# data[].attributes.body
- Immunity protects animal against microbial invasion and is essential for life (ensure health and survival
- Includes physical barrier, innate and adaptive immunity

# data[].attributes.body
- Provide rapid (immediate response) initial protection
-Non specific
Involves physical barriers like skin

# data[].attributes.body
- Provide prolonged effective immunity
- Highly specific (Antigen specific)
- Directed against bacterial invaders; mediated by antibodies (Ab), binds to bacteria mark for destruction
- Includes both humoral and cell mediated immunity components
- Effectiveness improves with exposure
- A memory of an encounter is reatined

# data[].attributes.body
= Dendritic cells are presence in site of infection and take up the pathogen as innate immunity fails to control the infection, then will differentiate and mobilised to 2ndary lymphoid tissue  and activate adaptive immune respone.
= Macrophage engulf, express MHCII and recognized by helper T-cell

# data[].attributes.body
1. Dendritic cell or DCs (phagocyte, multi-functional)
- Found in tissues, lymph nodes, skin, mucosal surfaces etc.
- the ONLY cells capable of activating naive T cells (Clark & Kupper, 2005)
- Macrophage produce CHEMOKINES>> Attract DCs (immature) to site of infection>> sample tissue environment>> detect pathogen through TLRs>> @recognition = Matures>> Present Ag>> Activates cells of Adaptive immune system (activate T cells>> Signal B cells>> Ab production (Antigen specific)
- Once pathogen has been removed, adaptive response ensure host is protected from a repeated attack by the same pathogen

2. Mast cells
- found at surfaces exposed to microbes (Skin/ mucous membrane)
- Granulated (with histamine, lipid mediators, cytokines, chemokines)
- Express TLRs
- Can direct immune cells to infection site >> modulate DCs activation// Ag presentation//  Expression of costimulatory molecules >> influence adaptive response

3. Basophils

- found in blood
- Granulated (with vasoactive molecules, +- mast cells), involved in more chronic inflammation
- Pdt of IL-4 >> Th2 differentiation >> Acquired immune response

# data[].attributes.attachment_link.title
Interaction between innate and adaptive immunity

# data[].attributes.attachment_link.description
The interaction between innate and adaptive immunity is mediated by a type of phagocyte called a dendritic cell. These cells are multifunctional; they can detect pathogens and activate an innate response, eliminate pathogens through phagocytosis and, uniquely, activate T cells which in turn signal B cells, leading to the production of antigen-specific antibodies.

# data[].attributes.body
- In innate immune response, PRRs (Pattern Recognition Receptors) is important in recognizing conserved PAMPs (Pathogen Associated Molecular Patterns)
- PRRs:

Primarily expressed by APM (Antigen Presenting Macrophage/ DCs)

Localised on the cell surface (detect extracellular pathogens) // within endosomes and cellular matrix (detect intracellular invading viruses)

Key role in activating pro-inflammatory signalling pathways, stimulating phagocytic responses, binding to microbes as secreted proteins

- PAMPs are

unique to each pathogen

Essential molecular structures required for pathogen survival

# data[].attributes.body
First successfully  transplanted organ is the cornea.
-no administration of immunosuppressive drugs
-no assessment of HLA type

# data[].attributes.body
The first successfully transplanted organ is the cornes, and the reasons are :
-no immunosuppression drugs
-no HLA assessment

# data[].attributes.body
Overview of Innate immunity
Taken from Veterinary Immunology, 9th edition, by Ian Tizard

# data[].attributes.body
Signals trigger innate immunity

# data[].attributes.body
An immune response pertains to any of the body's response to a foreign substance, such as an antigen. The response intends to protect the body from antigens, e.g. disease-causing viruses, fungi, and bacteria. A transplanted organ may also incite an immune response when it is identified as not-self.

# data[].attributes.body
A SUMMARY OF INNATE AND ADAPTIVE IMMUNITY

# data[].attributes.body
ALERT: I think these points can be describe as examples. Yet, these are very difficult to understand. (PhD level)
Information from a Journal, see link below.

- Cross-talk between the innate and adaptive systems may be bidirectional. The major cytokines implicated in atherosclerosis are produced by cells of both the adaptive and innate immune systems, acting upon one another in both a paracrine and an autocrine manner.

- For instance, IFNγ produced by the effector T-helper 1 (Th1) cell activates phagocytes such as macrophages, and interleukin-4 (IL-4) and IL-5 produced by Th2 cells, may stimulate some macrophage and dendritic cell subsets.

- IL-5 in particular mediates a link between adaptive and natural immunity.

- On the other hand, IL-12, IL-18, and type I interferons promote the differentiation of Th1 cells, and IL-12 can stimulate the production of IFNγ by NK cells.

- IL-10, which can be produced by T-cells, dendritic cells, and macrophages, inhibits IL-12 production and Th1-mediated inflammation.

# data[].attributes.attachment_link.readable_text
Department of Pathology and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637

1To whom correspondence should be addressed. e-mail: getz{at}bsd.uchicago.edu

So far in this series of thematic reviews, we have dealt with aspects of the innate immune system in relation to atherosclerosis. Forthcoming reviews will focus more on aspects of the adaptive immune system or in some cases on the way the two systems, innate and adaptive immunity, may "talk" to one another.

In innate immunity, signaling is through germ-line receptors of limited repertoires that respond by pattern recognition of exogenous agents and antigens. The promptness of the response is a consequence of the availability of innate or natural immune cells that express their responding receptors before exposure to the stimulants. These receptors include the scavenger receptors discussed in this series by Greaves and Gordon ( 1) and the Toll-like receptors (TLRs) reviewed by Tobias and Curtiss ( 2). These receptors are primarily present on monocytes/macrophages and dendritic cells, which may be activated as antigen-presenting cells. They may also be present on natural killer (NK) cells, endothelial cells, and cells of the adaptive immune system. On the other hand, the adaptive immune system is composed of cells bearing rearranged cell surface receptors, generating an almost unlimited diversity of recognition response elements.

Bridging these two branches of the immune response are a number of cell types that have functional characteristics of both systems. Among these cells are the B1 cells, the γδ T-cells, and perhaps natural killer T (NKT) cells. These cells express immunoglobulins or T-cell receptors that have much more limited diversity than traditional B- and T-cells of the adaptive immune system. The majority of B1 cells produce natural IgM antibodies that recognize altered self molecules such as oxidized LDL. These cells are present at birth, having been selected during ontogeny, perhaps in response to apoptotic cells. This characteristic allows them to respond promptly like an innate immune cell, for example to a mimic molecule such as the phosphatidylcholine of Streptococcus pneumoniae ( 3). B1 cells and the natural antibodies that they secrete will be discussed in detail in a forthcoming review by Binder and colleagues. γδ T-cells and NKT cells also recognize antigens of limited diversity. The former does so in some cases without the necessary involvement of major histocompatibility complex (MHC) molecules, whereas the invariant T cell receptor on NKT cells recognizes lipid antigens in the context of CD1, a MHC class I-related protein. Recent work has implicated these cells in atherosclerosis, which will be discussed in more detail in a forthcoming review by VanderLaan and Reardon.

The immune system as a whole represents a very complex interacting network that includes within it proinflammatory and anti-inflammatory mediators. The communication between the innate and adaptive immune systems involves cell-cell interactions in relation to antigen presentation or soluble molecules such as cytokines or chemokines. These are not necessarily mutually exclusive interactions. The response to presented antigens is often a major basis for the stimulation of adaptive immune cells to produce cytokines. These interactions can result in either target cell activation or suppression. Such networks of communication are likely at play between innate and adaptive immune systems or between components within each of these systems themselves. For example, NK cells can lyse immature dendritic cells as well as positively regulate dendritic cell maturation ( 4, 5).

Furthermore, cross-talk between the innate and adaptive systems may be bidirectional. The major cytokines implicated in atherosclerosis are produced by cells of both the adaptive and innate immune systems, acting upon one another in both a paracrine and an autocrine manner. For instance, IFNγ produced by the effector T-helper 1 (Th1) cell activates phagocytes such as macrophages, and interleukin-4 (IL-4) and IL-5 produced by Th2 cells may stimulate some macrophage and dendritic cell subsets, as discussed below. IL-5 in particular mediates a link between adaptive and natural immunity ( 6), and this will be discussed in detail in a forthcoming review by Binder et al. On the other hand, IL-12, IL-18, and type I interferons promote the differentiation of Th1 cells ( 7), and IL-12 can stimulate the production of IFNγ by NK cells ( 8). IL-10, which can be produced by T-cells, dendritic cells, and macrophages, inhibits IL-12 production and Th1-mediated inflammation. The effects of cytokines on various target cells will be addressed in more detail in two forthcoming reviews in this series. Elaine Raines will discuss the smooth muscle and endothelial cell targets, and Alan Daugherty will focus on monocytes and other leukocytes.

Much of the communication between the innate immune system and its adaptive immune partner relies on the presentation of an antigen. Yet, the adaptive immune system is not required for the development of pronounced atherosclerosis ( 9). This places heavy emphasis on the role of the innate system in atherosclerosis.

The innate immune system is generally thought to yield prompt, blunt responses to stimuli. However, the innate immune response may not be as blunt as once supposed, and within each major class of innate cells there is considerable specificity and heterogeneity. Heterogeneity among innate immune cells is worthy of further consideration.

Because monocyte recruitment is central to the pathogenesis of this disease, the innate immune system is at the core of atherogenesis. Not widely recognized is the difference between the resident macrophage, of which the Kupffer cell is an example, and the inflammatory macrophage, which is presumably the macrophage subtype involved in atherosclerosis ( 10). Gordon ( 10) has defined five sets of activation/deactivation signals that influence macrophage phenotype. Activation of macrophages in response to microbial stimuli, mediated by unique microbial plasma membrane molecules through TLRs or scavenger receptors, results in the production of type I interferons and the upregulation of costimulatory molecules. Although microbial infection may modulate atherogenesis, it is most likely that endogenous altered self ligands such as oxidized LDL play a more significant role in atherosclerosis. As outlined by Tobias and Curtiss ( 2) in their review in this series, at least two TLRs have been implicated in atherosclerosis, TLR4 and TLR2. Engagement of the TLR facilitates the antigen-presenting capability of the innately activated macrophages. Of interest is the recent observation that TLR2 is regulated by hemodynamic forces ( 11). A second class of activating molecules influencing the macrophage response are complement and antibodies (via Fc receptors), which also result in the secretion of a variety of cytokine mediators of inflammation. IFNγ is a major activator of the third class of macrophages that is especially relevant to atherosclerosis. This activation results in MHC class II upregulation and the secretion of IL-6, tumor necrosis factor-α (TNF-α), and IL-1, which mediate the acute phase response. MHC class II upregulation may also occur when IL-4 or IL-13 activates macrophages. In this case, this is accompanied by an increased capacity for tissue repair, including collagen production. Finally, macrophages that express large numbers of scavenger receptors and become cholesteryl ester-loaded foam cells, and hence are highly involved in atherosclerosis, may no longer function as effective antigen-presenting cells. However, these cells exhibit increased secretion of anti-inflammatory cytokines, such as transforming growth factor-β (TGF-β) and IL-10, which in turn will enhance this macrophage phenotype by autocrine stimulation.

Each of these macrophage subsets can also be distinguished on the basis of its chemokine secretory profile ( 12). Whether these are separate macrophage lineages or represent a continuum of plastic cell lines is not clear. This differential activation and polarization of the macrophage would be of interest not only with respect to early lesion development but also with respect to the evolution of the macrophage phenotype as the lesion progresses. For example, it has been suggested that the Th2 cytokines IL-4 and IL-13 and chemokines are more abundant in late atherosclerotic lesions ( 13). Such a cytokine profile may induce a macrophage that improves the stability of the plaque, although this interaction remains to be clearly demonstrated experimentally. Similarly, the highly loaded macrophage foam cell may also play a role in immunosuppression in the lesion by its secretion of the anti-inflammatory cytokines IL-10 and TGF-β. Given the important role of the macrophage in lesion formation, the possibility that its phenotype may evolve during lesion progression and thus have different roles at different stages of the lesion is an important area of future atherosclerosis research.

In recent years, a new understanding has developed of the relationship between lipid metabolism in the artery wall, especially in macrophages, and inflammation. Oxidized LDL is regarded as a major neoantigen in atherogenesis and is probably the major source of the lipids that are stored in the macrophage foam cells. Although the bulk of the lipid stored in foam cells is cholesteryl ester, it is likely that increased concentrations of lipid signaling molecules, such as unsaturated fatty acid and oxysterol, are also present. These serve as ligands for the peroxisome proliferator-activated receptor (PPAR) and liver X receptor (LXR) families of nuclear hormone receptors, respectively ( 14, 15). In addition to their role in lipid metabolism, PPARα and PPARγ are also anti-inflammatory and antiatherogenic ( 16). The anti-inflammatory action of PPARβ does not appear to be sufficient for the inhibition of atherogenesis ( 16). The fatty acid binding protein aP2, found in lesion macrophages, appears to influence atherogenesis by competing for the fatty acid ligand of PPARγ, thus influencing such inflammatory gene activity as cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) ( 17). Cross-talk between the PPAR family and the LXR family may also be important. PPAR increases LXR activity, although this is not obligatory for all of the antiatherogenic influences of PPARγ ( 16). Several studies have suggested the reciprocal regulation of the lipid efflux pathway in macrophages and the inflammatory phenotype of these cells. LXR agonists increase the expression of apolipoprotein E (apoE), apoC-II, and ABCA1 in macrophages, whereas they reduce the expression of iNOS, COX2, IL-6, and IL-1 ( 18) that have been induced by lipopolysaccharide or bacterial infection. On the other hand, the stimulation of TLR4 or TLR3 results in the downregulation of the LXR target genes apoE and ABCA1 ( 19). Furthermore, LXR-dependent genes have been implicated in macrophage cell survival ( 20). This cross-talk does not require the participation of the adaptive immune system.

Similar to macrophages, there are several subclasses of dendritic cells that are differentiated by their TLR profiles. The major subsets are the myeloid or classical dendritic cells and the plasmacytoid dendritic cells. CD8+ dendritic cells and CD11b+ dendritic cells are additional subtypes. In responding to various microorganisms, dendritic cells produce different cytokine profiles: IL-12, TNF-α, and IL-6 for the myeloid cell; type I interferons for the plasmacytoid cell; IL-12 from the CD8+ dendritic cell; and IL-10 by the CD11b+ dendritic cell ( 21). Classical dendritic cells are highly efficient antigen-presenting cells. The plasmacytoid dendritic cells are much less efficient at presenting antigens ( 22), and the type I interferon they produce induces NK cells to produce IFNγ and promote B-cell differentiation to plasma cells, resulting in the production of immunoglobulins of the IgG class. The origin of these dendritic cell subsets is not clear ( 23), although each may have the capacity to program Th1 or Th2 development depending upon its TLR profile and the antigen dose to which it is exposed ( 24). Like the subsets of macrophages, the dendritic cell subsets produce different profiles of chemokines. The dendritic cell has received relatively little attention in atherosclerosis research, although this is bound to change soon ( 25, 26; see VanderLaan and Reardon in this series). Recent studies also are notable for the interaction between lipid mediators and the behavior of dendritic cells in the atherosclerotic plaque ( 25, 26).

The third major cell of the innate immune system that should be discussed is the NK cell. It effect on atherosclerosis is modest (see VanderLaan and Reardon in this series). The NK cells express some diversity in receptors, and their biological activity is probably the result of the repertoire of stimulatory and inhibitory cell surface receptors ( 4). Among human NK cells, two distinct phenotypes can be distinguished on the basis of their cytotoxicity and cytokine production. The cells that express high levels of CD56 (bright) and low levels of CD16 (dim) tend to produce high concentrations of cytokines, especially IFNγ, but are poorly cytotoxic. Those NK cells that are CD56 dim and CD16 bright are mainly cytotoxic. The first subset represents 10% of NK cells, and the latter represents 90% of the NK cell population ( 27). The reported modest influence of NK cells on atherosclerosis may be related to the fact that the cytokine producers have the major effect on atherosclerosis but are only a small proportion of the total NK cell population ( 28).

In conclusion, this review has drawn attention to a limited aspect of the complexity of the immune network. There is much more heterogeneity among cells of both the innate and adaptive immune systems than was previously supposed. There is also a complexity of communications between the elements of this network. This indicates that many opportunities remain for research to improve our understanding of these systems as they operate in the context of atherosclerosis. A more system-based approach may prove rewarding. The improved understanding will present many possibilities for therapeutic intervention in the process of atherosclerosis.

Acknowledgments

The author thanks Catherine Reardon and Paul VanderLaan for critical reading of the manuscript drafts. The author is grateful to Irena Dopter for her help in the preparation of the manuscript. The work of the author is supported by National Institutes of Health Grants HL-56827 and HL-68661.

Received February 7, 2005.

Revision received February 11, 2005.

# data[].attributes.attachment_link.title
Bridging the innate and adaptive immune systems

# data[].attributes.attachment_link.description
Department of Pathology and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 1To whom correspondence should be addressed. e-mail: getz{at}bsd.uchicago.edu So far in this series of thematic reviews, we have dealt with aspects of the innate immune system in relation to atherosclerosis.

# data[].attributes.body
I didn't read this link entirely. But, I think it may have some points. I'll try to simplify it into main points by tuesday. You guys can have a read in the meanwhile, and post the points you found. Thanks

# data[].attributes.attachment_link.title
Old Meets New: The Interaction Between Innate and Adaptive Immunity

# data[].attributes.attachment_link.description
The innate immune system is an ancient and diverse collection of defenses, including the recognition of pathogens through the use of germline-encoded ...

# data[].attributes.body
-The immune response is the responce which body recognizes and defends itself agains bacteria, viruses and substances that appear foreign and harmful
- The immune system protects the body from possibly harmful substances by recognizing and responding to antigen.

# data[].attributes.body
Innate immunity refers to nonspecific defense mechanisms that react immediately or within hours of an antigen's appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body. The innate immune response is activated by chemical properties of the antigen.

# data[].attributes.body
- antigen-specific immune response.
- The antigen first must be processed and recognized. After recognition of antigens, the adaptive immune system creates an army of immune cells specifically designed to attack specific antigen.
- Adaptive immunity also includes a "memory" that makes future responses against a specific antigen more efficient.

# data[].attributes.body
1. Dendritic cells
- Dendritic cells are members of the innate immune system that are particularly efficient at stimulating T cells to respond to antigen.
- The only cells capable of activating naïve T cells, and they can load endocytosed antigenic peptides on both MHC class I and MHC class II molecules, allowing presentation to both CD8 and CD4 T cells.
- Dendritic cells detect danger signals within the tissues and transmit this information to T cells. Pathogens and tissue insults of many kinds are translated into a common result which is the activation and maturation of dendritic cells.
-  Dendritic cells pass on a remarkable amount of information to T cells about the type of insult that prompted their maturation. This information affects whether a T cell will respond to antigen, how it will respond, and likely where it will go to respond.
2. Natural killer cells
- NK cells lack the Toll cell receptor (TCR) for antigen recognition and possess the ability to kill tumor cells or host cells infected by virus.
-  NK cells do not require prior contact with antigens to develop cytolytic properties, though NK cells can acquire specificities using their Fc receptor that binds to IgG-coated target cells. NK cells use numerous pore cell toxins.
-T cell, particularly CD4+ cells, can stimulate NK cell functions. Therefore, NK cells, though members of the innate immune response, have a number of ways of interacting with adaptive immune responses

# data[].attributes.body
~the state of protection from infectious disease, it comprises of both less specific and a more specific component

# data[].attributes.body
~ the reaction is less specific
~it provides the first line defense against infection
~most of compponents in innate are present bfore the onset of infection
~the first barriers in innate include the skin, the mucosal membranes, HCL, lysozyme in tears

# data[].attributes.body
~it capable in recognizing and selectively eliminate specific foreign microbes or antigens
~have 4 characteristics; antigenic specificity, diversity, immunologic memory and self nonself recognition
~2 major groups of cells are involves; lymphocytes (B and T cells) and APC

# data[].attributes.body
sooooo, i read from ref book, it stated that both innate and adaptive immune systems do not operate independently. meaning that, they need to cooperate with each other haha. as they will function as a highly interactive and cooperative system. so that the combined response will be moreeee effective than either branch could produce by itself.

# data[].attributes.body
eg given in the book, cooperation in the encounter between mO and microbes. interaction between receptors on mO and microbial components will generate soluble proteins (cytokines) that stimulate and direct the adaptive immune responses, facilitating the participation of the adaptive immune system in the elimination of pathogens.

# data[].attributes.body
As we all know, animals are under constant threat of invasion by a diverse range of microorganisms that seek to enter the body and exploit its resources for shelter and food. So, immune system is the detection and destruction of invading microorganisms. It will prevent the animals from having any infection or diseases that caused by the microorganisms. Basically it involved two systems which are innate and adaptive immune systems.

# data[].attributes.body
Innate immune system is the protection within the first few days of microbial invasion. The macrophages and neutrophils are responsible for this but they cannot always eliminate infectious organism and there are some pathogens that they cannot recognized.

# data[].attributes.body
Adaptive immune system is responsible for longterm protection. There are two major types which are antibody direct against extracellular invaders and cell-mediated immunity against intracellular invaders. Adaptive immune system are complex and must very carefully regulated. It involves three major populations of lymphocyte which are B cells, regulatory T cells and effector T cells.

# data[].attributes.body
From what I read, the innate and adaptive immune system are related with each other. For example, the phagocyte known as antigen presenting cell because after engulfing the invading microbe, it displays pieces of protein from the microbe, called antigens, on its surface, on what is known as the major histocompatibility complex (MHC) molecule. This alerts the adaptive immune system and allows cells known as T cells to recognize an infected cell.