Health and Disease

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Q3 (3.2)

 Explain the process of phagocytosis using a series of labelled drawings. Justify phagocytosis as a defence mechanism?

Pathogenic organisms such as bacteria and viruses need to enter the body of their host before they can cause harm. Evolution by natural selection has selected hosts adapted to defend themselves against such invasions.  The body possesses many mechanisms that have evolved to prevent of pathogenic organisms include the non-specific defences and the specific defences.  The non-specific defences consists of the primary line of defence and the secondary line of defence, so if the primary line of defence  fail in preventing the entry of any pathogen the secondary line of defence will take the responsibilities to prevent them from gaining a foothold in the body and destroy them if they penetrate to the deeper tissues.

The blood consists of fluid called plasma that contains different constituents such as red blood cells or erythrocytes, white blood cells (WBC) or leukocytes and platelets. The mechanisms are related to the defence mechanism of body provided by white blood cells (WBC) or leukocytes. The leukocytes are divided into granulocytes and agranulocytes on the basis of granules (are tiny sacs containing enzymes that digest microorganisms) in their cytoplasm. Granulocytes contain three types of blood cells (neutrophils, basophils and eosinophil) and agranulocytes contain two types of cells (lymphocytes and monocytes).

After infection the number of WBC increase in the blood during the initial phase of infection. At this stage they are phagocytic in nature. Phagocytosis is specialised white blood cells in the blood and tissue fluid of non-specific secondary line of defence that refers to engulfing of large, solid particles often the engulfed particles are pathogens and destroy them. The stages of the phagocytosis are:-

• Stage 1 : Activation of the phagocyte; resting phagocytes are activated by the inflammatory mediators such as bacterial products like bacterial protein, capsules and acids,etc. It is also activated by complement proteins, inflammatory response. The inflammation is a non-specific response to any trauma occurring to tissues and can be controlled by chemical substance called histamine released when the tissue is infected to increase the capillary permeability, enable the phagocytic white blood cell such as neutrophils and monocytes to enter the infected area. As a result, the circulating phagocytes produce surface glycoprotein receptors that increase their ability to adhere the inner surface of capillary walls, enabling them to squeeze out of the capillary and be attracted to the site of infection.
• Step 2 : chemotaxis of phagocytes; chemotaxis is the movement of phagocytes towards an increasing concentration of some attractant such as bacteria l products (capsules, bacterial protein and acid) and phospholipids released by injured host cells or towards particular Chemical . Some microorganisms such as influenza a viruses, mycobacterium tuberculosis blocks the chemotaxis .
• Step 3:- Attachment of the phagocyte to the microbe ; attachment of microorganism is necessary for ingestion as the phagocytosis won’t happen unless the cell is in physical contact with the particle it wants to engulf. The cell surface receptors used for the phagocytosis depends on the type of the cell that is going the phagocytizing and the most common ones are opsonin receptors  and antibodies. The opsonins are protein molecules   that attach to the antigens on the surface of the pathogen. Some opsonins are not very specific so they can bind different pathogenic cells. The opsonins role is to enhance the ability of the phagocytic cells to bind and engulf the pathogen. The process of enhanced attachment is also opsonisation.
• Step 4 :-  ingestion; after attachment the plasma membrane of phagocyte extends short projections known as pseudopods which engulf the foreign materials or microorganisms. This process is known as ingestion and during the ingestion, an electron pump brings proton (H⁺) into the phagosome. This lowers the pH within the phagosome to 3.5-4.0 so that when a lysosome fuses with the phagosome. This is the optimum pH for the acid hydrolases to effectively break down cellular protein. The acidification also releases enzymes that can kill microbes.
• Step5:- Digestion; phagocytes contain membranous sacs known as lysosomes produced by the Golgi apparatus that contains digestive enzymes called hydrolytic enzymes and bacterial chemicals. So after engulfment phagosome comes in the contact with the lysosome a single layered large structure is formed which is known as phagolysosome. The pathogen or the foreign materials are destroyed by the contents of phagolysosomes within 10-30 minutes.
• Step 6:- Egestion; the microbial fragments and the dead phagocyte is eliminated from the cell and collected in an area of infection to form pus.

The granulocyte (neutrophils) and the agranulocytes (monocytes) are two types of the specialised phagocytosis cells.

The neutrophils are the most abundant type of granulocytes and the most common phagocytes that are formed from stem cells in the bone marrow. They are travel in the blood and often squeeze out of the blood into tissue fluid. The neutrophils are recognised by their multi-lobed nucleus and are short-lived, but they are released in large numbers as a result of an infection. The neutrophils bind to the opsonin attached to the antigen of the pathogen then the pathogen is engulfed by the phagocytosis forming a phagosome. The neutrophils contain large number of lysosomes so the lysosomes fuse to the phagosomes and release the hydrolytic enzymes into it to digest the microorganisms. After digestion the harmless products can be absorbed into the cell. The neutrophils usually die soon after the digestion of few pathogens so the dead neutrophils are collected in the infection area to form pus.

The monocytes are agranulocyte type of specialised phagocytosis white blood cells. Monocytes are formed in bone marrow from pluripotent stem cells; their direct precursor cell is promonocyte that derives from the monoblast. The monoblast cells divide and mature into monocytes in the bone marrow. Then monocytes enter the blood circulation and present in the blood vessels for relatively long time. After they migrate to the lymph nodes which are a network of major sites of B and T lymphocytes and other WBC, present in the body tissues. Most of the monocytes are present in lymph nodes where they mature and enlarge in size to become macrophages. Macrophages are specialised large phagocytic cells of the immune system that are formed in response to an infection or accumulating damaged or dead cells. The macrophages are playing an essential role in initiating the specific responses to invading pathogens, as they release chemicals called monokines to stimulate the B-lymphocytes to differentiate and release antibodies. The macrophages are phagocytic cells they attach to the pathogen and engulf them but they do not digest the pathogen fully. The antigen from the surface of the pathogen is not digested by the macrophages so it is saved. So it moves to a special protein complex on the surface of the cell that insures the antigen is not mistaken for a foreign cell. The cell becomes an antigen-presenting cell. The antigen-presenting cell exposes the antigen of the pathogen moves around the body where it can come into contact with specific cells that can activate the full immune response. So the other cells of the immune system such as T and B lymphocytes can recognise the antigen of the pathogen in the Antigen-presenting cell.  These antigen-presenting cellshave an important role to increase the chances for antigen and immune cells to contact.

Q4 (3.1,3.3,4.4)

1. Explain the process of the blood clotting and justify how it is a defence function.

The body is covered by the skin, which is the main primary first line of defence and for the skin to be protective it must be complete. Lacerations or abrasions damage the skin and injury the blood vessel. When this occurs, the body open to infections and loss a lot of the blood. The body must prevent the excessive loss of blood by the formation of clots, making a temporary seal to prevent infections, and repairing the skin. Blood clotting, which is also known as coagulation is a complex process to prevent excessive blood loss by forming clots but also to make sure that these clots are not be formed in the blood vessels where they are not needed.

There are several process involved in clotting of the blood so when the blood vessel is injured, the walls of the blood vessel contract to limit the flow of the blood to the damaged area. Then a small blood cells called platelets stick to the site of injury and spread along the surface of the blood vessel to stop bleeding. At the same time, chemical signals known as granules are released from small sacks inside the platelets; this process is known as secretion. These signals will attract other platelets cells to the area of injury and make them clump together to form what is called a platelet plug, this process known as aggregation. On the surface of these activated platelets, there are calcium ions and at least 12 factors known as clotting factors. The clotting factors are proteins that activate an enzyme cascade and working together in series of complex chemical reactions called coagulation cascade; where the thrombokinase enzyme change the prothrombin to thrombin in the presence of calcium ions. Thrombin combines with soluble fibrinogen found in the blood and forms insoluble fibrin. The insoluble fibrin forms thread like structures that form a sticky mass and this forms a network of a sticky substance at the cut or the damage area of the blood vessel. This sticky mass on the cut becomes denser and denser and is known as clot and act as mesh to stop the bleeding.

The coagulation factors flow in the blood in an inactive form, but when blood vessels injured is secrete a substance called thromboplastin which initiates the reactions that result the formation of the clots.

Once the clot has formed, it begins to dry out and form scab. As the scabs dries, it shrinks and drawing the sides of the cut together to make a temporary seal, under which the skin is repaired. The first step is the deposition of fibrous collagen under the scabs. The epidermis layer contains stem cells which are undifferentiated so then they divide by mitosis division and migrate to the edge of the cut where there they become specialised into new skin cells. New blood vessels are also formed to supply the new tissues with oxygen and nutrients. Later the tissues formed contract to help draw the edges of the cut together so that the repair is complete and as the new skin is formed the scabs are released. This process called skin repair.

2. Differentiate between the role of B and T- lymphocytes, using diagrams (attached to the assignment)

Lymphocytes are a-granulocytes type of the white blood cells in the specific third line of defence, which produced in the bone marrow but after the production they leave the bone marrow. Some of the lymphocytes travel to thymus where they develop and become specialised into subset of T-lymphocytes cells; each have different function. While the other lymphocytes travel to lymphoid tissues like lymph nodes, where they develop and become specialised into B-lymphocytes cells. Although both types of lymphocytes (T and B cells) have a large nucleus and specialised receptors on their surface membrane, identify the invaders and attack (specific immune responder), and both produced in bone morrow,  they mature in different places  and they play different roles in helping the body to eliminate microorganisms.

The role T-cells :-

After T-cells develop in the thymus, they differentiate into four main types which are T-killer, T-helper, T-regulator and T-memory cells; each of them has an important function in the immune system. They are either travel around in the blood or lymphatic system or migrate to different organs in the body. But as soon as a specific pathogen with its specific foreign antigen molecules on its surface stimulate the immune system, the immune system start to make the T and B cells to recognize and attack the specific antigen in the pathogen; only certain T and B cells can match and react to a specific antigen.

The helper T-cells release chemicals messengers known as cytokines to trigger the B-cells to develop and differentiate into plasma cells to release antibodies, and also stimulate the phagocytosis by phagocytes. The helper T-cells release also interferon which inhibit the pathogen such as virus replication and stimulates the activity of T-killer.

The T-killer cells will target, attack and kill host-body cells that have become infected by invader or display foreign antigen or are cancerous. Natural killer T cells also produce chemicals known as interleukins that can stimulates the clone expansion of memory T cells. They also release other chemicals to help regulate the immune response and protect against the invaders and tumours.

Regulatory T-cells are also called tregs; T regulatory cells were originally identified as a CD4+CD25+ T cell population with the capacity to stop T-lymphocytes immune response. This is because the T-regulatory cells develop and their CD4 and CD25 cell surface proteins markers are up regulated. The treg cells would effectively stop an immune response after it has begun. This helps to control the immune reaction and shut the immune response after the pathogen has been successfully eliminated to prevent autoimmunity. Autoimmune disease occurs when the immune system start to attack our own normal antigen, possibly because these antigen that are not normally exposed become exposed to attack.

Memory T cells stay around for a long time after immune response has finished providing long-term immunity. In this way they can react quickly without symptoms if the same pathogen appears again and also they multiply to produce a large number of T-cells to remove the pathogen.

The role of B-lymphocytes cells

The B-lymphocytes develop in lymph nodes and travel in the blood. When they come across pathogen the B cells are stimulated. The T-helper release cytokines to stimulate the B-cells into action to produce plasma cells and memory B-cells. Unlike T-cells, B-cells cannot directly attack infected cells. Instated the plasma cells primarily produce proteins called antibodies.

The plasma cells; each plasma cell is specialized to produce a particular antibody – antibody is a specialised protein with receptor that are complementary bind to a specific antigen.  The role of the antibodies is to act as flag on the infected cell so they can easily be recognized by the specialized cells such as T-cells or phagocytes that are responsible for engulf the infected cells and destroy them. The plasma cells disappear after an immune response is complete, memory B cells stay circulating in the body for long time.

The B-memory cells stay in the body for a number of years for faster response without any symptoms if the same pathogen again, the right antibodies are directly produced to help fight them off.

As it shows in the graph, when a person is exposure to an infection for the first time, the concentration of antibodies are very low, but in meantime the B-cells are produced and differentiate into plasma cells to produce the right antibodies for that pathogen; so slowly the number of antibodies is increasing to fight the pathogens, here the person is experience the symptoms and it takes few days to cure. After the infection, the B-cells produce B-memory cells to stay around in the blood for long-term immunity. Later when a person is exposure to the same infection, the immune system will responses very quickly, as the B-memory cells will immediately provide the right antibodies to fight the pathogens, it will provided in large number, therefore the concentration of antibodies will rise up, here the person will not experience any symptoms and won’t take long to cure from the infection.

3. Explain the essential difference between humoral and cellular responses as shown by B and T –lymphocytes.

The immune system distinguishes two groups of foreign substances. One group consists of antigens that are freely circulating in the body; these include molecules, viruses and foreign cells. The other group consists of antigens tagged with the cellular surface protein called MHC; the MHC proteins found on the surfaces of cells that help the immune system recognize foreign substances. can initiate from antigens that have been engulfed but without being fully destroyed (antigen is saved and exposed) .Depending on the kind of foreign invasion, two different immune responses occur; the humoral response (or antibody-mediated response) and the cell-mediated response.

The cell-mediated response ; involves the phagocytes and T-cells  but mostly T-cells and respond to any cell that display MHC protein, including cells invaded by pathogens and tumour cells. The steps of events for the cell-mediated response:-

1. Antigen-presenting cells displaying the antigen of a pathogen to T cells
2. T-helper cells release interleukins to stimulate the activation of T-cells
3. If the MCH and endogenous antigen (virus‐infected cells that are actively synthesizing foreign proteins) are displayed on the plasma membrane, the T-cells divide, multiply, and differentiate into T-killer cells. The T-killer cells attack and kill the cells displaying the antigen.
4.  If the MHC and exogenous antigen (antigens that have been engulfed and broken down) are displayed on the plasma membrane, the T-cells divide and produce T-helper cells. The T-helper cells produce chemical called cytokines to stimulate the cells to produce antibodies that bind to the antigen and also stimulate the phagocytes cells to engulf and destroy the antigen.

The humoral response:-  (‘’humor’’ is a term for body fluid used in medieval) is the immune response that involves the B-cells that recognize the antigen of the pathogen that are circulating in the blood. The steps of the humoral response:-

1. T-helper cells release cytokines to stimulate the B-cells, in some cases, both the chemical messenger and the antigen in the pathogen are required to activate B-cells and start the B-cells division.
2. B-cells divide and differentiate into plasma cells that release antibodies with receptors complementary to the antigen receptor in the pathogen so they circulate around the body, binding to the antigen.
3. B-cells produce memory cells that can provide long term immunity.

Q5 (4.1)

Explain antigen and antibody interaction. Use diagram (attached to the assignment)

Antigens are molecules that can stimulate the immune response. Almost any molecule could act as antigen, but they are usually protein or glycoprotein in the plasma membrane of the pathogen; such as bacteria, viruses or fungi that cause infection and disease. Foreign antigen will be detected by the immune system and will activate the production of antibodies. Antibodies is also called immunoglobulin, are complex protein manufactured by the plasma cells in the immune system. They are released in response to an infection in order to fight against foreign antigens. Antibody molecules are typically Y-shaped with a binding site on each arm and have two distinct regions, which are variable region that have specific shape to the shape of antigen, the other region is the constant region that is same for all antibodies. The binding sites of each antibody have specific shape that is complementary to a particular shape of antigen. Means only antigens that match this shape will fit into them. Therefore the immune system must manufacture one type of antibody for every antigen that is detected. The function of antibodies is to complementary bind to particular antigens and inactive them so that other immune cells can take over, destroy and eliminate theses foreign antigens. This is the specific chemical interaction between the antibodies and the antigens during immune reaction, and is the fundamental reaction in the body by which the body is protected from complex foreign molecules.

Antibodies work in different ways, but most act by attaching to the antigen on the pathogen. There are three main group of antibodies; the opsonin, agglutinins and anti-toxins.

Opsonins are group of antibodies that bind to the antigen so then they can act as binding sites for phagocytic cells to make them more adherent to phagocytic cells and more amenable to engulfment or ingestion. Some of opsonins are non-specific and can attack any type of pathogen, but the some opsonins are specific and bind to very specific antigen.

Agglutinins; as each antibody molecules has two identical binding sites, it can crosslink the pathogens by binding to an antigen on one pathogen in one binding site and the other binding site can bind to another antigen on another pathogen . When antibodies perform the crosslink of pathogens they agglutinate (clump together) pathogen, this inhibit the function of antigen and are readily engulfed by phagocytes.

Anti-toxin; pathogen cells are release molecules that may be toxins so some antibodies called anti-toxins will bind to the toxin molecules produced by the pathogen and renders them harmless.

Q6 (4.2,4.3)

1. Write a short explanation, which explain the difference between natural/acquired immunity and active/passive immunity
2. Immunity can be achieved naturally or artificially. Natural immunity is gained through normal life process. Artificial immunity is gained through medical intervention.  The immunity can also be achieved actively or passively. Actively immunity is gained when the immune system is activated and manufactures its own antibodies. Passively immunity is gained when the antibodies are supplied from another source.

3. Explain the basis of immunisation

According to world health organisation (WHO) Immunisation is the process whereby an individual is made immune or resistant to an infectious disease, this can be achieved by receiving vaccination usually in the form of an injection. Vaccines stimulate the body’s own immune system to protect the person against subsequent infection or disease and provide immunity to that disease. This is can be done by inject antigenic material; the antigenic material can be harmless or weakened pathogenic organisms or it can be a dead one, so immune system will treats the antigenic material as a real disease. As result the immune system is activated and manufactures the specific antibodies to that antigen and also the memory cells. The memory cells will provide the long term immunity so when the antigen of real disease the plasma cells will produce the correct antibodies to kill it. This known as the second immune response, which provides a quick immune response and a large number of antibodies to fight the antigen without showing any symptoms. There are two applications of vacation that provide immunity, the herd vaccination and the ring vaccination. The herd vaccination is using vaccine to provide immunity to all or almost all of the population at risk. So when enough people are immune, the disease can no longer spread through the population and herd immunity is achieved.  While the ring vaccination is used when a new case of disease is reported and involves vaccinating all the people in the immediate vicinity of new case.

Q7 (5.1)

Diabetes

Type:- metabolic disorder

Causes of disease:-