NK Cells, Macrophages, and Innate Immunity
The Innate Immune System
Specific immunity (humoral or cellular) requires time after antigen exposure, and exhibits memory, but innate immunity occurs without prior exposure
Innate and specific immunities interact with and regulate one another
Components of Specific Immunity: B Cells, T Cells, Fc Receptors, Antibodies
Components of Innate Immunity: Macrophages, Neutrophils (PMNs), Complement, NK (Natural Killer) Cells
Because clonal expansion (i.e. proliferation of specific activated B Cells after exposure to a foreign antigen) is a slow process, our first line of defense is our Innate Immune System.
Acquired and innate immune mechanisms communicate and regulate each other.
Example: Macrophages Þ IL-12 Þ Shift of T cell differentiation from TH2 to TH1.
Innate immune mechanisms are not "specific" in the immunological sense, but they rely on events that are biochemically specific
Example: Receptors bind LPS from a bug in a manner that is biochemically specific, and this may trigger the release of cytokines and start an innate immune response. LPS is not a unique antigen but rather a wall component of all Gram-negative bugs.
Differences Between Innate and Specific Immunity
Depends on antigen-specific, clonally expressed antigen receptors expressed by lymphocytes.
Early in infection. Begins essentially immediately after infection, because we already have the immune components before exposure.
Specific immunity developed in the evolution of vertebrates. Invertebrates rely on innate immunity.
There is no memory involved.
Innate immunity is still important to vertebrates. Specific immunity cannot replace it, partly because specific is too slow.
Disruptions in innate immunity can result in serious immune problems.
Not specific in an immunological sense, but are specific in a biochemical sense.
Contributions to Innate Immunity
Humoral Immunity and Cell-mediated Immunity contribute to both specific and innate immunity
Epithelial Barriers to Infection (first line of defense)
mechanical epithelial cells joined by tight junctions
- specific immunoglobulins
- innate alternative complement pathway
- specific cytotoxic T cells
- innate macrophages and NK cells
chemical fatty acids (skin)
- longitudinal flow of air or fluid across epithelium
- movement of mucus by cilia
Macrophages has a whole medley of receptors on it, each able to bind a gamut of different things, and when it does bind it both secretes cytokines and engulfs and digests the bacteria
- enzymes: lysozyme (saliva, sweat, tears), pepsin (gut)
- low pH (stomach)
- antibacterial peptides: cryptidins (intestine)
- microbiological normal flora compete for nutrients and attachment to epithelium; can produce antibacterial substance
(3) TNF-a activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells and increased fluid drainage to lymph nodes
- Cytokines secreted by a macrophage:
- (1) IL-1 activates vascular endothelium and lymphocytes leading to local tissue destruction, and increases access of effector cells
- Systemic effects: fever, production of IL-6
- (2) IL-8 chemotactic factor for leukocytes (chemotactic means production of a chemical which attracts a cell towards it), increases access of effector cells, activates PMNs (with TNF-
a is secreted in tissues it just has its permeability-inducing affects on local vasculature, when it is secreted into the circulation this affect will devastate the system by causing systemic edema, decreased blood volume, and hypoproteinemia, leading to intravascular coagulation, wasting, and multiple organ failure.
(4) IL-6 lymphocyte activation, increased antibody production
- Systemic effects: Fever, Mobilization of metabolites, Shock
- Note: When TNF-
(5) IL-12 activates NK cells, induces the differentiation of CD4+ T cells into TH1 cells
Interferon (IFN) upon detection of double stranded RNA (i.e. bacterial) there is increased production of IFN-a , IFN-b , TNF-a , and IL-12. This induces NK-cell mediated killing of infected cells, and starts the process of priming T-Cells.
NK cells viruses can interfere with the production of MHC and thus avoid detection. The Immune System uses NK cells to detect this down-regulation of MHC class-1 proteins by the virus. When the NK cell detects this low level of MHC it attacks! This mechanism is normally used as negative-feedback. The MHC (class 1 ONLY) is detected, which signals to NK cells that everything is kosher.
- Systemic effects: Fever, induces acute-phase protein production by telling hepatocytes to make more proteins which help phagocytosis (ex: c-reactive protein, mannnan-binding lectin)
Example of Innate Immunity
A wound penetrating the epithelium allows bugs to get in. Defensins (antibacterial proteins) insert into bugs and start killing them, complement proteins attach to bugs, phagocytes (macrophages and PMNs) rush to the scene, and NK cells start doing their thing
(1) Lymphoctyes Þ "specific" "acquired" or "adaptive" (synonyms), humoral and cellular, requires time to develop after antigen exposure, exhibits memory.
(2) Other cells Þ "innate" immunity, humoral and cellular, expressed even without prior antigen exposure.
(3) The two systems talk to and regulate each other and are combined in a complete immune response.