- a) An appropriate type of immune cell for controlling intracellular infections.
Tuberculosis is a respiratory infection caused by a bacteria known as mycobacteria Tuberculosis. The bacteria exist in small particles in free air, mostly in a dusty environment. The bacterium is taken up through inhalation through the upper respiratory tract and finally to the lungs. When the organism reaches the lung parenchyma, the bacteria invade and infect macrophages and dendritic cells within the lungs. Therefore, immunologists and health experts have gone a notch higher in the quest to find a long-lasting solution to Tuberculosis infection. Several immune cells have been examined to get the most appropriate and effective. The argument has been based on two primary immune cells; neutrophils and natural killer cells and also CD4+ TH1 and macrophages.
Neutrophils are innate immune cells directly involved in the process of an inflammatory response to the host’s tuberculosis infection. Neutrophils contribute to the generation of effector T cells involved in tissue necrosis, destruction, and infection dissemination and also participates in the formation of granuloma. On the other hand, killer cells protect the host from diseases by generating direct cytokine and antimicrobial cytotoxic factors, provide signals to regulate infiltration and increase activation of different immune cell numbers. Consequently, the extent and effectiveness of these cells depend on the host’s ability and inflammatory reactions towards protection and pathology. Neutrophils are short living and do not stay longer, at the same time, the most abundant leukocytes in the body. However, the ability of neutrophils to eliminate Tuberculosis has met several controversies.
CD4+ are compost of T helper type 1(Th1) cells, which form the lineage of the effector T cell, which are responsible for immune responses by cell-mediated required by the host against intracellular bacterial and viral pathogens. Th1 cells also secrete IFN-gamma, IL-2, IL-10, and TNF-alpha/beta.CD4+4 cells are also responsible for various functions, including activation of the innate immune system, cytotoxic T cells’ lymphocytes, non-immune cells, and even suppression of immune reaction in the body. Upon entry of Mycobacterium Tuberculosis in the body, Th1 responds immediately by secreting IFN-y and activating ant mycobacterial action in macrophages. To conclude, both neutrophils and CD4+ TH1 are essential requirements in response to eliminate Mycobacterium Tuberculosis in the body with CD4+ TH1 mentioned as the most effective and efficient.
b). The most effective cytokine for Mycobacterium Tuberculosis
Cytokines are a cell-signaling group of less molecular weight extracellular with components of glycoproteins and polypeptides synthesized by different immune cells mainly by T cells, macrophages, and neutrophils, which are responsible for the regulation of immune responses. Cytokines such as IL2, IFN-y, and TNF play a crucial role during the infection.CD8 has the task of killing and destroying the M.Tuberculosis infected cells through granule mediated functions to increase apoptosis.CD8 can also generate granulysin that kills M.Tuberculosis.Th17 cytokine has a role in protecting the body against Tuberculosis at the early stages to give time for the production of more monocytes and lymphocytes responsible for granuloma formation.
IFN-y cytokine produced by the T cell is also an essential factor in activating the macrophage. IFN-y also synergies with tumor necrosis factor during the macrophages’ activation, which helps in the elimination of tuberculosis infection. The cytokine also causes local tissue necrosis and systematic effects on fever and wasting caused by the release of TNF-alpha into the circulation. The body also produces anti-inflammatory cytokines such as TGF-beta, IL10, and IL4 in response to the entry of Mycobacterium Tuberculosis to help regulate the immune response and also limit tissue injury by inhibiting the extreme inflammatory response.
The excessive secretion of cytokines may result in malfunctioning hence failure to control infections causing disseminated Tuberculosis .in this case, increased production of IFN-y is required, and a reduced TNF-alpha.in conclusion, all the cytokines produced are all coordinated therefore are all crucial as well as important in the fight against mycobacterium tuberculosis. However, IFN-y cytokine proves to be more useful and practical since it performs multiple functions as compared to other cytokines. Therefore, the preferred choice Is IFN-y cytokine.
c). Antigen presentation process when macrophages are infected.
Mycobacterium tuberculosis can survive within the macrophages by inhibiting maturation phagolysosome. However, antigen presentation can still take place when the macrophages are infected. The bacterium infects phagocytic antigen-presenting cells (APC) in the lung, such as dendritic, lung macrophages, and alveolar macrophages. Within these cells, M.Tuberculosis uses multiple mechanisms and modified phagosomes to invade both the adaptive and innate host immunity, including resistance to innate microbicidal mechanisms, cytokine-mediated host defenses, inhibition of phagosome maturation and presentation.
To be effective, the T cell must be activated by the communication from the affected macrophages and release necessary cytokines to activate the antimicrobial capacity of macrophages or release the cells through a cytotoxic mechanism.CD8 plays a crucial role in killing M.tuberculosis infected cells through granule mediated mechanism or Fas-Fas ligand interaction to increase apoptosis.CD8 also generates granulysin that kills the organism directly.
CD4 T cells also activate effector functions in macrophages that help it to control the intracellular mycobacterium tuberculosis. The activation of macrophages helps stop the multiplication and replication of the intracellular bacteria through the antibacterial mechanism, including reactive nitrogen and oxygen intermediates.
D). The immune response of a healthy individual when exposed to mycobacterium Tuberculosis.
Tuberculosis is an infectious disease that can affect every group of people. However, the infection level depends on the ability of the inflammatory response and the strength of the immune system produced by the host exposed to the Mycobacterium Tuberculosis. Individuals who possess immune deficiency, such as those with HIV positive and the severely malnourished, experience severe consequences compared to healthy individuals.
Someone who is HIV positive has a weak immune system; Tuberculosis can multiply fast and cause destruction. The person infected with HIV positive or extremely malnourished is at least ten times more likely to get infected and develop active Tuberculosis than a healthy person, especially when their CD4 count is low, under 200.
A healthy person contains a strong immune system, with high white blood cell count, which counteracts the causative bacterial agents. Healthy individuals also have healthy tuberculin and cell-mediated immunity, which are relatively resistant to exogenous infections such as Tuberculosis. Tuberculin-positive in a healthy individual also responds fast to antigens responsible for Tuberculosis compared to tuberculin-negative, which is possessed by the unhealthy individuals.
E). Signs of being Immune-compromised.
Being immune-compromised is a state of having a weakened immune system responsible for the protection and fights against any infection. Considering the data provided above, patient immunity was relatively stable prior to the mycobacterium tuberculosis; therefore, he was not immune-compromised.
First, considering the patient’s occupation, that is, being a factory worker, the person was exposed to nearly all forms of the causative agents responsible for the transmission of Mycobacterium Tuberculosis. Factory emissions offer a suitable medium for the bacterial to be Transmitted.
Secondly, the person showed little or no noticeable signs and symptoms for the Tuberculosis prior to the diagnosis, with the only visible sign being ulcerating papule on his left arm. This indicates that the immune system responded positively to the bacteria before they were overwhelmed due to some other factors.
Thirdly, the patient had no past medical record despite his age and the extreme exposure to the causative agents. The patient was also examined, and the findings indicated relatively no sign of Tuberculosis. Other results like the temperature, platelet count, HIV status, malaria, white blood cell count, and pressure all showed a standard curve, with none of them showing a negative result. The findings, therefore, implicate a relatively good immune system. The patient also showed a negative sputum smear in the first test.
Upon confirmation of pulmonary Tuberculosis, the patient was started on TB therapy, where he responded well. The time he took to recover was appraised (10 weeks), indicating that the immune system responded well to the medications administered.
SELECTED QUESTIONS IN SECTION B ARE Q2 AND Q3.
Question 3.
a). Stages of HIV infection.
There are three stages of HIV infection. The symptoms vary from person to person depending on the type and severity of the Virus and the strength of the immune system and their response. The virus replicates within the body cause severe damage to the immune system exposing the body to other opportunistic diseases and related infections. The earlier the person is diagnosed with HIV and starts a proper medication, the better. The following are the three stages of HIV infection progress in the body if left unattended.
Stage 1. Acute primary infection or Window period.
This is the first stage of HIV in the body that occurs between the first contact of the infection and the detectable antibodies’ appearance to the Virus. The window period lasts for about three to four weeks. Currently, there has been approved as the most sensitive anti-HIV test that can be used during this period. There are no significant signs in this stage, with the only noticeable ones being, fever, rashes, sore throat, swollen glands, headache upset stomach, joint aches, and muscle pains. In this stage, the body reacts to HIV by producing HIV antibodies to attack the Virus; this process is known as seroconversion. The antigen/antibody test is used in the infection stage to determine the presence of viruses in the blood. These processes involve drawing blood from the vein; the antibodies are produced by the immune system when exposed to HIV.CD4 T cell count test can also be done at this stage to determine the CD4 T cell count in the blood.
Stage 2. The Asymptomatic stage.
This stage occurs immediately after the seroconversion process. In this stage, the Virus keeps multiplying in the blood, weakening the body’s immune system. The infected person tends to recover and assume a normal condition. The stage is not associated with numerous symptoms. The stage can last between 10 to 15 years, depending on the age and strength of the immune system of the infected person. However, the Virus will still affect new cells and mutate within white blood cells and take their shapes. The Virus can even be transmitted from one person to person. The suitable diagnosis is by measuring the Viral Load (HIV RNA). This test measures the amount of virus present in the blood.
Stage 3. Symptomatic Stage.
At this stage, the immune system is severely damaged, and the immune system is in the weakest point. The infected person is likely to suffer serious infections that would have been otherwise fought by the body system. These HIV related diseases are known as opportunistic infections. At this stage, the person is likely to experience symptoms like weight loss, chronic diarrhea, night sweats, severe fever, persistent cough, regular infections, and critical illness or diseases. Drug resistance method test is sometimes recommended to help determine if a specific virus has resistance to drugs. Other measuring methods like CD4 T and HIV RNA are also applicable to determine the presence and the level of Virus in the blood. The infected individual should be given serious treatment attention as fast as possible.
Stage.4 AIDs/ Full blown.
This the final stage of HIV. At this point, the infected person has developed severe opportunistic infections due to the virus’s damage to the immune system. This is the final stage and can lead to death if left unattended.
b). Treatment approaches for HIV treatment.
There Is no specific treatment for HIV/AIDs, however, the level of the Virus can be reduced to an almost unnoticeable level and suppressed to become inactive. This fate has Abeen achieved by the introduction and administering the Antiretroviral therapy to the infected persons.
The treatment of the Virus also depends on the stage of the disease and the level of exposure to contaminated opportunistic infections. The main aim of this treatment is to prevent the immune system from deteriorating to the extent of allowing the opportunistic infection to dominate. Administering of ART is recommended to anyone infected with HIV to reduce the viral load to an almost undetectable level.
Other current preventive measures include the introduction of both pre-exposure prophylaxis and post-exposure prophylaxis, especially to the more exposed groups such as nurses and the vulnerable groups like sex workers.
Question2.
a). Lung pathophysiology of an asthma attack and symptoms
Asthma is a respiratory-related disorder that affects the airways. When an individual is exposed to a trigger, the internal airways swell, this swelling narrows the space for air moving in and out of the lung. The muscles around the internal airways also tighten, making breathing harder, thus an asthma attack. Asthma is majorly caused by exposure to allergens or irritants like chemicals, cigarette smoke, mold, dust, and any other environmental factor.
Asthma is further divided into sub-groups, depending on the type of exposure and the causative agents. The groups include Adult-onset Asthma, Allergic Asthma, Nonallergic Asthma, and occupational Asthma.
Bronchoconstriction is the first pathophysiological process for an asthma attack; it involves the contraction of bronchial smooth muscle leading to the narrowing of the airways. I respond to exposure to various stimuli such as allergens and irritants. Other stimuli like cold air and vigorous exercise can also cause acute inflow obstruction. Stress may also play a role in precipitating Asthma exacerbation.
Airway Adema.as asthma the condition becomes more persistent and inflammation more progressive, the limitation of airflow becomes more rampant. The structural changes within the airways, including hypertrophy and hyperplasia, which increases with other factors like Adema, muscle hypersecretion, inflammation, and formation of inspissed mucus plug.
Airway hyperresponsiveness. This is the exaggerated bronchitis response to different varieties of stimuli. Various mechanisms are associated with airway hyperresponsiveness, which includes; dysfunctional neuroregulation, inflammation, and structural changes. The degree of hyperresponsiveness is much determined by inflammation.
Airway remodeling. This is the permanent structural changes that occur in the airway and loss of lung functional. Airway remodeling involves activation of structural cell that increases airflow obstruction and airways responsiveness making the patient less responsive to therapy.
Asthma symptoms.
Signs and symptoms of asthma attack vary from person to person depending on the immune system and inflammatory response to the condition. Asthma attack is mainly characterized with shortness of breath brought about by the narrowed airway. Chest tightness and pain accompanied with difficulty in breathing, trouble during sleeping caused by shortness of breath, coughing and wheezing which are worsened by respiratory conditions such as cold and flu.
b). Immune sensitization process during asthma attack.
the inflammatory responses in the respiratory track of a person with asthma involves, innate immune system and adaptive immunity that drives and initiates chronic inflammatory response to stimuli. Environmental and inflammatory stimuli initiate the production of mediators from the epithelium within the airway, epithelium recruits and activates inflammatory cells, inflammatory cells therefore infiltrate the lungs and release other mediators that are responsible for the augmentation of the inflammatory responses in the epithelium, hence creating a chronic inflammation cycle.
The mediators involved in inflammation include cytokines, lympokines, proinflammatory cytokines which are responsible in promoting and amplifying inflammatory responses, growth factors that promotes cell survival, chemokines that are chemoattractant for leukocytes and finally eicosanoids which are lipid mediators that have multiple effects in the respiratory system.
Inflammatory factors activate the respiratory epithelium to secrete thymic stromal lymphoproietin (TSLP) which recruits leukocytes to the lungs and initiates the function of dendritic cells in an allergic response. Dendrindic cells induces cell differentiation of T cells into T-helper 2 and Th17 cells. Both cells induce immunoglobulin E(IgE) antibody from B cells through interleukin 4(IL-4) and IL-13 stimulation. Immunoglobin E combines to receptors on the surface of basophil and mast cells and also releases mediators that induce bronchoconstriction and hence the inflammatory response is achieved.
c). Challenges faced in diagnosing type 1 hypersensitivity and suitable medications.
Diagnosis of type 1 hypersensitivity involves a variety diagnostic criteria for bronchial asthma attack. challenges associated with the diagnosis of type 1 hypersensitivity being, Misdiagnosis, this is one of the major challenge faced during type1 hypersensitivity, it I brought about by the similarities of symptoms of asthma to other breathing conditions, symptoms include, breathlessness, coughing and wheezing which are also common in chronic obstructive pulmonary diseases. Therefore, the condition can be misunderstood. The same case can also be experienced in children since they display similar symptoms to cold or viral bronchitis which are also associated with wheezing and coughing. The result tends to take long to be fully diagnosed.
Lack of standard diagnostic equipment which leads o under diagnosis is also a recommendable challenge when carrying out diagnosis to type 1 hypersensitivity. The modern equipment’s are so expensive and complicated making it difficult to access and to operate. The available equipment’s tend to manipulate the result and also lead to delay of the diagnosis.
Suitable medications to type 1 hypersensitivity.
Hypersensitivity reactions can be prevented by offering pretreatment with histamine-1 (H 1) and H2 receptor antagonists to the patient. In the most critical cases, therapy should consist of instituting fluid therapy, discontinuing the drug, and administering an H 1 receptor blocker such as diphenhydramine and glucocorticoids which are as well dexamethasone. Epinephrine can be administered in severe and refractory cases. Vaccination have been also recommended preferable anaphylaxis or type 1 hypersensitivity reactions in ferrets.