Transcript The host defense system

From Blood to Host Defense
Host Defense
Gregory J. Bagby, Ph.D.
[email protected]
Office: 310 (CSRB)
From Blood to Host Defense
• Blood
– Components and function
– Hemostasis and clotting
• The host defense system
– General overview
– Innate immune system
• pathogen recognition
• inflammatory response
– Adaptive immune system
• Humoral immune system and antibodies
• Cell-mediated immune system
The Importance of the Host
Defense System?
• Immunology is the study of the host defenses by which
the body (host) protects itself from nonself or altered self.
In the process, it destroys or neutralizes foreign matter,
microorganisms, cells that are infected, and abnormal or
altered self.
• Recognition, Activation and Attack
• Protects against:
– microbial infection – viral, bacterial, yeast, fungi
– non-microbial substances
– “altered” self-cells
• The host defense system has a memory component.
That is, when it sees a foreign molecule it will retain
memory of the encounter so that when it sees it again
it can respond more quickly and robustly.
Where Is the Host Defense
System Located?
• Skin serves as a barrier
• Mucosal surfaces – lung, gastrointestinal track,
genital track – barrier, secretions, epithelial cells,
and specific cells of the immune system
• Liver
• Bone marrow and thymus gland
• Lymphoid tissues – spleen, lymph
nodes, tonsils, lymphatic vessels
• A diffuse system
What Are the Cells of the
Immune System?
• Blood leukocytes – granulocytes, monocytes,
lymphocytes, natural killer cells.
• Tissue-resident cells
– Macrophages & dendritic cells in lung, skin, liver,
barrier tissues
– Lymphocytes in mucosal tissues and lymphoid
tissues
– NK cells lymphoid tissues
– Mast cells in almost all tissues
– All these cells can be found in other tissues
Where Are Cells of the Immune
System Produced?
Cell Category
Granulocytes
Monocytes
Lymphocytes
Location
Bone marrow
Bone marrow
Bone marrow; Mature in
bone marrow (B cells and
NK cells) and thymus (T
cells); Reside and activated
in peripheral tissues and
lymphoid organs
Mast cells
Bone marrow, then reside in
most tissues
How Are Immune Cells Related
to Each Other?
General or Early Name
Differentiated Name
Granulocytes
Neutrophils; Basophils;
Eosinophils
Monocytes
Macrophages, microglial cells,
Kupffer cells, dendritic cells –
antigen presenting cell
T lymphocytes
T helper; Cytotoxic; Regulatory
Naïve; Memory; Effector
B lymphocyte
Naïve; Memory; Plasma cell;
Dendritic cell
NK cell (lymphocyte derived)
Mast cell
NK cell
Mast cell
How Do Cells of the Immune System Communicate
with Each Other and with Other Cells?
• Cell to cell contact via adhesion molecules,
receptors and immunoglobulins.
• Production and secretion of signaling proteins
called cytokines, chemokines and growth
factors, as well as immunoglobulins.
• Production of lipid mediators
• Serve as autocrine, paracrine or hormone
mediators
Cytokines, Chemokines and Growth Factors
• Regulate immune cell proliferation,
differentiation and function.
• Names
– Interleukins 1 to >30
– Interferons (α,β,γ)
– Growth factors (e.g. granulocyte colony-stimulating
factor)
– “Functional” names like tumor necrosis factor,
macrophage inhibitory peptide
– CC, CXC, etc chemokines
• More than a 100 of these.
The Host Defense System Can Be Divided
into Two Categories:
• Innate host defense system (nonspecific)
– Includes barriers such as the skin, and the lining fluid and cells
that line the airways and gastrointestinal track.
– Many cells of the innate system have receptors that bind
(recognize) limited number of foreign molecules.
– Innate cells become activated and have ability to destroy foreign
body.
• Adaptive (Acquired) host defense system (specific)
– Limited number of cells recognize a large array of foreign
molecules or region of molecules called an antigen.
– Cells of adaptive system recognize molecular shapes that are
nonself and proliferate and become activated to mount a
defense leading to destruction of the antigen or a cell infected
by the antigen (nonself).
Innate vs. Acquired Immunity
Activation
Innate recognition on many
cells that are capable of
mounting a defense.
Innate Immunity
Fast
Attack
Recognition
Eradication
(Differences btw/
Inn. Vs. acq.)
of pathogen
Attack
Slow
Activation
Specific recognition by a
few cells that need to
expand before an
effective defense can be
mounted. Adaptive
Adaptive Immunity
Innate Immunity
Cells
Receptors
for detection
of microorganisms
Receptor
repertoire
Monocytes / Macrophages
Polymorphonuclear
Dendritic
PRRs:
Encoded in the germline
Adaptive Immunity
T&B
Lymphocytes
TCRs / BCRs:
Generated randomly by
gene recombination
Limited
Unlimited
Broad
Narrow
Molecular Patterns
shared by classes of microbes
Structural details
(e.g., specific peptides)
Specificity
Reaction
Immediate
3-5 days
Memory
No
Yes
How Do the Innate and Adaptive Limbs
of the Immune System Interact to Defend
the Host from Foreign Invaders?
• Cells of the innate system recognize something as
foreign or abnormal and initiates a host defense
response
– produces cytokines
– kills the invader by producing toxic substances and phagocytosis
– Initiates response of the adaptive system by presenting antigen
• In response to antigen specific cells of the adaptive
system expand in number to recognize, attack and kill
the foreign invader.
• The adaptive system calls upon cells of the innate
system to help in ridding the body of the invader.
What Are the Cells of the Innate and
Adaptive Immune Systems?
Category
Innate immune system
Cells
Monocytes/Macrophages
Granulocytes
Mast cells
NK cells
Dendritic cells
Adaptive immune system
T lymphocytes
T helper cell
Cytotoxic T cell
T regulatory cell
B lymphocytes/Plasma cell
From Blood to Host Defense
• Blood
– Components and function
– Hemostasis and clotting
• The host defense system
– General overview
– Innate immune system
• pathogen recognition
• inflammatory response
– Adaptive immune system
• Humoral immune system and antibodies
• Cell-mediated immune system