BIM ( P II) - Immunology tutorial 01

08.01.2024
Batch 32

01. Briefly describe the action of following cells in innate immune response.
a. Neutrophils
b. Eosinophils
c. Dendritic cells

a. Neutrophils are the most abundant type of white blood cells that circulate
in the blood and migrate to the site of infection. They are phagocytic cells
that engulf and destroy pathogens, especially bacteria and fungi. They also
release enzymes and reactive oxygen species that kill microbes and create
inflammation.
b. Eosinophils are granulocytes that contain granules filled with histamine,
major basic protein, and other substances. They are involved in allergic
reactions and parasitic infections. They can degranulate and release their
contents to damage the parasite’s membrane or coat it with antibodies to
facilitate its removal by other cells.
c. Dendritic cells are antigen-presenting cells that capture and process
antigens from pathogens or damaged cells. They migrate to the lymph nodes
and present the antigens to T cells, activating the adaptive immune response.
They also secrete cytokines that modulate the immune response.

02. What is the role humoral immunity in protecting neonates against

infections?
Humoral immunity is the part of the adaptive immune system that involves the
production of antibodies by B cells. Antibodies are proteins that bind to specific
antigens on the surface of pathogens and mark them for destruction by other
immune cells or complement proteins.

Humoral immunity plays an important role in protecting neonates against

infections, especially in the first few months of life when their own adaptive
immune system is still developing. Neonates receive passive humoral immunity
from their mothers through two main mechanisms:

Transplacental transfer: During pregnancy, maternal antibodies of the IgG class

cross the placenta and enter the fetal circulation. These antibodies provide
protection against various pathogens that the mother has encountered or been
vaccinated against, such as measles, rubella, tetanus, and hepatitis B.

Breast milk transfer: After birth, neonates receive maternal antibodies of the IgA
class through breast milk. These antibodies are secreted by the mammary glands
and coat the mucosal surfaces of the neonate’s gastrointestinal and respiratory
tracts. They prevent the attachment and invasion of pathogens, such as bacteria,
viruses, and parasites.

Since this largely antibody-mediated passive immunity can prevent the newborn
from infections, neonatal immunity depends strongly on the maternal concentration
of respective specific antibodies during pregnancy. If titers are low or wane rapidly
after birth, the protection transferred to the child may not be sufficient to prevent
disease.
03. How do antibodies prevent infections by ingested and inhaled microbes?

Antibodies are proteins that bind to specific antigens on the surface of pathogens
and mark them for destruction by other immune cells or complement proteins.
Antibodies prevent infections by ingested and inhaled microbes in different ways,
depending on their class and location:

IgA antibodies are found in saliva, tears, mucus, breast milk and intestinal fluid.
They protect against ingested and inhaled pathogens by preventing their
attachment and invasion of the mucosal surfaces of the gastrointestinal and
respiratory tracts.

IgG antibodies are the most abundant and versatile antibodies in the blood and
tissue fluids. They can neutralize toxins, block receptors, opsonize pathogens,
activate complement, and facilitate antibody-dependent cellular cytotoxicity
(ADCC).

IgE antibodies are mainly involved in allergic reactions and parasitic infections.
They bind to mast cells and basophils and trigger the release of histamine and other
inflammatory mediators when they encounter the antigen. This can cause
bronchoconstriction, mucus secretion, and increased vascular permeability, which
can help expel the pathogens from the airways or the gut.

IgM antibodies are the first antibodies to be produced in response to an infection.

They are pentameric molecules that can bind to multiple antigens and activate the
complement system, leading to the lysis of pathogens.

IgD antibodies are mainly found on the surface of B cells, where they may play a
role in B cell activation and differentiation.
04. Describe the mechanisms of immune deficiencies in the following
conditions;

a. HIV/AIDs
b. Corticosteroid therapy
c. Cytotoxic drugs
d. Malnutrition
e. Aging
f. Diabetes mellitus
g. Alcohol

a. HIV/AIDS: Human immunodeficiency virus (HIV) infects and destroys CD4+ T

cells, the main helper cells of the immune system. This leads to a progressive
decline in the number and function of CD4+ T cells, resulting in a loss of cell-
mediated immunity and increased susceptibility to opportunistic infections and
cancers. HIV also affects other immune cells, such as B cells, macrophages,
dendritic cells, and natural killer cells, impairing their ability to produce
antibodies, present antigens, and kill infected or abnormal cells.

b. Corticosteroid therapy: Corticosteroids are anti-inflammatory drugs that

suppress the immune system by inhibiting the production and release of cytokines,
the chemical messengers that regulate immune responses. Corticosteroids also
reduce the number and activity of lymphocytes, monocytes, eosinophils, and
basophils, affecting both innate and adaptive immunity. Corticosteroid therapy can
increase the risk of infections, especially by fungi, bacteria, and viruses, as well as
impair the healing of wounds and the response to vaccines.
.
c. Cytotoxic drugs: Cytotoxic drugs are agents that kill or inhibit the growth of
rapidly dividing cells, such as cancer cells. However, they also affect normal cells
that have a high turnover rate, such as bone marrow cells, which produce blood
cells. Cytotoxic drugs can cause bone marrow suppression, leading to reduced
levels of red blood cells (anemia), white blood cells (neutropenia), and platelets
(thrombocytopenia). This can compromise the oxygen delivery, the defense against
infections, and the clotting ability of the body. Cytotoxic drugs can also damage
the DNA of immune cells, causing mutations and impairing their function.

d. Malnutrition: Malnutrition is a condition that results from inadequate intake or

absorption of nutrients, such as proteins, vitamins, and minerals, that are essential
for the maintenance and regulation of the immune system. Malnutrition can affect
both innate and adaptive immunity by reducing the number and function of
immune cells, such as neutrophils, macrophages, natural killer cells, T cells, and B
cells. Malnutrition can also impair the production of cytokines, complement
proteins, and antibodies, as well as the integrity of the mucosal barriers that
prevent the entry of pathogens. Malnutrition can increase the susceptibility to
infections, especially by bacteria, viruses, and parasites, and reduce the response to
vaccines.

e. Aging: Aging is a natural process that involves the gradual deterioration of the
structure and function of various organs and tissues, including the immune system.
Aging can affect both innate and adaptive immunity by causing the decline in the
number and activity of immune cells, such as neutrophils, macrophages, natural
killer cells, T cells, and B cells. Aging can also reduce the diversity and specificity
of the antigen receptors on T cells and B cells, limiting their ability to recognize
and respond to new or mutated antigens. Aging can also alter the balance of
cytokines, favoring a pro-inflammatory state that can contribute to chronic diseases
and tissue damage. Aging can increase the vulnerability to infections, especially by
respiratory viruses, and reduce the response to vaccines.

f. Diabetes mellitus: Diabetes mellitus is a metabolic disorder that results from the
deficiency or resistance of insulin, a hormone that regulates the blood glucose
level. Diabetes mellitus can affect the immune system by causing hyperglycemia,
which can impair the function of immune cells, such as neutrophils, macrophages,
natural killer cells, T cells, and B cells. Hyperglycemia can also interfere with the
production of cytokines, complement proteins, and antibodies, as well as the
activation of the oxidative burst, a mechanism that kills microbes by producing
reactive oxygen species. Diabetes mellitus can also cause microvascular and
macrovascular complications, such as neuropathy, nephropathy, and
atherosclerosis, which can compromise the blood supply and the integrity of the
skin and mucous membranes, increasing the risk of infections, especially by
bacteria and fungi.

g. Alcohol: Alcohol is a psychoactive substance that can affect the central nervous
system and various organs and tissues, including the immune system. Alcohol can
affect both innate and adaptive immunity by altering the number and function of
immune cells, such as neutrophils, macrophages, natural killer cells, T cells, and B
cells. Alcohol can also modulate the production of cytokines, complement proteins,
and antibodies, as well as the expression of adhesion molecules and co-stimulatory
molecules, which are involved in the migration and activation of immune cells.
Alcohol can also impair the integrity of the mucosal barriers, especially in the
gastrointestinal and respiratory tracts, facilitating the translocation and colonization
of pathogens. Alcohol can increase the susceptibility to infections, especially by
bacteria, viruses, and fungi, and reduce the response to vaccines.

05. Discuss the possible infections in a patient with renal transplant and
how to prevent them?

A patient with renal transplant is at increased risk of infections due to the

immunosuppressive drugs that are required to prevent rejection of the transplanted
organ. These drugs reduce the ability of the immune system to fight off pathogens,
especially viruses, bacteria, and fungi. Some of the possible infections in a patient
with renal transplant are:

Cytomegalovirus (CMV): CMV is a common virus that can cause fever, fatigue,
pneumonia, colitis, hepatitis, and retinitis. CMV can be transmitted from the donor
organ, blood products, or close contact with infected individuals. CMV infection
can occur at any time after transplantation, but it is more common and severe in the
first six months. CMV infection can also increase the risk of rejection, graft loss,
and other opportunistic infections.

Bacterial infections: Bacterial infections can affect various sites, such as the
urinary tract, respiratory tract, skin, and wound. Bacterial infections can be caused
by common organisms, such as Escherichia coli, Staphylococcus aureus, and
Streptococcus pneumoniae, or by opportunistic organisms, such as Nocardia,
Listeria, and Mycobacterium. Bacterial infections can occur at any time after
transplantation, but they are more frequent and severe in the early post-transplant
period.

Fungal infections: Fungal infections can involve the lungs, sinuses, brain, skin, and
blood. Fungal infections can be caused by common fungi, such as Candida and
Aspergillus, or by opportunistic fungi, such as Cryptococcus, Histoplasma, and
Pneumocystis. Fungal infections can occur at any time after transplantation, but
they are more likely and serious in patients with high-dose immunosuppression,
prolonged antibiotic use, or prior exposure to endemic fungi.

To prevent these infections, a patient with renal transplant should follow these
general measures:
 Take the prescribed prophylactic medications, such as antiviral, antibacterial,
and antifungal agents, as directed by the transplant team. These medications
can reduce the risk of specific infections, such as CMV, Pneumocystis
pneumonia, and urinary tract infections.

Follow the recommended vaccination schedule, such as influenza,

pneumococcal, and hepatitis B vaccines, as advised by the transplant team.
These vaccines can protect against common infections, but they should be
given before or after the transplant, not during the period of intense
immunosuppression.

Avoid exposure to potential sources of infection, such as sick people,

animals, soil, and water. Practice good hygiene, such as washing hands,
cleaning wounds, and changing dressings. Wear a mask, gloves, and
protective clothing when necessary. Avoid raw or undercooked food,
unpasteurized dairy products, and tap water.

Monitor for signs and symptoms of infection, such as fever, chills, cough,
sore throat, pain, redness, swelling, or discharge. Report any changes or
concerns to the transplant team promptly. Seek medical attention if needed.
Do not self-medicate or stop taking the immunosuppressive drugs without
consulting the transplant team.
06. Define SIRS, Sepsis, severe sepsis and septic shock.

SIRS: Systemic inflammatory response syndrome (SIRS) is a set of criteria

that indicate a systemic inflammatory response to an infection or another
cause, such as trauma, burns, or pancreatitis. SIRS is defined by the presence
of at least two of the following: fever or hypothermia, tachycardia,
tachypnea, or leukocytosis.

Sepsis: Sepsis is SIRS plus a confirmed or suspected source of infection.

Sepsis can affect any organ system and cause various signs and symptoms,
such as altered mental status, hypotension, oliguria, or skin rash.

Severe sepsis: Severe sepsis is sepsis with organ dysfunction, hypoperfusion

abnormalities, or hypotension. Hypoperfusion abnormalities include lactic
 acidosis, oliguria, or acute alteration in mental status. Hypotension is defined
as a systolic blood pressure (SBP) less than 90 mm Hg or a drop of more than
40 mm Hg from baseline.

Septic shock: Septic shock is severe sepsis with persistent hypotension,

despite adequate fluid resuscitation, or a lactate level of at least 4 mmol/L.
Septic shock is a medical emergency that requires prompt recognition and
treatment, as it is associated with high mortality and morbidity.
07. Discuss is the role of cytokines in sepsis.

Cytokines are small proteins that act as messengers between cells of the immune
system. They regulate the inflammation, immunity, and tissue repair processes that
are involved in sepsis, a life-threatening condition that occurs when the body’s
response to an infection causes organ dysfunction or damage.
Cytokines can have both beneficial and harmful effects in sepsis, depending on
their type, amount, timing, and location. Some cytokines, such as tumor necrosis
factor (TNF), interleukin (IL)-1, and IL-6, are pro-inflammatory, meaning that they
stimulate the immune system to fight the infection and produce more cytokines.
However, excessive or prolonged production of these cytokines can cause a
“cytokine storm” that damages the body’s own tissues and organs, leading to
shock, multiple organ failure, and death.
Other cytokines, such as IL-10, transforming growth factor (TGF)-beta, and IL-4,
are anti-inflammatory, meaning that they suppress the immune system and limit the
inflammation. These cytokines can help to restore the balance and prevent
excessive tissue damage, but they can also impair the clearance of the infection and
increase the risk of secondary infections.
Therefore, the role of cytokines in sepsis is complex and dynamic, and it depends
on the balance between the pro-inflammatory and anti-inflammatory cytokines, as
well as the interaction with other factors, such as the type and load of the pathogen,
the genetic and environmental factors of the host, and the treatment interventions.

08. How do you diagnose a patient with sepsis and what is the initial
management?

Diagnosis
Identify the signs and symptoms of sepsis, such as fever, hypothermia, tachycardia,
tachypnea, hypotension, altered mental status, or oliguria. Use the quick Sequential
Organ Failure Assessment (qSOFA) score to assess the risk of mortality. A qSOFA
score of 2 or more indicates a high risk of poor outcome.
Perform a focused history and physical examination to identify the possible source
of infection, such as pneumonia, urinary tract infection, skin and soft tissue
infection, or intra-abdominal infection. Obtain blood cultures and other relevant
cultures before starting antibiotics, if possible.
Order laboratory tests to evaluate the organ function and the inflammatory
response, such as complete blood count, serum lactate, liver function tests, renal
function tests, and coagulation tests. A serum lactate level of 2 mmol/L or higher
indicates tissue hypoperfusion and a higher risk of mortality.
Order imaging studies as indicated by the clinical suspicion, such as chest X-ray,
ultrasound, computed tomography (CT) scan, or magnetic resonance imaging
(MRI) scan. These can help to confirm or exclude the source of infection and to
detect any complications, such as abscess, empyema, or necrosis.

Initial management
Start intravenous fluid resuscitation with crystalloid solutions, such as normal
saline or Ringer’s lactate, at a rate of 30 mL per kg of body weight. Monitor the
fluid responsiveness and the hemodynamic status of the patient. Avoid excessive
fluid administration, especially in patients with heart failure or acute respiratory
distress syndrome.
Start empiric antibiotic therapy with broad-spectrum agents that cover the most
likely pathogens, based on the source of infection and the local antimicrobial
resistance patterns. Adjust the antibiotic regimen according to the culture results
and the clinical response. De-escalate or discontinue the antibiotics as soon as
possible, based on the evidence of infection resolution.
Start vasopressor therapy with norepinephrine as the first-line agent, if the patient
remains hypotensive despite adequate fluid resuscitation, or if the serum lactate
level is 4 mmol/L or higher. Titrate the dose to achieve a mean arterial pressure of
at least 65 mm Hg. Add vasopressin or epinephrine as a second-line agent, if
needed. Avoid using dopamine, unless norepinephrine is not available.
Provide supplemental oxygen therapy to maintain a peripheral oxygen saturation of
at least 94%. Consider mechanical ventilation with low tidal volumes and positive
end-expiratory pressure, if the patient develops acute hypoxemic respiratory failure
or hypercapnic respiratory failure.
Measure the blood glucose level and start insulin therapy, if the blood glucose level
is higher than 180 mg/dL (10 mmol/L). Target a blood glucose level of 140 to 180
mg/dL (7.8 to 10 mmol/L). Avoid hypoglycemia, which can worsen the outcome of
sepsis.
Consider the use of corticosteroids, such as hydrocortisone, in patients with septic
shock who do not respond to fluid and vasopressor therapy. The optimal dose and
duration of corticosteroid therapy are uncertain, but a typical regimen is 200 mg
per day of hydrocortisone, given as a continuous infusion or in four divided doses,
for 3 to 7 days.
Consider the use of other adjunctive therapies, such as procalcitonin-guided
antibiotic stewardship, stress ulcer prophylaxis, venous thromboembolism
prophylaxis, and blood transfusion, based on the individual patient’s condition and
the local protocols.