ImmunoGlobulins have great mechanical flexibility in the hinge region, which allows:
1 - Formation of physical aggregates (complexes) of Antigen and AntiBody.
2 - Linking of a variety of Antigen shapes, in a variety of linkage configurations.
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The Immune System is a defense mechanism characterized by recognition of Nonself, Specificity, and Memory. It has two basic components: Natural Immunity and Acquired Immunity.
Natural
Immunity is bestowed by substances that are capable of acting directly and immediately on foreign matter (Interferon, Properdin, Basic PolyPeptides).
Acquired
Immunity is a normally dormant component of the Immune System. It can be activated in response to specific stimuli. Passive activation (by the injection of previously activated components) is possible, but the essense of the Immune System is active Acquired Immunity, derived from circulating Lymphocytes.
Immune
Reactions
Fully developed Immune Reactions involve AntiBody
Synthesis by B-Cells (Humoral Response) as well as direct, CytoToxic T-Cell Responses.
B-Cells
B-Cell activation and cloning are under the control of T-Cells:
- Helper T-Cells (CD4+) Promote cloning.
- Suppressor T-Cells Inhibit cloning by blocking Helper T-Cells (CD4+).
T-Cells
T-Cell behavior is determined by the interaction between T-Cell and the HLA-determined GlycoProtein binding sites on the Antigen-Presenting Cell.
Humoral Responses
These begin when a B-Cell recognizes and binds Antigen to its surface binding sites. But, cloning occurs only after the B-Cell and Antigen have received a signal from an Activated Helper T-Cell (CD4+).
The presence of Class II HLA products directs the formation of a Helper T-Cell (CD4+). Formation of activated Helper T-Cells is a two step process:
- Presentation of the Antigen, bound to the surface of a presenting Macrophage in conjunction with Class II HLA products.
- Activation and proliferation of the Helper T-Cell (CD4+). This requires InterLeukin 1, a soluble factor derived from Macrophages.
Activated Helper T-Cells (CD4+) are able to recognize an Antigen bound to the surface of B-Cells in association with Class II HLA products and they are stimulated by this complex to secrete the factor(s) required for B-Cell Proliferation and AntiBody Production.
CytoToxic Responses
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These are initiated when precursors of Killer T-Cells recognize and bind Class I HLA surface markers on a foreign cell.
Subsequent differentiation and proliferation occurs only after a signal from Activated Helper T-Cells. (Their formation is thought to be directed by Class II HLA products.)
Thus, recognition of coexisting Class I incompatibilities (by precursors of Killer T-Cells) and Class II incompatibilities (by Activated Helper T-Cells [CD4+]) on the same cell causes the release of InterLeukin 2 from Activated Helper T-Cells (CD4+).
This leads to the formation and replication of Activated T-Cells that are specific for the Class I HLA surface incompatibility that initated the response. CytoToxic agents, whose precise nature is not yet known, will then destroy the foreign cell.
HLA Surface Glycoproteins
Genes within the HLA complex code for two different types of surface Glycoproteins, named Class I and Class II products.
Class I Products are present on all cells and lead to CytoToxic T-Cell responses in an invading organizm.
Class II
Products
- have more limited distribution;
- are present on B-Cells and
- can be induced by soluble factors derived from Macrophages and from Epithelial Cells;
- cause proliferation of a group of T-Cells (Helper T-Cells [CD4+]) that regulate activation and cloning of B-Cells.
The Micro-Circulation
Structure:
Arterioles & Metarterioles
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These vessels contain Smooth Muscle Units and, therefore, serve as controlling elements. Capillaries often do not directly join Arterioles, but branch from Metarterioles that form preferential flow channels.
Capillaries
Smooth Muscle fibers form the Precapillary Sphincter at the junction between Capillary and Metarteriolle. Beyond that, Capillaries contain only Endothelial Cells with varing sizes and numbers of junctions between them.
Nonfenestrated (Continuous) Capillaries are found in Brain and Muscle, they have few Endothelial junctions, and their Clefs are small.
Fenestrated Capillaries are found in Renal Glomeruli and in the Splanchnic Bed, they have more Endothelial junctions.
Discontinuous Capillaries are found in Liver, Spleen, and Bone Marrow, they have many and large Endothelial junctions.
Venules
Smooth Muscle Units reappear at this end of the MicroVascular unit and permit these vessels to act as elements that control flow. In addition, their permeant structure allows them to participate in the exchange functions of the Micro-Circulation.
Terminal Lymphatics
Lymphatic Microvessels are anchored to surrounding tissue by Microfilaments. They exhibit spontaneous contractile activity. Larger Lymphatic vessels have Valves; this permits unidirectional pumping of Lymph.
Arteriovenous Anastomoses
These muscular bypass channels are found in some tissues - most prominently in those occasionally requiring a Blood Flow far in excess of metabolic needs (ex. the Skin).
Function
Endothelia;
Micromilieu
Capillary Endothelial Cells synthesize many factors. Their functions range from Modulation of Flow (Endothelin) to Modulation of Hemostasis (Prostacyclin, PGI2). This rich area of Cardiovascular Physiology lies beyond the scope of this book.
Substances Exchange Across The Endothelium
Substances move across Capillary Endothelium at rates that are determined by Concentration Gradients, Pressure Gradients, and Endothelial Permeability:
- Lipid Soluble Substances move through Endothelial CytoPlasma; other substances move through Cell Junctions or via Pinocytotic Vesicles.
- Loss of fluid to the Interstitium is an inevitable consequence of the existence of a Hydrostatic Pressure within the Leaky Capillaries. Homeostasis requires that the lost fluid be recaptured.
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Balance Of Fluid Exchange Across Capillary Endothelium Is Maintained By Two Mechanisms:
- A Hydrostatic Pressure Gradient tends to push fluid out of the Capillary, and an Opposing Protein-Osmotic (Oncotic) Pressure Gradient tends to draw Fluid into the Capillary.
- Excess Interstitial Fluid is removed by Lymphatic Uptake.
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A Microcirculatory unit consists of an Arteriole, perhaps a small number of Metarterioles, several Capillaries, a Venule, perhaps an Arteriovenous Anastomosis (A-V Shunt), and several Terminal Lymphatics.
- The Tone of Precapillary Sphincters determines the fraction of Regional Flow that passes through True Capillaries.
- The Tone of Smooth Muscles in Arteriole, Metarteriole, and Venule determines Total Flow through the Microvascular Unit.
- The Tone of Precapillary (Arteriolar and Metarteriolar) Smooth Muscle relative to Postcapillary (Venular) Smooth Muscle determines the Hydrostatic Pressure wihin Capillaries.
Fluid Exchange Across The Endothelium
- The Rate of Fluid Loss is governed by Transmural Gradients in Hydrostatic and Oncotic pressures.
- When there is Flow in a Capillary, Fluid leaves along most of the Length of the Capillary.
When there is No Flow in a Capillary, Fluid enters along the Whole Length of the Capillary.
Periodic Closure of Capillaries (Vasomotion) ensures a balance between Capillary Fluid Loss and Fluid Gain. |