from blood to host defense host defense gregory j. bagby, ph.d. gbagby@lsuhsc.edu office: 310 (csrb)
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From Blood to Host Defense Host Defense
Gregory J. Bagby, Ph.D.gbagby@lsuhsc.eduOffice: 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 Location
Granulocytes Bone marrow
Monocytes Bone marrow
Lymphocytes 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; RegulatoryNaïve; Memory; Effector
B lymphocyte Naïve; Memory; Plasma cell; Dendritic cell
NK cell (lymphocyte derived)Mast cell
NK cellMast 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
Recognition(Differences btw/Inn. Vs. acq.)
Innate recognition on manycells that are capable of mounting a defense.
Specific recognition by a few cells that need to expand before an effective defense can be mounted.
Eradicationof pathogen
Innate Immunity
Adaptive Immunity
Fast
Slow
Activation
Activation
Attack
Attack
Innate
Adaptive
Innate Immunity Adaptive Immunity
Receptorsfor detection
of microorganisms
PRRs:
Encoded in the germline
TCRs / BCRs:Generated randomly by
gene recombination
Receptorrepertoire
Limited Unlimited
Cells
Monocytes / MacrophagesPolymorphonuclear
Dendritic
T & BLymphocytes
Specificity Molecular Patterns
shared by classes of microbes
Broad
Structural details (e.g., specific peptides)
Narrow
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 Cells
Innate immune system Monocytes/MacrophagesGranulocytesMast cellsNK cellsDendritic cells
Adaptive immune system T lymphocytes T helper cell Cytotoxic T cell T regulatory cellB 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
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