Essay on Innate Immune Response

Immunity is defined as the protection and resistance against infection by microorganisms. Innate immunity is the nonspecific defense mechanism that is immediately activated, or within minutes of the appearance of the antigens in the body, therefore, the principal function of the innate defenses is to combat harmful pathogens. The innate immune defense mechanisms are discussed below.

Surface or Physical Barriers

Skin: The skin is a heavily keratinized epithelial layer that is resistant to most of the toxins, weak bases and acids and some bacteria. The skin secretes acidic substances that inhibit the growth of bacteria. For example, sebum inhibits the growth of bacteria due to its toxic chemicals.

Mucous membranes: Mucous membranes cover all the body cavities that extend to the external body parts including the respiratory tract, eyelashes, some body hair, the digestive and respiratory tract. The saliva and lacrimal fluid are composed of lysozyme enzyme that destroys bacteria. The mucous membranes secrete sticky mucus that prevents microorganisms from entering the respiratory and digestive tracts. The respiratory tract membranes are structurally adapted with small hairs coated with mucus to trap any foreign particles away from the lower respiratory tracts.

Internal barriers

Surface barriers can be ineffective when there are cuts thus causing the invasion of the internal tissues. Therefore, this triggers the need for the internal, innate barriers to the microorganisms. The most common internal barriers include the following.

Phagocytic cells (Phagocytes)

Macrophages: The term Phagocyte implies engulfing cell. The common phagocytes are the macrophages which roam the entire body and engulf any foreign material such as alveolar macrophages of the lungs. However, they can be stationary like the microglia cells in the brain. The macrophages result from monocytes which leave the blood circulatory system into the tissues and grow. The ability to move outside the bloodstream enables them to engulf pathogens with small limits. Microphages also do secrete cytokines as a way of signaling the addition of the cells to an area under attack by the pathogens

Mast cells: Mast cells are significant in the healing of wounds and acts as a barrier against pathogens through the inflammatory response. These cells are found both in the mucous membranes and connective tissues. The activation of the mast cells causes them to secrete cytokines and granules which in effect produce the inflammatory cascade. A chemical such as a histamine dilates the blood vessels causing an increase in blood flow to the infected area thus increasing the concentration of the cells to the area. The secreted cytokines trigger the rest of the immune cells to be ready for the impending threat or to flow to the field of infection.

Neutrophils: These are the abundant types of white blood cells. Nearly 100 billion neutrophils are released from the bone marrow of a healthy adult on a daily basis. Neutrophils contain granules hence classified also as granulocytes. The granules are very poisonous and can kill bacteria or fungi on contact. Also, neutrophils exhibit phagocytic behavior when exposed to infectious materials. The neutrophils secrete chemicals that can destroy cells including themselves. However, the drawbacks of these cells are that they can cause tissues to become cancerous in case continued activity.

Eosinophils: Eosinophils are weak phagocytes that target parasitic worms. They constitute only 1-6% of the white blood cells but are found in most of the body parts such as, in the spleen, lymph nodes, and uterus. The cells release very toxic chemicals which kill bacteria and parasites. However, the chemical substances can damage tissues during allergic reactions hence the reason for the regulation of the release of substances to prevent unnecessary damage to the tissues.

Basophils: Just like the mast cells, basophils secrete histamine that attacks parasitic worms. They are also granulocytes. Histamine makes the basophils and mast cells significant in any allergic response.

Natural killer cells: They are produced in the blood and lymph and are classified under the large granular lymphocytes. The natural killer cells detect sugars but are not phagocytic, and they promote the inflammatory response due to the chemicals they release. They attack pathogens by destroying the infected cells to avert any further spread. Such a case happens by the sign produced by the infected host cells to the natural killer cells to kill them.

Dendritic cells: Dendritic cells are found in the tissues and are linked to the surface through the skin, the mucous membrane of the nose, digestive tract, and stomach. The dendritic cells are strategically located at the points of common infection, and thus they quickly detect pathogens and trigger the immune system for action. They also act as a link between the nonspecific and the adaptive immune system.

The complement cascade/system: This is a system that complements other parts of the innate immune response but can occasionally work with the adaptive immune system. The complement system is efficient both when in an active or inactive state. The proteins contained in the system circulate in the blood when inactive, and form a complement cascade when the proteins are activated through the following stages.

Opsonisation: This is a process of coating the pathogens with its proteins thus increasing devotion. For the pathogens to be detected, the passways have antigens that send messages of the presence of pathogens. Then opsonisation engulfs the infected cells and notices any other infected cells with similar antigens.

Chemotaxis this is the detection and response of macrophages to a substance signal. This step employs cytokines and chemokines to draw phagocytic cells to the place of infection to destroy the pathogens.

Cell Lysis. Lysis is the destruction of the lining of a cell. The protein components of the complement cascade perforate the lining of the cells of the pathogens thus weakening their ability multiply.

Agglutination. This stage groups and binds the foreign cells by using antibodies. The cells of the immune system attack and destroy the grouped pathogens and thus inhibits their infection and spread. The circulation of the cells of the immune system continue, and when pathogens are detected, they are clustered in the area of infection and attacked once.

Pellino Protein

Pellino protein is a molecule that interacts with other multiple members of a signaling pathway combining them into complex structures.

Types of Pellino Proteins and their Differences

The available evidence shows that pellino proteins majorly function. Almost similarly as scaffold proteins (Ceppi et .al, 2009).

KSR Proteins: This type of protein uses the MAPK pathway in the gathering of the RAS-ERK pathway. One amongst scaffold proteins that have been identified to be in this pathway is the KSR (Douziech, 2006). It best regulates the pathway and groups many proteins it comes across in the channel.

MEKK1 Proteins: Similarly, this type of Pellino protein utilizes the MAPK pathway and functions to gather and localize the death receptor signalosome.

AKAP Proteins: These proteins use the PKA pathways. Their primary purpose is to organize phosphorylation through the PKA to the targeted areas. The PKA proteins have a similar ability to bind its governing subunits due to their similar structure; however, they can still bind enzymes that are of different structures.

AHNAK-1 Proteins: These groups of proteins use the calcium signaling pathway in the gathering of the calcium channels. The pathway of calcium signaling is significant in the practical operation of the immune cells. AHNAK-1 has a unique ability to localize calcium channels around the membrane lining thus enabling it to become active in calcium signaling (Tu et. al, 1998). AHNAK-1 also combines calcium channels with phospholipase only in the non-immune cells.

HOMER Proteins: Homer proteins also utilize the pathway of calcium signaling to inhibit NFAT activation. These families of proteins strive with calcineurin to combine the NFAT terminus in T cells (Huang et. al, 2008). Such strife enables the HOMER proteins to significantly reduce the production of cytokine (IL-2) due to the ability of NFAT activation. On the other hand, the HOMER proteins normalize the calcium signaling in neurons.

NLRP Proteins: The NLRP are in the innate immune signaling pathway to mainly gather the inflammasome. The NLR is a family of receptors that operate as scaffolds by gathering the inflammasome.

Functions of Pellino Proteins

Research shows that all pellino proteins function as scaffold proteins due to their ability to interact with the components of Complex II (Yu et al. 2002). These features include the list discussed below.

Tethering signaling components

Tethering signaling components is an essential function of the Pellinos. The pellinos gather signaling parts of a cascade into complexes. Signaling specificity is improved by the gathering through the prevention of needles interfaces among the signaling proteins. For example, the protein kinase is bind by a pellino protein thus enhancing kinase phosphorylation. Also, scaffold tethering is activated through the activation by the various reactions leading to numerous modifications. Pellino proteins may also result in allosteric changes due to its catalytic nature during the interaction with signaling proteins. The variations can positively or negatively affect the signaling proteins such as the Ste5 scaffold.

Restriction of the signaling components in the cell

Pellinos just like scaffolds restricts the signaling reaction to a particular portion of the cell. The process helps in the production of signaling components. For example, the AKAPs aim the PKA to distribute it to various areas within the cell.

Organizing positive and negative feedback

Most of the assumptions on how the pellinos coordinate feedbacks are based on both mathematical demonstrations and devised scaffolds. The improvement of Kinase specificity and limitation of signal amplification takes place when all the three kinases are combined and thus restricting kinase phosphorylation to a single downstream target. Such a case also explains the reasons behind the stability that exists between the scaffold and the kinase interactions.

Shielding the right signaling proteins from inactivation.

Enzymes always inactivate the signaling pathways or stimulate the ruin of signaling components. Pellino proteins protect the activated signaling components from enzyme inactivation or deprivation. For instance, pellino proteins insulate kinases from competitive inhibitors.

The Structure of Pellino Protein

When pellino-1,2 and 3 proteins are mapped to chromosomes 2, 14 and 11 respectively, two types of Pellino-3 exist in human beings namely Pellino 3a and 3b. The former model is the longest with seven coding exons while the later one is the shortest without exon-2. However, dogs have pellino-3 without some components of exon-1 and 3. When the human and rat pellino-3a are blasted against the mouse genome, no alleged mouse pellino-3a and exon-2 is found. Pellino 1 and 2contains six coding exons which are homologous to the exons found in 3b. The Drosophila has eight coding exons like that of humans 3b, 2 and 3 though split into four different exons. The analysis of the EST sequence shows that mRNAs of the pellino in mammals are found in most of the organs with a variation in the levels of expression in each organ. Such a case implies that the distinct proteins have specific tissue functions.

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