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What is the Immune System:
A collection of molecules, cells, tissues and organs whose primary funciton is defense
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Exceptions to the Primary Defensive Role:
- Exaggerated specific responses to non-pathogenic environmental antigens (allergy)
- Any exaggerated specific responses that are tissue damaging (hypersensitivities)
- Specific, exaggerated and destructive responses to self-antigens (autoimmunities)
- Variable responses to self, neoantigens - (cancers)
- Strong barriers to organ and tissue transplantation (allogenic responses)
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Bodies Barriers:
All surfaces exposed to the "outside world" provide barriers to penetration and infection
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Infection and Inflammation: Sequence of Events in a nonspecific Local Inflammatory Response to Bacteria (6 steps)
- 1. Entry of bacteria into tissue; injury to tissues causes release of chemicals to initiate the following events
- 2. Vasodilation of the microcirculation in the infected area, leading to increased blood flow
- 3. Large increase in protein permeability of the capillaries and venules in the infected area, with resulting diffusion of protein and filtration of fluid into the interstitial fluid
- 4. Chemotaxis: movement of leukocytes from the venules into the interstitial fluid of the infected area
- 5. Destruction of bacteria in the tissue either through phagocytosis or by other mechanisms
- 6. Tissue repair
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Inflammation: General Properties:
Initiators and purpose
- - The body's defense mechanisms in response to tissue damage and/or infection
- Initiators - infection, trauma (physical or chemical), and pathologic immune responses
- Purpose - identify the area affected and call into play mechanisms that lead to: elimation of the inflammatory stimulus and healing
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Two Defense Against Infection
- 1. Innate, non-specific defenses
- 2. Acquired, adaptive, specific defenses
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Innate, non-specific defenses:
- -Physical and/or chemical barriers; i.e. epithelia
- -Molecular - complement, cytokines, chemokines, acute phase proteins
- -Cellular - phagocytic cells, natural killer (NK) cells
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Acquired, adaptive, specific defenses
- -Molecular - antibodies
- -Cellular - lymphocytes: naive, effector, and memory lymphocytes
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The Response by both innate and specific defense systems to Infection consist of 2 Phases:
- 1. Recognition - of a potential pathogen and/or its products by host cells and molecules
- 2. Recruitment and/or generation of destructive effector mechanisms - to contain or eliminate the potential pathogen and/or its products
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The First Time an Individual Encouters a Pathogen (4)
- Immediate - Innate - Physical and chemical barriers
- 0-4 hours - Innate - Molecular and cellular recognition and response
- 4-96 hours - Innate - molecular and cellular recruitment of cells from circulation and their activation
- 4-14 days - Acquired, specific - dendritic cells, macrophage and lymphocytes
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Neutrophils
- The classic phagocytic cell
- (50-70% of all blood leukocytes)
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Monocytes
The precursors to all tissue macrophage (1-6% of all blood luekocytes)
- Released from bone marrow and circulate in blood.
- When they leave blood and migrate into different tissues, the differentiate into macrophage (highly phagocytic cells) characteristic of that tissue
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Macrophage
- The tissue - specific, fully differentiated, highly phagocytic descendents of blood monocytes.
- When partly activated, these cells can also be antigen-processing and presenting cells
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Dendritic Cells
Antigen processing and presenting cells
<<1% of all blood leukocytes
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Most Important Cells Involved in Innate Immune Recognition: (3)
- Dendritic Cells - are capable of recgonizing and responding to smaller pathogens and their molecular products, ex viruses
- Neutrophils and macrophage - capable of recognizing and responding to larger pathogens and pathogenic materials, for example, intact bacteria.
- Natural Killer (NK) Cells = capable of recognizing and responding to virally-infected host cells by killing them.
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Characteristics of Innate Immune Defense Recognition:
- -A limited number of binding specificities (distinct receptors) are expressed by cells of the innate defense system
- -Recognition and response are rapid - measured in minutes to hours
- -There is no specific memory generated as a consequence of recognition and response
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The Major Functions of Cell-Surface Pattern Recognition Receptors
- -Direct uptake of pathogens by phagocytes and dendritic cells.
- - Macrophage mannose receptors
- - Macrophage scavenger receptors
- -Triggering signaling pathways (example: toll-like receptor (TLR) signaling) stimulates production of anti-microbial peptides and inflammatory cytokines
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Innate Cellular Immunity to Infection
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Tissue macrophage (and dendritic cells) are the sentinel cells
- –Macrophage attempt to phagocytose and kill the microbe intracellularly
- –Macrophage secrete cytokines and chemokines in response
- –The endothelial cells of blood vessels adjacent to the site are “activated”
- –Inflammatory cells, like neutrophils, are recruited to the site
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Innate Cellular Effector Mechanisms
- •Phagocytic cells like neutrophils, which have been attracted to sites of inflammation and both resident tissue macrophage and additional recruited monocytes/macrophage are capable of very fast action
- •Phagocytic activity may often be sufficient to clear the pathogen
- •If the infection is not completely cleared, these cells can contain the infection until the specific defenses can be mobilized
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