Makassar, 05 July 2021

TUTORIAL REPORT
MODULE 2 IMMUNOLOGY
SCENARIO I

Arranged by:
Group 1B

Fadila Ananda Putri. H 11020200137

Musdalifa 11020200142

Nadiyah Nurfadhilah 11020200150

Lucky Amelia Saad 11020200170

Muh. Dwi Cahyo Ramadhan 11020200173

Ollya Gaussyan khalillah Akbar 11020200181

Ashar Magguliling Tayibu 11020200199

Nurul Hikmah 11020200202

Ahmad Zaki Fauzan 11020200210

Putri Utami Haerunnisya 11020200220

Tutor: Dr. Dr. Hasta Handayani Idrus, M. Kes

MEDICAL FACULTY

INDONESIAN MUSLIM UNIVERSITY

MAKASSAR

2021
 INTRODUCTION
In the name of Allah SWT, the Most Gracious, the Most Merciful, we offer
praise and gratitude to Him, who has bestowed His grace, guidance, and inayah to
us, so that we can complete the Program Based Learning Report Module II
"Immunology" Scenario 1 this.

We have compiled this report to the maximum extent and the preparation of
this report would not have gone smoothly without the help of various parties,
therefore on this occasion we would like to thank:

1. Doctors who always provide advice and guidance during the discussion,
our supervisor, Dr. Dr. Hasta Handayani Idrus, M. kes for the guidance
given to us.
2. Literature sources used as references in our enrichment.

Despite all that, we are fully aware that there are still shortcomings both in
terms of sentence structure and grammar. Therefore, we welcome all suggestions
and criticisms from readers so that we can improve this report.

Finally, we hope that this Module II “Immunology” Scenario 1 Based Learning

Program Report can provide benefits to many people.

Makassar, 05 July 2021

Group 1B
 SCENARIO 1

A 32-year-old man comes to the clinic with a complaint of fever since 4 days ago.
Fever is felt mainly in the afternoon and evening, sometimes accompanied by
chills. The patient also complains of joint pain and fatigue. In addition, the patient
also complained of cough but no phlegm. Sometimes it's like flu and headache.
History 6 days ago the patient had just returned from Semarang, and had
undergone a swab antigen examination with a positive result. Vital sign
examination; body temperature 37.9o C, pulse 86 x / min and respiration 28 x /
min. Routine blood tests found a decreased leukocyte count.

I. DIFFICULT WORD
-Vital sign
-Antigen Swab
- Shivering

II. KEYWORD
-A 32 year old man with complaints of fever since 4 days ago
- Fever is felt mainly in the afternoon and evening, sometimes accompained by
chills.
- joint paint and fatigue
- Cough but to phlegm sometimes flu like and headache
- History 6 days ago the patient had just returned from semarang
- Had undergone a swab antigen examination with a positive result.
- Vital sign examination; body temperature 37.9o C, pulse 86 x / min and
respiration
28 x / min
- Routine blood tests found a decreased leukocyte count.

III. IMPORTANT QUESTION AND ANSWER

1. Explain the pathomechanism of fever and how does respond imun accour!
 The fever refers to an increase in body temperature due to infection or
inflammation. In response to microbial entry, certain phagocytic cells
(macrophages) secrete a chemical known as an endogenous pyrogen that
acts on the thermoregulatory center of the hypothalamus to raise the
thermostat setting

Fever here occurs through endogenous pyrogen mechanisms such as

PMN and non-PMN leukocytes as well as non – endogenous pyrogens,
drugs, and other foreign substances. Elevation of the hypothalamic set
point causes increased heat generation and reduced heat dissipation.
Clinically the patient is cold, chills, no sweating, cold extremities. To
reduce body temperature, it’s necessary to give antipyretics covered and
may be given chlorpromazine or an antihistamine. Pathogenesis through
exogenous pyrogens: toxins, infections, immune reactions, inflammatory
mediators will cause the migration of inflammatory cells which will
stimulate the release of endogenous pyrogens (IL-1, IL-6, TNF, IFN)
which further stimulates the hypothalamus to release PGE2 which will
increase c-AMP, so that the hypothalamic set point increases and fever
occurs. Posterior Hypothalamus as Heat Conservation Center and Anterior
Hypothalamus as Heat Loss Centre.

Temperatures in the febrile range increase the ability of antigen-

presenting cells to support the formation of the adaptive immune response.
Heat improves the phagocytic potential of macrophages and dendritic cells
(DCs) and increases their responsiveness to invading pathogens by
upregulating their expression of both Toll-like receptor 2 (TLR2) and
TLR4. Thermal treatment also induces the release of immunomodulatory
 molecules such as cytokines, nitric oxide and heat shock protein 70
(HSP70). Additionally, heat increases expression of MHC class I and II.
Dendritic cells (DCs) exposed to febrile temperatures are also more
efficient at cross-presenting antigens and inducing T helper 1 (Th1) cell
polarization.

2. Explain the classification of fever!

a. Septic fever

Body temperature gradually rises to very high levels at night and falls
back to above normal levels in the morning. Often accompanied by
complaints of chills and sweating. When If the high fever drops to a
normal level, it is also known as hectic fever.

b. Remittent fever

Body temperature can drop every day but never reaches normal body
temperature. The possible causes of temperature recorded can be as
high as two degrees and not as large as the temperature difference
noted for septic fever.

c. Intermittent fever

Body temperature drops to normal levels for several hours of the day.
If a fever like this occurs every two days it is called tersiana and if it
occurs two days free of fever between two attacks of fever it is called
quartana.

d. Continuous fever

Variations in temperature throughout the day do not differ by more

than one degree. A persistently high fever is called hyperpyrexia.

e. Cyclic fever

There is an increase in body temperature for several days followed by

several fever-free periods for several days which is then followed by
an increase in temperature as before.

3. What causes fever, especially in the afternoon and evening?

Body temperature normally fluctuates throughout the day, the lowest
temperature in the morning before waking (6 hours - 7 am) and the highest
in the afternoon and evening (5-6 pm). This variation is caused by
biological rhythms (biological clock). The master biological clock that
functions as a pacemaker for the body's circadian rhythm is the
suprachiasmatic nucleus (SCN). Body temperature is regulated by the
hypothalamus which regulates the balance between heat production and
heat loss. Heat production depends on metabolic activity and physical
activity. Heat loss occurs through radiation, evaporation, conduction and
convection.

Under normal circumstances the hypothalamus is always set at a set

point of about 37°C, after which information about temperature is
processed in the hypothalamus to determine the formation and heat contest
according to the set point. In the scenario there is an increase in night fever
because at that time the body's metabolism decreases so that the body
temperature drops. The body compensates by stimulating the posterior
hypothalamus which increases heat production. When the posterior
hypothalamus increases the production of body temperature, there will be
heat formation which is characterized by visits and skeletal muscle activity
in the form of objects.

Other causes of fever at night are:

1. External Pyrogens

Pyrogens (fever-inducing substances) that enter your body externally and

try to penetrate your body are one of the reasons that cause high fever only
at night. You will see that these pyrogens tend to produce toxins that can
be harmful to your health. Within the body, these pyrogens are produced
as a result of monocytes and macrophages. When external pyrogens enter
the body, they induce the body to produce its own pyrogens, thus resulting
in feverish conditions.

2. Upper Respiratory Tract Infections

Cold and other respiratory tract infections are probable causes of fever at
night. Sometimes, it is just a common cold that affects your body to cause
fever at night; other times, it can also be an infection of the larynx, bronchi
or the trachea that can cause major respiratory tract infections and, in
effect, causing fever that develops only at night.

3. Skin Infections

In many cases, fever at night is due to skin infections.

4. Connective Tissue Disorders

 In some cases, connective tissue disorders can cause fever at night. These
could include rheumatoid arthritis, giant cell arteritis, systemic lupus
erythematosus, polyarteritis nodosa, polymyositis, and dermatomyositis.

4. What is the mecanis of shivering and how does respond imun occur?
What physiologists explain about shivering is that when temperature-
sensitive nerve cells detect a drop in body temperature, they send signals
to the part of the brain that regulates body temperature. As a response, this
part of the brain activates neural pathways that eventually cause
involuntary muscle contractions to vibrate (shiver).

Shivering occurs when the temperature in the preoptic area of the

hypothalamus is lower than the body surface temperature. The efferent
shivering pathway originates from the posterior hypothalamus which
continues into the middle fore brain bundle. The increase in muscle tone
that occurs during the shivering process stems from neuronal changes that
occur in the areas of the mesencephalic reticular formation, dorsolateral
pons and medulla. Synchronization of motor movements that occur during
shivering is caused by intermittent inhibition of the Renshaw cells.

The motor center for shivering is located adjacent to the central area of
the posterior hypothalamus between impulses and incoming cold
receptors. This is normally inhibited by impulses from the heat-sensitive
preoptic area of the anterior hypothalamus, but when the impulse exceeds
this threshold, the motor center for shivering becomes activated, sending
impulses bilaterally to the anterior spinal cord motor neurons. Initially this
increases muscle tone throughout the body, but when muscle tone
increases above a certain level shivering occurs. The side effect of
shivering is that it reduces the immune response. Because shivering is an
immune response.

5. What causes the patients to complain of joint pain and fatigue?

Coronavirus disease 2019 (COVID-19) is a current global pandemic.
The case number has increased since December 31, 2019. It has been
reported that COVID-19 patients have been giving pain complaints, one of
which is muscular pain. Other types of pain that have also been reported
by COVID-19 patients are joint pain, stomach pain, and testicular pain.
Neuropathic pain is the rarest case among others. COVID-19 mechanisms
in the nerve and musculoskeletal damage are believed to be caused by the
expression and distribution of angiotensin-converting enzyme 2 (ACE-2).
 Joint pain (arthralgia) can occur in COVID-19 patients with a
prevalence of 10–15% . Joint pain (arthralgia) was also mentioned as one
of the possible early symptoms among COVID-19 patients.

The incidence of musculoskeletal pain is associated with increased

inflammatory responses. An increase in proinflammatory cytokines may
induce the formation of prostaglandin E2, which is a pain mediator with
its effect on peripheral pain receptors. A significant increase in pro-
inflammatory cytokines can cause cytokine storms. Cytokine storm is an
uncontrolled systemic inflammatory response resulting from the release of
large amounts of pro-inflammatory cytokines and chemokines by immune
effector cells in SARS-CoV-2.21 infection.

Based on current epidemiological investigations, the incubation period

for COVID-19 ranges from 1 to 14 days, and will generally occur within 3
to 7 days. Fever, fatigue and dry cough are considered as the main clinical
manifestations. Symptoms such as nasal congestion, runny nose,
pharyngalgia, myalgia and diarrhea are relatively rare in severe cases,
dyspnea and/or hypoxemia usually occur after one week after disease
onset, and worse can rapidly progress to acute respiratory distress
syndrome, septic shock. , metabolic acidosis is difficult to correct and
bleeding and coughing dysfunction and multiple organ failure, etc.
Patients with severe or critical illness may have moderate to low fever, or
no fever at all. Mild cases present only with slight fever, mild fatigue and
so on without any manifestation of pneumonia.

6. What is the pathomecanism of coughing and how does respon imun

occour?
The bronchi and trachea are very sensitive to light touch, so if there are
foreign objects or other irritants, even in very small amounts, they will
trigger a cough reflex. The larynx and carina (where the trachea branches
into the bronchi) are the most sensitive, and the terminal bronchioles and
even the alveoli are sensitive to corrosive chemical stimuli such as sulfur
dioxide or chlorine gas. Afferent impulses originating from the respiratory
tract mainly travel through the vagus nerve to the medulla of the brain.
There, an automatic sequence of events is set in motion by the neuronal
pathways of the medulla, causing the following effects: First.
approximately 2.5 liters of air is rapidly inspired. Second, the epiglottis
closes; and the vocal cords close tightly to trap air in the lungs. Third, the
abdominal muscles forcefully contract against the diaphragm, while other
expiratory muscles, such as the internal intercostals, also contract strongly.
As a result, the pressure in the lungs increases rapidly to 100 mm Hg or
more. Fourth, the vocal cords with the epiglottis suddenly open wide, so
that the high-pressure air in the lungs bursts out. Of course, this air is
sometimes expelled at a rate of 75-100 miles per hour. Importantly, it is
the strong compression of the lungs that causes the bronchi and trachea to
collapse through the invagination of the non-cartilaged part inward, as a
result of which the exploding air actually flows through the slits of the
bronchi and trachea. The rapidly flowing air usually carries any foreign
body that is in the bronchi or trachea.

In relation to the immune response, the innate immune response occurs

here. One of the cells that play a role in innate immunity is the surface
epithelium of the airways, which is very important in the body's defense
against invading enemies (pathogens).

There are a number of anatomical conditions and physiological

products of epithelial tissue as well as environmental conditions that
greatly determine the ongoing function of epithelial cells as a means of
defense, such as:

1. Mechanical defense
a. Rows of epithelial cells are tight (not loose) due to the strong inter-
epithelial binding, making the epithelial tissue difficult for
pathogens to pass through.
b. There is a flow of air and fluid that rinses the surface of the
epithelium.
c. The presence of mucus that wraps the microbes so that they are not
in direct contact with the airway epithelium By the movement of
the cilia on the epithelium of the airways, mucus/microbes will be
expelled.
2. Chemical defenses in the form of B-defensins and catelicidins present
in the respiratory tract.
7. What is the pathomecanism of flu and how does respon imun occour?
A number of airway droplets produce aerosols through evaporation and
the normal processes of breathing and speaking produce exhaled aerosols.
Therefore, a susceptible person can inhale the aerosol and can become
infected if the aerosol contains sufficient amounts of the virus to cause
infection in the person who inhales it. 

In the case of RNA viruses such as SARS CoV-2, this pathway is

initiated through the involvement of pattern recognition receptors by
single-stranded RNA and double-stranded RNA viruses via cytigolic RIG-
I like receptors and Toll like receptors in extracellular and endosomes.
Following PRR activation, the initial signaling cascade triggers cytokine
secretion. Among these, interferon type I/III is considered the most
important for antiviral defense, but other cytokines, such as the
proinflammatory tumor necrosis factor alpha, and interleukin-1 (IL-1), IL-
6, and IL-18 are also secreted. Together they induce an antiviral program
incells targetand potentially trigger an adaptive immune response. If the
response is early and well localized, IFN-I can effectively limit infection
CoV . 

8. How is the relationship between positive result on antigen swab

examination and the patient’s immune mechanism?
Rapid antigen test and antigen swab are the same type of test. It is
called a rapid antigen test, because the test to detect the corona virus can
provide fast diagnostic results, which is only in 15 minutes and the antigen
swab can detect the device becomes positive due to the presence of the
virus in the body.

Antigen test is an immune test that serves to detect the presence of

certain viral antigens that indicate the presence of a current viral infection.
Rapid antigen tests are commonly used to diagnose respiratory pathogens,
such as the influenza virus and respiratory syncytial virus (RSV).
However, the United States Food and Drug Administration (FDA) granted
an emergency use authorization (EUA) for antigen testing as a test to
identify SARS-CoV-2.

Antigens can be formed in the body because at the beginning of the

immune reaction process, the body's defense mechanism against any
foreign object that enters the body, a number of lymphocytes called
 memory cells immediately develop into lymphocytes which have the
ability to make long lasting immune substances. immunity). As mentioned
above, immunity is the mechanism of the human body to fight and destroy
foreign objects that enter the human body. These foreign bodies can be
bacteria, viruses, organ transplants, etc. When a cell or tissue such as
bacteria or an organ is transplanted into a person's body, that person's
body will reject it because the foreign object is not considered part of their
body tissue. The foreign object is considered as an invader who must be
expelled. So simply it can be redefined that the immune system is the
mechanism of the human body to fight / expel foreign objects that enter
their body. First of all "memory cells" seek to recognize foreign objects
that enter and are stored in the "memory" of these memory cells. This is
called the primary immune reaction. If the same foreign object enters the
person's body for the second time and so on, then these memory cells will
more quickly and very effectively stimulate the immune system to expel
and fight the known foreign object. The body's reaction will be faster and
more effective than the reaction when encountering a foreign object for
the first time.

9. What is the pathomecanism of shortness of breath and how does respond

imun occour?
Dyspnea is a sensation of running out of the air and of not being able to
breathe fast enough or deeply enough. It results from multiple interactions
of signals and receptors in the CNS, peripheral receptors chemoreceptors,
and mechanoreceptors in the upper airway, lungs, and chest wall.

The respiratory center of the brain is comprised of 3 neuron groupings

in the brain: the dorsal and ventral medullary groups and the pontine
grouping. The pontine grouping further classifies into the pneumotaxic
and apneustic centers. The dorsal medulla is responsible for inhalation; the
ventral medulla is responsible for exhalation; the pontine groupings are
responsible for modulating the intensity and frequency of the medullary
signals where the pneumotaxic groups limit inhalation and the apneustic
centers prolong and encourage inhalation. Each of these groups
communicates the another to work together for pacemaking potential of
respiration.

Mechanoreceptors located in the airways, trachea, lung, and pulmonary

vessels exist to provide sensory information to the respiratory center of the
brain regarding the volume of the lung space. There are 2 primary types of
thoracic sensors: slow adapting stretch spindles and rapid adapting irritant
receptors. Slow-acting spindle sensors convey only volume information.
However, the rapid-acting receptors respond to both volumes of the lung
information and chemical irritation triggers such as harmful foreign agents
that may be present. Both types of mechanoreceptors signal via cranial
nerve X (the vagus nerve) to the brain to increase the rate of breathing, the
volume of breathing, or to stimulate errant coughing patterns of breathing
secondary to irritants in the airway.

Peripheral chemoreceptors consist of the carotid and the aortic bodies.

Both sites function to monitor the partial pressure of arterial oxygen in the
blood. However, hypercapnia and acidosis increase the sensitivity of these
sensors, thus playing a partial role in the receptor’s function. The carotid
bodies are located at the bifurcation of the common carotid arteries, and
the aortic bodies are located within the aortic arch. Once stimulated by
hypoxia, they send a signal via cranial nerve IX (the glossopharyngeal
nerve) to the nucleus tractus solatarius in the brain which, in turn,
stimulates excitatory neurons to increase ventilation. It has been estimated
that the carotid bodies comprise of 15% the total driving force of
respiration.

Central chemoreceptors hold the majority of control over respiratory

drive. They function through sensing pH changes within the CNS. Primary
locations within the brain include the ventral surface of the medulla, and
the retrotrapezoid nucleus. The pH change within the brain and
surrounding cerebrospinal fluid is derived primarily by increases or
decreases in carbon dioxide levels. Carbon dioxide is a soluble lipid
molecule that freely diffuses across the blood-brain barrier. This
characteristic proves to be rather useful in that rapid changes in pH within
the cerebrospinal fluid are possible. Chemoreceptors responsive to pH
change are located on the ventral surface of the medulla. As these areas
become acidic, sensory input is generated to stimulate hyperventilation,
and carbon dioxide within the body is reduced through the increased
ventilation. When pH rises to more alkalotic levels, hypoventilation
occurs, and carbon dioxide levels decrease secondary to decreased
ventilation.

Respiratory centers located within the medulla oblongata and pons of

the brainstem are responsible for generating the baseline respiratory
rhythm. However, the rate of respiration is modified by allowing for
 aggregated sensory input from the peripheral sensory system which
monitors oxygenation, and the central sensory system which monitors pH,
and indirectly, carbon dioxide levels along with several other portions of
the cerebellar brain modulate to create a unified neural signal. The signal
is then sent to the primary muscles of respiration, the diaphragm, external
intercostals, and scalene muscles along with other minor muscles of
respiration.

10. What is the relationship between the decrease in leukocytes and the body
immune activity?
Based on scenario the patient has a swab antigen examination with a
positive result. As we know the swab antigen is device used to detect the
virus in the patient body. So, if the result of patient’s sweb antigen is
positive it’s mean the patient has a virus in his body.

If there is virus in patient body it allows infalammation. So, many

leukocytes leave blood capillaries by breaking through the endothelial
cells and penetrate into the tissue (deapedesis) to the affected area and can
cause leukocytes count in the blood circulation to decrease.

the migration of leukocytes into tissues

 Multistep leukocyte-endothelial interactions mediating leukocyte
recruitment into tissues. At sites of infection, macrophages that have
encountered microbes produce cytokines (such as TNF and IL-1) that
activate the endothelial cells of nearby venules to produce selectins,
ligands for integrins, and chemokines. Selectins mediate weak tethering of
blood leukocytes on the endothelium, and the shear force of blood flow
causes the leukocytes to roll along the endothelial surface. Chemokines
produced in the surrounding infected tissues or by the endothelial cells are
displayed on the endothelial surface and bind to receptors on the rolling
leukocytes, which results in activation of the leukocyte integrins to a high-
affinity binding state. The activated integrins bind to their Ig superfamily
ligands on the endothelial cells, and this mediates firm adhesion of
leukocytes. The leukocytes then crawl to junctions between endothelial
cells and migrate through the venular wall. Neutrophils, monocytes, and T
lymphocytes use essentially the same mechanisms to migrate out of the
blood.

11. What is the islamic perspective based on the scenario?

“ No muslim shall suffer from illness or other causes unless God wipes it
out with it (from pain) his ugliness (his sins) as the tree sheds its leaves.”
(HR imam muslim)
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