysosome
Phagosome
Scavenger
receptor
LPS receptor
(CD14)
The macrophage
expresses receptors for
many bacterial
constituents
Cytokines
Bacteria binding to
macrophage receptors
initiate the release of
cytokines and small lipid
mediators of inflammation
Phagolysosome
Macrophages engulf and
digest bacteria to which
they bind
Phagocytosis
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(Immunology animation: Janeway)
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http://www.blink.biz/immunoanimations/#
Immune response (IV)
9.1 - Phagocytosis
Humoral immune response
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Cell-surface immunoglobulin
receptors (BCR) detect
extracellular pathogens
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Once activated, secrete
immunoglobulins as soluble
antibodies
Antibodies
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Variable region (2 identical
antigen-binding sites)
Constant region (determines
how antibody disposes of the
pathogen once it is bound)
V region; At binding
Fc region
Cell killing – NK cells
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NK cells do not require prior
immunization or activation
They attach to ‘target’ cells
(ADCC)
Cytotoxic granules are
released onto surface of cell
Effector proteins penetrate
cell membrane and induce
programmed cell death
Inflammation
Inflammatory cells
migrate into tissue,
releasing inflammatory
mediators that cause
pain
Chemokines
Cytokines
Bacteria
trigger
macrophages
to release
cytokines and
chemokines
Proteins
Fluids
Vasodilation and
increased vascular
premeability cause
redness, heat, and
swelling
Cytokines
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Low molecular weight, soluble proteins that are
produced in response to an antigen and function as
chemical messengers for regulating the innate and
adaptive immune system
Innate immune system
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Macrophages and Dendritic cells
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Tumor necrosis factor-alpha (TNF-)
Interleukin-1 (IL-1)
Interleukin-12 (IL-12)
Adaptive immune system
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T-lymphocytes
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Interleukin-2 (IL-2)
Interleukin-4 (IL-4)