Haematology and immunology

 

Often any bacterium is known as or described as either a pathogen, virus or any other microorganisms that are able to cause a disease. Our immune system works as a defence mechanism that helps protect our body from these pathogens. In our immune system there are two parts; the innate immune system and the adaptive immune system.

 

The adaptive immune system:

Our adaptive immune system is a form of defence that is antigen-specific. If the pathogen is not effectively destroyed within the innate system, the adaptive will start to respond. This response can take up to 7 days to occur. Even though this response can take longer to occur than the innate system it is often more accurate in being able to target the pathogens. The adaptive system is also able to recognise specific antigens, this means that if it comes across the same antigen again it can respond to it much more quickly. The adaptive system also uses mechanisms such as the cellular and humoral mechanism. Cells that are a part of the adaptive immune system are T-lymphocytes and B-lymphocytes.

 T-lymphocytes produce bone marrow and mature in the thymus, they are also activated through antigen presentation, dendritic cells or by direct contact with pathogen cells. Once these cells are in the thymus they go through a range of processes. This starts with positive selection where it is determined if the T-cell is able to interact with the MHC cortical epithelial cells (CES’s). The T-cell receptors will then interact with MHC I and CD4 will interact with MHC II. The cells that are not able to do this will then die 3-4 days later. After this the cells can then travel to the medulla where the next set of processes can happen. The next process that happens is known as negative selection, this is carried out by cells such as dendritic cells and macrophages. These cells help to get rid of the T-cells that have a high affinity for self cells of the human body. The T-cells that make it through this process are then able to undergo the differentiation into specific cells. These cells are; T helper cells, T killer cells, T suppressor cells, Follicular T cells, regulatory T cells, memory T cells and cytotoxic T cells.

B-lymphocytes also produce bone marrow, they mature in the bone marrow and they are activated by the T-helper cells. Once these cells have developed from the stem cells they go through negative selection, where all the self attacking cells are killed. The B-cell will then go on and develop into two different types when they are activated. These types are memory B-cells and plasma cells.

 

For T-cells, after the selection process is completely finished, the T-cells will be released into the body in the blood and the tissues. The pathogens will bind because of the receptors on the surface of these cells. The T-cell will multiply once it has been bounded and it will also differentiate into a specialized cell. The new T-cells that have been generated will cause the defence reactions in order to help destroy the pathogen efficiently.

 

For B-cells, the development they go through is a process where they rearrange light and heavy chains of the surface receptors; the glycoprotein receptors are known as immunoglobulins. The structure of an immunoglobulin have antibodies that contain two heavy chains and two light chains that are held together disulphide bridges.

“Immunoglobulins.” Myplace.frontier.com. N.p., 2017. Web. 26 Dec. 2017.

Once these antibodies have been formed and the negative selection process has been completed, the cells will then move to the secondary lymphatic organs. In there they will be activated by the binding of a pathogen. Once they have been activated the B-cells will begin to secrete these Igs, the first of them will be from an IgM form. In plasma these types of Igs are called pentamers, and they are formed from five antibodies that have been conjoined with ten antigen binding sites. This helps allow the binding of multiple antigens but with low affinity. The IgM will also form antibodies and then go through antibody class where they switch and covert the IgM form. The antibodies are monomer units this means that they contain two antigen binding sites which have high affinity. This is the strongest antibody that is found in the blood. There are up to five types of Igs; IgA, IgD, IgE, IgG and IgM.

“Immunoglobulin – What Is And Definition | Health Dictionary.” Beltina.org. N.p., 2017. Web. 26 Dec. 2017.

 

IgA – Is normally found throughout the body on mucosal surfaces, such as; respiratory, gastrointestinal and genitourinary tracts. It provides as a first line of defence against pathogens that are in these areas.

IgD – Is often found in the plasma of the membranes of the immature B-cells and can also be secreted into the blood serum.

IgE – Is also found in the membranes, it is made by the plasma cells and when it is activated it responds to cover parasites and allergies.

IgG – Makes up about 75% of serum immunoglobulins and it is the only antibody that is able to carry out placental transfer.

IgM, Usually found on the surface of B-cells. It provides are strong response to many antigens and it is also in charge of starting the blood clotting cascade when blood transfusions are given to candidates that are unsuitable.

 

 

Innate Immune System

Our innate immune system does not respond to specific antigens, this makes it nonspecific and it is the first act of defence we use as humans because it is what we are born with. Our innate immune system is able to respond to all pathogens that are detected within our bodies. This system often occurs and responds to pathogens either immediately or within a very short timescale. Some vital parts of our innate immune system are the; epithelial barriers, cellular mechanisms and humoral mechanisms.

 

Below are the components that make up the innate immune system:

 

Skin

In the innate immune system the skin acts as a physical barrier, so that the pathogens are prevented from entering the bloodstream.

 

Natural microbial flora

There is roughly 1014 bacterial cells on the body, which means there are more bacterial cells on the  body than there are cells that make up the body. Natural microbial flora can be found on our skin and mucous membranes throughout the body, often they are harmless to us and we co-exist with them. Often flora is referred to the ‘friendly; bacteria that is competition with the other pathogens that are harmful to us.

 

Mucus

In the mucous membrane there is mucus that mainly acts as a barrier against pathogens. It also helps to trap pathogens and the substance it is made up of contains defensins which can help to destroy the pathogens or slow the growth of them.

 

Cillia

There is motile cilia that is able to move in a motion that is wave like and this helps it to move mucus and pathogens into other areas of the body, such as the lungs or the respiratory tract. 

 

Tears

Tears are made up of enzymes, known as lysozymes that help to break down the cell walls of the pathogens. 

 

Blood clotting cascade

In the blood clotting cascade there are two different pathways. These are known as intrinsic and extrinsic pathways. Even though at first they both begin as two separate pathways. Eventually they begin to come together to become one pathway. In the extrinsic pathway the tissues outside the blood vessels that have been damaged will activate it so that it occurs. Depending on how much damage has occured will affect how much factor III is produced. These will then mix together with some calcium ions which will then cause factor VII to activate into VIIa. On the other hand there is the extrinsic pathway, this pathway activates when the elements of the blood stream, such as XII comes into contact with collagen. This causes it to become activates into XIIa. HMW, kininogen, prekallikrein and XIIa work to help further activate factor XI into factor XIa. These factors will then mix with calcium ions which will help activate factor IX into IXa. There will also be platelets that will release PF3 and factor VIII which will help to activate to VIIIa. Then VIIIa and IXa will mix in order to form factor 5 and this activates tenase. A common pathway will start to form when both of the pathways join together. Factor X will be activated by the VIIIa or tenase that is released into Xa. Calcium, Va and Xa will then catalyse factor II (prothrombin) into factor IIa (thrombin). This will then cause factor I (fibrinogen) to change into factor Ia (fibrin). The fibrin strands will then begin to join together that will form a net like structure. The thrombin will also help to activate factor XIII and the fibrin will be the stabilizing factor. This allows blood clots to form.

“Simple Coagulation Cascade With Mnemonics | Epomedicine.” Epomedicine. N.p., 2017. Web. 23 Dec. 2017.

 

Inflammation

In a case where the pathogens make it past the barriers that are put up by the immune system, an inflammatory response will kick in. In the connective tissue there are damaged cells that will release chemokines into interstitial fluid and the mast cells will release a histamine to the area of infection and then they will begin to surround the blood vessels and capillaries. This is what causes the walls of the arterial to expand and the walls of the venal to constrict. This helps to increase the blood flow and it also helps the endothelial cells in the capillaries to separate from each other, this allows phagocytes to move to the infection site and then attack the pathogens.  In inflammation there are three stages; acute inflammation, sub-accuse inflammation and chronic inflammation. The acute inflammation stage lasts up to 1-3 days and often occurs within seconds once tissues damage is recognised. The damage that occurs may often be a result of the damage that has occured within the immune system. In this stage there is often an increase in the blood flow through the dilation of the blood vessels that are supplying. There is also often an increase in the permeability of the capillaries that are surrounding it. Factors like this can result in redness and swelling in the areas that are infected. Neutrophils will then begin to move from the blood vessels to the tissue that has been damaged. They are able to get to the area of infection with the guidance of chemokines and C5a peptides of the complement system. The sub-accuse inflammation stage can last up to 3 weeks after the 4th day. This stage is the transition period between the acute and chronic inflammation stages. The chronic inflammation stage will start to occur once inflammation has been persistent. The cells that are the primary cells for chronic inflammation are macrophages and T-cells and they will begin to produce cytokines and enzymes that will damage the area of tissue that is already damaged this will then lead to tissue fibrosis. 

 

Phagocytosis:

This is carried out by a specific white blood cell such as neutrophils,monocytes, macrophages, mast cells and dendritic cells. In phagocytosis there are five stages. The first stage is known as chemotaxis and it is where the phagocytes move towards the pathogens through the chemicals that are detected because they have been released from the foreign body. Stage two is where the phagocyte will attach itself to the pathogen through the receptors known as antibodies.  In stage 3 the phagocyte will engulf the pathogen in a vacuole that is known as a phagosome. Lysosomes which are vesicles will then join to the phagosome so that a phagolysosome can be formed. In stage 4 the lysosome will release digestive enzymes such as lysosomes and proteases and toxic compounds which will then help to kill the bacteria. In stage 5 the bacteria’s antigen is transported through the histocompatibility complexes (MHC). Then it is displayed on the surface of the cell of the phagocyte. MHC’S are there to help join peptide components of pathogens and then to present them on the cell surface of a phagocyte. This then allows specific T-cells to be activated and then the pathogen with the same antigen can be recognized in the future.

 

Cytokines:

Cytokines are small proteins that work as meditators between the immune system cells. They often can influence many cellular functions such as; proliferation, differentiation and apoptosis. Cytokines can be produced by many different cells from both the innate and adaptive immune system.

 

Complement system:

This is a cascade reaction that happens only when one of twenty serum proteins have been activated. There are three main roles of this system; to start or enhance the inflammatory responses, to act as opsonins to help enhance phagocytosis and to help destroy the membrane of the pathogen through membrane attack complex (MAC). MAC causes the bacteria cell to burst because of the small pores that it releases into it. There are three pathways of the complement system and they are the; classical pathway, lectin pathway and the alternate pathway. The classical pathway is the binding of an antibody-antigen complex to C1, this causes a conformational change. Which activates C1r and C1s. This then causes the C4C3 to cleavage, this causes C3a to activate mast cells while the C3b cells bind to the cell surface of the pathogens to help to enhance opsonization. The lectin pathway, is very similar to the classical pathway. This pathway is activated with opsosin. It binds to mannose on the surface of the pathogen and this activates MASP1 and MASP2. The alternate pathway is activated through hydrolysis of C3 in order to produce C3. This makes it much more reactive and it also binds to Factor B.

 

 

 

 

 

 

 

 

Immune response to different pathogens:

 

 

The human immune system has the ability to respond to different pathogens in different ways.

For example, the way the immune system responds to a bacterium would be different on how it reacts to s virus. An example of a few pathogens and how the immune system reacts to them is followed below.

 

 

Rabies

 

Rabies is a known virus that is usually spread by the bite or scratch of an animal. This virus has two forms, one type is known as “furious rabies” and sufferers of this type normally die within a few days and the cause of death would be down to cardio- respiratory arrest. Whereas the second type of this virus is known as ” Paralytic rabies” the process of this type of the virus is not as aggressive as the previous form mentioned above, this form eventually paralyses the sufferer and it from there slowly develops into a coma which leads to death as it becomes too late to treat the virus due to misdiagnosis.

 

The human immune system responds to rabies by identifying an antibody in the serum and it is sent to the central nervous system as that is the site that needs it the most as that is where the rabies virus attacks first the most.

The virus travels via the nerve pathways of the muscles to the central nervous system, it then replicates quickly and begins to spread throughout the brain. The brain will then become inflamed and many parts of the CNS will be affected. Treatment is given by a specific immunoglobulin that is passive immunisation and also by the administration of a normal vaccination this is known as active immunisation. The immunoglobulins build together to bind to their target, this prevents the virus from being able to penetrate into cells, this gives the immune system time to react and destroy the virus. 

 

E.coli

Is a bacterial infection that is caused by the E.coli O157 strain. It can be caught by eating food that has been infected such as raw leafy vegetables, undercooked meat or raw milk products. It can also be caught by having interactions with other infected animals or people such as by touching them, or it can be caught by drinking water that isn’t clean or being in water that isn’t clean. The symptoms of this infection are; fever, stomach cramps, vomiting and diarrhea.

When we have E.coli our body tries to get rid of the bacteria by trying to have it exit the body either through vomit or excretion. Often it will leave the body in a week naturally as there is no official cure for it, but sometimes it can lead to hemolytic uremic syndrome (HUS), this can cause the blood cells to break up which can cause anemia.

 

Haemoglobinopathies

Haemoglobin is a protein that transports oxygen molecules so that it can be found within red blood cells. It contains four polypeptide chains that are held together by disulphide bridges, hydrogen bonds, ionic bonds and Van De Waal forces. Each of the chains has a haem group that is able to bind to a single oxygen molecule. The fetal haemoglobin has a different structure where it has chains two ? chains and two ? chains. This is because the Y chains have a high affinity for oxygen, this means the foetus does not need to compete with the mother. Once the child is born, a gene switch will happen and the Y chains will become ? chains.

There is a disorder that affects the structure, function and production of haemoglobin, including; thalassemia syndromes and structural Hb variants, this disorder is known as haemoglobinopathies.

There are two main types of thalassemia; ?- and ?- thalassemia. There are three main types of Hb; HbS, HbE and HbC.

 

Haemoglobinopathies are disorders that affect the structure, function or production of haemoglobin; these include thalassemia syndromes and structural Hb variants. The two main types of thalassemia are ?- and ?- thalassemia. Thalassemia is caused when there is a gene defect that is caused by Hb synthesis disorder. The three main types of Hb are HbS, HbE and HbC. Thalassemia is caused when gene defects cause Hb synthesis disorders.

 

ANEMIA:

Anemia develops when your blood doesn’t have enough healthy red blood cells or haemoglobin. It can cause individuals to feel fatigue because their blood isn’t getting to their organs properly so it makes it hard for them to function. Anemia affects hemoglobin because it breaks up our red blood cells and can cause us to have a low platelet count. This can affect on how our blood clots so that means there could be a reduced blood flow to vital organs. This can also affect if our body gets enough oxygen or not. Which can also make us more vulnerable to catching more diesears because it weakens our immune system.

 

 

Homeostasis and Thrombosis

Haemostasis refers to the blood that goes through a damaged blood vessels, in this process there are vascular, platelets plasma factors. The vascular factors are that the endothelial cells of blood vessels that function normally will inhibit blood clotting through the secretion of fibrinolytic heparin molecule and thrombomodulin. A blood vessel that has become damaged will temporarily stop these secretions from happening in order to start coagulation and the formation of the clot. Vasoconstriction will also occur for a small amount of time to help reduce the blood flow to the area that is injured.

Platelet factors would be that a structure known as ‘platelet plug’ will begin to form straight after there has been damage to the blood vessel. Within the first sixty seconds fibrin strands will be disbursed, this will produce a platelet plug that is fully formed within minutes.

Plasma factors would be that the blood clotting cascade will occur and then scab that would form over the wound.

 

Thrombosis is when the blood clot starts to form within the blood vessel which prevents circulation of the blood. However, the blood vessel is not damaged by the clots that are formed within it. There are two types of thrombosis; deep vein and arterial. In deep vein thrombosis the formation of the clot is deep within the veins of the body and this usually happens within an individual’s legs. If it is left untreated then the clots can cause an pulmonary embolism. In arterial thrombosis the formation of the clots are within the arteries, this means there could be a restriction in the blood flow to vital organs. Thrombosis can be caused by many different causes, such as; high blood pressure, High (LDL) cholesterol, arterial fibrillation, inactivity and altitude.

 

This disorder can cause many different symptoms such as; redness, swelling and pain in the area that has been infected. In order for this disorder to be diagnosed an MRI or ultrasound scan can be used. In order to treat this disorder, surgery may have to be undertaken, in order to remove the clot.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

References:

 

 

Cold, Flu ; Cough et al. “The Basics Of Anemia.” WebMD. N.p., 2017. Web. 21 Dec. 2017.

 

“E. Coli Infection.” nhs.uk. N.p., 2017. Web. 20 Dec. 2017.

 

Easmon, Charlie. “Rabies.” Netdoctor. N.p., 2018. Web. 20 Dec. 2017.

 

Cold, Flu ; Cough et al. “The Basics Of Anemia.” WebMD. N.p., 2018. Web. 21 Dec. 2017

 

“Introduction To Immunoglobulins | Thermo Fisher Scientific.” Thermofisher.com. N.p., 2017. Web. 22 Dec. 2017

 

“Immunology Pathways And Posters.” Abcam.com. N.p., 2018. Web. 22 Dec. 2017.

 

“Introduction To Immunology Tutorial.” Biology.arizona.edu. N.p., 2017. Web. 21 Dec. 2017.

 

“Khan Academy.” Khan Academy. N.p., 2018. Web. 22 Dec. 2017.

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