Question1
- a) An appropriate type of immune cell for controlling intracellular infections.
Tuberculosis is a respiratory infection caused by a bacterium 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. (Shi et al., 2019, pg10) 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 simply 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. ( Bucşan et al., 2019, pg129) 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 long, and are most abundant in leukocytes. 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 lining of the effector T cell, which are responsible for immune responses by cell-mediated required by the host across the intracellular bacterial as well as viral pathogens. (Boonpiyathad, et al., 2020, pg90) Th1 cells also secrete IL-2, IL-10, TNF-alpha, and IFN-gamma. CD4+4 cells are also responsible for various functions such as activation of the immune system, cytotoxic T cells’ lymphocytes, non-immune cells, among others. 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 various immune cells such as T cells, macrophages, and neutrophils, which are responsible for the regulation of immune responses. Cytokines like IL2, TNF, and IFN-y play a crucial role during the infection.CD8 has the task of killing and destroying the Tuberculosis infected cells through granule mediated functions to increase apoptosis.CD8 can also generate granulysin that kills M.Tuberculosis (Carson et al., 2019, pg196).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, helping to eliminate tuberculosis infection (Hong et al., 2019, pg151). 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. ( Madhvi et al., 2019, pg69) Within these cells, Tuberculosis uses multiple mechanisms and modified phagosomes to invade both the adaptive and innate host immunity, including cytokine-mediated host defenses, resistance to innate microbicidal mechanisms, inhibition of phagosome maturation, and presentation.
To be effective, the T cell has to be activated by the communication from the affected macrophages to release necessary cytokines for activation of the antimicrobial capacity of macrophages and release the cells through a cytotoxic mechanism.CD8 plays a crucial role in killing 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 a contagious disease that affects all groups of people (Crakes et al., 2019, pg104). However, the infection level depends on the ability 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 (Kytikova et al., 2019, pg154). 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 (Lee et al.,2019, pg167). 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. It 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 extreme exposure to the causative agents (Mvungi et al., 2019, pg246). 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
Question2.
a). Lung pathophysiology of an asthma attack and symptoms
An asthma attack is a respiratory-related disorder that affects the respiratory tract. 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 (Olusola et al., 2020, pg12867. 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 Allergic Asthma, Adult-onset Asthma, Occupational Asthma, and Nonallergic 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. It responds to exposure to different stimuli that include irritants and allergens. Stimuli, such as cold air and vigorous exercise, can cause acute inflow obstruction.
Airway Adema.as asthma the condition becomes more persistent and inflammation more progressive, the limitation of airflow becomes more rampant (Ravan et al., 2019, pg127). The structural changes within the airways, including hypertrophy and hyperplasia, increase 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 respiratory hyperresponsiveness, including inflammation, structural changes, and dysfunctional neuroregulation. Inflammation determines the degree of hyperresponsiveness.
Airway remodeling. It refers to the permanent structural changes that occur in the breathing system and loss of lung function. It enhances structural cell activation that increases obstruction of airflow and air track responsiveness thereby, making the patient less responsive to therapy.
Asthma Attack symptoms.
Signs and symptoms of asthma attack vary from person to another, depending on the immune system and inflammatory response to the condition (Rodríguez et al., 2019, pg165). An asthma attack is mainly characterized by shortness of breath brought about by the narrowed airway, chest tightness and pain accompanied by difficulty in breathing. Other symptoms include trouble when sleeping due to shortness of breath, wheezing, and coughing, which is worsened by respiratory conditions such as cold and flu.
b). Immune sensitization process during an asthma attack.
The inflammatory responses in the respiratory tract of a person with asthma involve adaptive immunity and innate immune systems that drive and or initiate a chronic inflammatory response to stimuli (Roy et al., 2019, pg237). Both inflammatory and environmental stimuli trigger epithelium to produce mediators within the airway. Epithelium recruits and activates inflammatory cells that infiltrate the lungs and produce other mediators responsible for the augmentation of the immune responses within the epithelium, hence creating a chronic inflammation cycle.
The mediators involved in inflammation include cytokines, lymphokines, and proinflammatory cytokines, which are responsible for promoting and amplifying inflammatory responses, growth factors that promote cell survival, and chemokines chemoattractant for leukocytes and finally eicosanoids which are lipid mediators that have multiple effects in the respiratory system.
Inflammatory factors stimulate the respiratory epithelium to secrete thymic stromal lymphopoietin (TSLP), which recruits lung’s leukocytes and initiates dendritic cell functions in response to an allergy. Dendritic cells enhance differentiation of T cells into Th 17 and T-helper 2 cells. Th 17 and T-helper 2 cells induce immunoglobulin E(IgE) antibody from B cells through interleukin IL-13 and 4(IL-4) stimulation (Saglani and Custovic, 2019, pg200). Immunoglobin E combines to receptors on the surface of basophil and mast cells and also releases mediators that instigate bronchoconstriction that brings about the inflammatory response.
c). Challenges faced in diagnosing type 1 hypersensitivity and suitable medications.
Diagnosis of type 1 hypersensitivity involves a variety of diagnostic criteria for a bronchial asthma attack. The challenges associated with the diagnosis of type 1 hypersensitivity being, Misdiagnosis, is one of the significant challenges faced during type1 hypersensitivity. It is brought about by the similarities of asthma symptoms to other breathing conditions; symptoms include breathlessness, coughing, and wheezing, which are also common in chronic obstructive pulmonary diseases (Shi et al., 2019, pg102). 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 longer to be fully diagnosed.
Lack of standard diagnostic equipment, which leads o under-diagnosis, is also a recommendable challenge when carrying out a diagnosis to type 1 hypersensitivity. Modern equipment is so expensive and complicated, making it difficult to access and to operate. The available types of equipment tend to manipulate the result and lead to a delay in 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 (Sikazwe et al., 2019 pg67). 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 has also been recommended, preferable anaphylaxis or type 1 hypersensitivity reactions in ferrets.
Question 3.
a). Stages of HIV infection.
HIV infection occurs in three stages. The symptoms vary from one person to another, 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, causing severe damage to the immune system, exposing it to other opportunistic infections and related diseases. 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.
It 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 (Sinyor and Perez, 2019, pg123). There are no significant signs in this stage, with the only noticeable ones being upset stomach fever, rashes, joint ache, sore throat, swollen glands, joint and muscle pains. In this stage, the body reacts to HIV by producing HIV antibodies to attack the virus; this 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 cell count for CD4 T 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 ten to fifteen years, depending on the age and strength of the immune system of the infected person. However, the virus can still affect new cells and mutate within white blood cells and take shape (Stéphanie et al., 2019, pg114046). The virus can even be transmitted from one person to person. The suitable diagnosis is by measuring the Viral Load (HIV RNA). The test is used to determine the amount of virus present in the blood.
Stage 3. Symptomatic Stage.
The immune system is severely damaged and becomes weak during this stage. 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 chronic diarrhea, weight loss, severe pain, night sweats, persistent cough, and critical illness or diseases (Temesgen et al., 2019, pg1567). 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.
It is the final stage of HIV. At this point, the infected person has developed severe opportunistic infections due to the damage to the immune system. This is the final stage and can lead to death if left unattended.
b). Treatment approaches for HIV infection.
There Is no specific treatment for HIV/AIDs. However, the virus’s level can be reduced to an almost unnoticeable level and suppressed to become inactive. This fate has been achieved by the introduction and administering the Antiretroviral therapy to the infected persons.
The treatment of the virus also depends on the disease stage and the level of exposure to contaminated opportunistic infections. (Van Gasse et al., 2019, pg2229) The main aim of this treatment is to prevent the immune system from deteriorating to the extent of allowing the opportunistic infection to dominate. Administered 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.
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