BL222 Medical Microbiology

Exam 4: Chapters 16-19

This exam must be uploaded to Canvas as a Google Doc no later than Monday, November 6th
at 11:30 AM. Due to the generous time allotted for completion, any exam received after this
deadline is subject to a 50% grading penalty.

Please completely and directly answer the following questions as a work group. In class notes,
supplemental postings to Canvas, and your textbook are excellent resources to help get you
started, but you will need to perform outside research to provide quality answers for most of
these questions. Your outside sources must be:
Scholarly and credible; this includes other textbooks, journal articles, content from reputable
organizations (CDC, WHO, Pasteur Institute, etc.). Use of non-credible sources will be factored
in to your grade.
Properly cited via in-text citations and a formatted reference page (APA or Council of
Science Editors format preferred). No direct quotes are permitted in your answers; all material
should be appropriately paraphrased.

Please feel free to consult with me at any time if you have any questions about guidelines,
formatting, or clarification of material. Given the nature of this exam, I am unable to tell you
ahead of time if you have enough material to answer the question, if your answer is correct, etc.
I also strongly suggest that you develop a teamwork contract as soon as possible to help you
fairly divide the workload across your group (provided on next page).

Please note that plagiarism will not be tolerated in this assignment. Your answers will be
submitted to TurnItIn.com and evaluated for similarity to source material and to material
submitted by other students. Suspected instances of plagiarism will be reported to Academic
Affairs and will result in severe grading penalties and loss of groupwork privileges.

IMPORTANT NOTE ON GRADING: Demonstration of group effort and peer Team Member
Performance Evaluations will be taken into consideration for individual exam grades. In order to
track individual effort, each group must complete the Teamwork Contract on the next page and
perform all work within this Google Doc. In order to earn the privilege of the group exam score,
each student must 1) fulfill all obligations as listed on the Teamwork Contract and 2)
demonstrate a level of effort expected for students in a 200-level course. Failure to contribute
equally to the group effort will result in grading penalties.
Teamwork Contract (developed in part from Team Dynamics by Kolb and Francoeur)

Mission Statement:
Who is your point person to contact instructor, submit assignments, etc.?
Alexandra Barbera

When, where, and how will your team meet?

We will meet when all team members are available.
We will communicate through a group text message.
We will meet in an area accessible to everyone.
This area will be isolated and free of distractions.

Will there be a common agenda for meetings?

The group meeting are set up to allow us to come together and run ideas off of one
another. Our goal in these meetings is just to simply finish the group exam to the
best of our abilities. Our members believe that coming together helps us write and
efficiently answer questions.

What is expected of each member?

Each member is expected to participate and attend any scheduled meetings.
Each member expects respect out of one another.
Each member is expected to help other members that may be struggling with their
personal objective.

How will your team manage conflict?

We will talk out the conflict as a group and if the conflict cannot be resolved, we will
go to the instructor as a group to come to a conclusion.

List some key strengths/preferences of each member:

Alex- Very helpful when citing and finding applicable sources. Likes to talk things
over with other members to find the bigger picture. Is able to find connections
between sources very easily.
Hannah- A skilled writer and is a very good proofreader to fix and help other
members of the group with what they are trying to say. Helpful in keeping the group
on task and explaining what in depth articles are trying to say.
Victoria- Excellent in transferring ideas into complete thoughts and transferring
those thoughts onto paper. Very willing to help out other group members.
 Bryce- Great at interpreting scholarly articles and finding useful information. Very
good at piecing bits of information together to apply to different topics and ideas.
Good public speaker.

How will you ensure members are meeting their personal objectives?
We will ensure the members are meeting their personal objectives by meeting as a
group and discussing progress.
1. Answer the following questions regarding the adaptive immune system.

a. CASE STUDY. You are a physician assistant working in a primary care office. One of

your patients is a 10-year old boy who is in the office because his parents are concerned about

his recurring gastrointestinal and upper respiratory tract diseases. Over the last few years, the

child has suffered repeated bouts of diarrhea and various upper respiratory infections. After

youve confirmed that the child has received all childhood vaccinations with no reported side

effects, you are suspicious that the child may have some underlying cause for his repeated

bouts of illness. Both parents are healthy, and the boy is their only child. You do learn that the

boy has two uncles living in California who also have severe recurring bouts of sinus infections

and occasional gastrointestinal infections.

You suspect that your patient may have some underlying disorder of the immune system, so

you order some lab tests to determine the amount of IgG antibodies the boy has against

childhood vaccines and a complete blood cell count. Upon reviewing the lab test results, you

learn that the boy has normal IgG and IgM levels but no detectable levels of IgA. You consult

with the family, deciding that the best course of action is to treat the boys future infections as

they occur. You do not recommend that the boy undergo therapy to replace the missing IgA.

i. (2 pts) Why did you need to know if the boy received all of his childhood vaccines?

In active immunization, like the type of immunization given during childhood, the

body is injected with an inactive or dead antigen (1). The immune system uses these

pathogens to form antibodies and T cells that are specific to that antigen and keep

record of how to attach and destroy it (1). If the child had never received his vaccines,

his body would have had no way of making an antibody for the pathogens he is being

exposed to and would result in frequent infection.

ii. (2 pts) Why did you order the lab test to examine levels of IgG and IgM to childhood

vaccines?

IgM is the first antibody that is produced by the body in response to an infection

while IgG is produced after the fact to specifically target a certain antigen (2) . By a

clinician looking at the levels of IgG and IgM they are able to distinguish whether the

patient has previously had this type of infection in the past. This is able to be done

because high levels of IgM indicate that the infection is new because this is the bodys

general first response to new antigens, however if there are high levels of IgG this

indicates that the body has already had a run in with this disease because it is able to

activate its already formed memory B-cells to differentiate into antibody secreting

plasma B-cells creating a specific antigen response that would be IgG in this scenario

(1).

iii. (2 pts) What important information did you gather from learning that the two uncles have

similar disease symptoms?

The information pertaining to the two uncles having similar disease symptoms

allows the practitioner to lean towards the idea that this immune disorder was inherited

rather than developed during his lifetime. Primary immunodeficiencies have a genetic

basis and present in childhood (1). Because the patient is a child and has been

experiencing recurring infections, a primary immunodeficiency is suspected. An example

of a primary immunodeficiency is selective IgA deficiency with the primary infecting

pathogens being enteric bacteria and viruses (1). These pathogens usually infect the

gastrointestinal tract, nasal and eyes (1). The uncles presented with GI and sinus
 infections. The uncles symptoms correlate with that of selective IgA deficiency which can

be assumed that their condition is also that of a primary immunodeficiency. The fact that

the 10-year-old boy and the uncles have similar symptoms characteristic of primary

immunodeficiencies, specifically IgA deficiency, support the idea that the disease was

inherited on a genetic basis.

iv. (2 pts) How does the IgA deficiency correlate with the sites where infections are

occurring?

IgA is secreted onto mucous membranes to fight off pathogens that try to enter

the body (1). The upper respiratory and gastrointestinal tracts are two major portals of

entry to the body and are lined with mucous membranes, so a deficiency of IgA would

directly correlate with an inability for these parts of the body to fight off infection(1).

Additionally, bacteria with polysaccharide capsules can not be neutralized by the innate

immune system because they cannot be phagocytized (2). Therefore the only way to

fight off these kind of infections is for the bacteria to be targeted by either complement,

antibodies or antibiotics (1, 2).

v. (2 pts) Why would any attempt to replace the missing IgA antibodies be unsafe?

There have been correlations between B cell defects that affect maturation and

IgA deficiencies found in patients that have family members also suffering from IgA

deficiencies (3). IgA replacement therapy is unsafe because it can trigger anaphylaxis in

a patient that has IgG (3). IgG can act as an anti-IgA antibody that would attack the

foreign IgA. That is why this immunoglobulin replacement therapy is only considered for

patients that dont have IgG or IgE antibodies that would attack IgA (3).
b. (4 pts) IgM and IgG play major roles in the humoral immune response. Why do you

suppose a two antibody response system is used for the human immune system?

A two antibody response is used in the humoral immune system to help the body

buy time to elicit a proper response. The IgM antibody is the first immunoglobulin

produced by B-cells because it can be made without isotype switching allowing it to

bypass T-cell activation of B-cells (2) . This immunoglobulin type is a very generalized

antibody that has 10 antigen binding sites that look for certain pathogen factors such as

bacterial capsules and polysaccharides (2) . IgM is also helpful in the first response

because it is able to initiate the complement pathway starting the inflammation process

allowing the body to begin to control infections (2) . Overall this process buys the body

time to begin the process of isotype switching and this is where B-cells once activated by

the proper T-cell mass produce specific antibodies to rival the infection. In this case IgG

antibodies are being produced, which are the most abundant antibodies found in the

blood plasma (2) . IgG immunoglobulin, once produced, assists with inflammation and

opsonization of foreign microbes in body tissues. The IgG antibody is the more specific

antibody to that microbe while IgM is the more general response for the body.

c. (4 pts) Why do T cells need to bind to both antigen and to MHC receptors?

T cells only bind to antigens that are already present on the surface of another

cell, these cells are known as antigen-presenting cells (APCs). The surface proteins on

the APCs are called major histocompatibility complexes (MHCs). MHCs help to

distinguish between antigens that are created by the body and those that are foreign (1).

Another important structure that is vital to T cell binding are the T cell receptors (TCRs).
 These are distinctly different because they are antigen binding molecules that strictly

bind peptides and do not bind with a free-floating antigen (1). In order for TCRs to bind

to an antigen, the antigen must be attached to the MHC with an APC. It is necessary for

T cells to bind to both antigen and to MHC receptors to elicit an immune response.

Without T cell activation, the infection can spread and become devastating.

d. (5 pts) You are treating a patient who has AIDS. This patient has a low TH cell count.

Why does this patient have difficulty in making antibodies? How does this patient make any

antibodies at all? Do you recommend that this patient be vaccinated against influenza? Explain.

When treating a patient with AIDS it is important to understand that this individual

has well below normal levels of T-cells (below 200). T-cells are made in two initial

versions, CD4 and CD8, T-cells that display the antigen CD8 deal with cell mediated

immunity while T-cells that present the CD4 antigen work with antibody secreting

immunity (1). CD4 T-cells or helper T-cells come in five different versions making low

helper T-cells very important to an individual. The first type of helper T-cell, TH O, is the

base that can then be made into the other forms such as TH1, TH2, TH17, or regulatory

T-cells commonly known as Tregs (1). Each T-cell version is produced depending on the

type of immunity the body wants to use. When trying to figure out what version T-cell is

needed the body relies on cytokine production and depending on the type of cytokine

present tells the body what version of T-cell needs to be formed (1). If an AIDS patient

has a low number of helper T-cells they will have trouble being able to produce the

necessary versions of T-cells that stimulate B-cell activation and antibody production.

With this being known the patient is now vulnerable to microbes/viruses that normally

would not be a problem for a healthy individual and these microbes are known as
 opportunistic pathogens. Even though the helper T-cells levels are low, affecting their

ability to produce antibodies, they are still able to produce some antibodies because

there are still some left in the body. Since there are still some Helper T-cells that are able

to illicit a response it is advised that these patients are vaccinated against influenza. With

their immune system being in such a vulnerable state it is suggested that an inactivated

influenza virus is used. For certain patients who have severe versions HIV like AIDS it is

advised that before receiving the flu shot the patient undergoes p
re-exposure

chemoprophylaxis, which is a common antiviral drug that will help with regulating the spread

of the influenza virus (4). However, it is prohibited for immunocompromised patients to

receive the nasal-spray version of the flu vaccine because this vaccine does not use a dead

version of the disease but rather a weakened alive version that may still cause problems in

immunosuppressed patients (4). Immunocompromised patients should be given the flu shot

because it can help the bodys weakened immune system prepare for the influenza virus. If

an immunocompromised patient is not vaccinated ahead of time and they contract the

influenza virus they stand very little chance of fighting that virus off and it could possibly

become life threatening for that patient.

e. (4 pts) You are required to obtain a tuberculosis test in order to work at the hospital. You

opt for the traditional skin tuberculosis test.

i. Explain how this test works.

This test injects 0.1 mL of tuberculin purified protein derivative into the inner

forearm skin using a tuberculin syringe (5). The injection should initially produce a pale

raised area of the skin (5). The site is observed 48 hours to 72 hours later to determine if

there is a reaction (5). The purpose of the test is to determine the degree of
 hypersensitivity the body has towards the antigen (6). The bodys T cells that have

already been exposed and sensitized by prior infection of tuberculosis release

lymphokines to cause a local reaction after 24 hours at the site of injection (6). No

reaction after 48 hours concludes that the person does not have the disease, or not

enough time has passed for the body to react with the test (6).

ii. You complete the test, and unfortunately the test comes back positive. What does this

mean? Do you have an active TB infection? Explain.

A positive test can mean a variety of things, but one thing is known for sure:

additional tests need to be conducted. A red and peeling test site may be due to a type

IV hypersensitivity reaction due to antigen-specific T cells reacting with the BCG

vaccination for tuberculosis (1). The size and the type or reaction can also play a factor

in what the test result means. If the site of injection appears to have bubbles or tissue

necrosis, the patient is likely infected with tubercle bacilli (6). If the size of the reaction is

five millimeters, the person may have previously had and recovered from tuberculosis,

on immunosuppressants, or have been in recent contact of active tuberculosis (6). A test

that is ten millimeters of reaction is seen in people from high-risk countries, people

exposed to high-risk categories such as hospitals, or Mycobacteriology lab workers (6).

Fifteen millimeter reactions can be seen in any person including those with the BCG

vaccination or exposed to environmental mycobacteria (6). The person with a positive

test result may also have TB in the latent form and not an active tuberculosis infection

(6). The test may also display a false positive if the test was not administered correctly or

the patient had been infected with a mycobacterium species that did not cause
 tuberculosis (6). Additional tests, such as a chest x-ray, sputum analysis or blood test

should be performed to determine if it was a true positive result.

iii. Explain one other alternative immunological test for tuberculosis.

An alternative test that uses the patients immune system to diagnose

tuberculosis is in the form of a blood test. An Interferon Gamma Release Assay (IGRA)

is a blood test that measures how strong a patients immune system reacts to the

tuberculosis bacterium (7). There are two IGRA tests currently approved by the United

States Food and Drug Administration that are available. These tests are the

QuantiFERON-TB Gold In-Tube (QFT-GIT) test and T-SPOT.TB (T-Spot) test (7). In

these tests, blood is collected into special tubes and sent to the lab and analyzed (7).

IGRA tests are effective because infected patients white blood cells will release

interferon-g when mixed with M. tuberculosis antigens (8). The QFT-GIT test measures

the IFN-g concentration while the T-Spot test measures the number of IFN-g producing

cells (8). The tuberculosis antigens used in both tests are ESAT-6 and CFP-10, as well

as, TB7.7. in QFT-GIT tests (8). Positive results indicate that the patient has been

infected, but more tests would need to be conducted to determine whether he/she had

latent or active tuberculosis for the correct treatment plan (7). Negative results indicate

that neither a latent or active tuberculosis infection is likely (7). Advantages of IRGA tests

are that it only requires a single visit, results within 24 hours, and the BCG vaccination

does not cause a false positive like a skin test would (8). These tests do not determine if

the tuberculosis is latent or active and should not be taken in addition to the skin test (8).

iv. Which method would you recommend to your patients? Explain.

 The method recommended would differ on a patient to patient basis. If the patient

was a low risk patient, a skin test would be recommended. If a patient is at high risk for

infection a blood test may be recommended if their skin test came back negative (9). A

blood test would be recommended for those who received the BCG vaccine as a

false-positive reaction would occur in a skin test (9). Skin tests are recommended for

patients less than five years old (8). Another factor involves the availability of the tests

as well as their respective costs. If one test was more readily available or cost effective,

such as a skin test, that test would be recommended.

2. Answer the following questions regarding failures of the immune system.

a. (4 pts) Discuss the concept of immune tolerance. Why is this system necessary? What

are the consequences of a failure in tolerance?

Immune tolerance happens when T cells are essentially deleted from the

thymus when T cells react too strongly to an antigen (1). T cells first enter the thymus to

be separated by normal T cells or abnormal T cells. In positive selection, normal T cells

are allowed to live. This is due to the weak relationship between the TCRs and the MHC

(1). In negative selection, abnormal T cells are deleted. They are deleted because they

react too strongly to the MHC proteins (1). This system is necessary because if they

werent deleted, they would start to attack the MHC proteins regardless of the antigen

bound to it (1). When there is no self immune tolerance, the body will begin to attack

itself. When the body starts to attack its own self, it is called an autoimmune response

(1).
b. (5 pts) You are an obstetrician treating a female patient who is carrying a fetus that

developed hemolytic disease of the newborn. The patients blood type is A+, but she once

received a transfusion of AB+ blood while on a volunteer service trip abroad. The blood type of

the fetus is B+.

i. What is hemolytic disease of the newborn, and how does it develop?

Hemolytic disease of the newborn is a type II hypersensitivity that is also known

as Rh incompatibility disease (1). It develops when a mother that is Rh- becomes

pregnant and gives birth to an Rh+ baby (1). Similar to the way that you do not have an

allergic reaction the first time you are exposed to an allergen, the first Rh+ child that a

mother gives birth to will not experience incompatibility disease (1). Only the subsequent

Rh+ children will be in danger because when the first childs blood enters the mother's

blood during birth, the mothers immune system produces IgG antibodies and memory B

cells against Rh+ blood cells (1). It is these IgG antibodies that will be produced by

memory B cells, cross the placental barrier, and lyse the blood cells of the Rh+ babies

during the subsequent pregnancies (1).

ii. Fully explain why the fetus developed this condition even though another type B+ fetus

in a different type A+ mother was normal.

When the mother received a transfusion of AB+ blood, her immune system

recognized the B antigen as foreign (1). This recognition triggered the production of

anti-B IgG antibodies and memory B cells. The other mother has not been exposed to

any kind of type B blood cells before, so her immune system does not have the memory

B cells that are producing the IgG antibodies but rather just generic IgM anti-B

antibodies. In order for a fetus to develop this condition, the mothers blood would have
 had to have been exposed to the incompatible blood type before so that the mother

would have memory B cells ready to produce IgG antibodies upon a second exposure,

because IgG can cross the placenta(1). The other mother, who has not had a

transfusion, would also have anti-B antibodies but they would be mostly the IgM variety

that has an inability to cross the placental barrier.

iii. Why are the tissues of some people antigenic to others?

During development your T cells are being educated to not attack self cells, by

learning to recognize isogenic major histocompatibility complex proteins (MHC) (1).

Some of the T cells in your own body can recognize the MHC complexes on foreign cells

from a donor human (1). These allotypic MHC proteins appear to be a self cell that is

infected with a pathogen (1). This triggers Cytotoxic T cells to come and destroy the

tissues that are presenting these allotypic MHC proteins as if they were ridding the body

of a foreign antigenic/pathogenic body (1).

iv. What is the molecular basis for the four ABO and Rh blood groups?

The ABO blood group utilizes four carbohydrate antigens in which the sequence

of oligosaccharides on the red blood cell surface (10). The antigens are produced by the

ABO gene in three main allelic forms (10). These forms are A, B, AB, and O types that

arise from the H antigen precursor (10). The A and B antigens antigens arise because of

several single nucleotide polymorphism in the ABO gene resulting in a difference of 4

amino acids (10). The A transferase that makes the A antigen is the O allele of the ABO

gene codes for an inactive glycosyltransferase leaving the initial H antigen intact (10).

People that have Type B blood have the anti-A antibody in their blood and people with
 type A blood have the anti-B antibody(1). In the presence of an incompatible blood type,

the antibodies bind to the antigens on the incompatible red blood cells and destroy the

cell (1). This is the reason why people with type A and B blood cannot donate blood to

the other type (1). Type AB blood has neither antibody but both antigens so they can

only give blood to another AB+ blood type (1). Type O blood had both antibodies but

neither antigen so they are the universal donor but can only receive blood from other O-

(1).

v. How does a person become sensitized to the Rh factor? List consequences.

A person becomes sensitized to the Rh factor if they are Rh- and their blood

encounters Rh+ blood for the first time (10). This can happen during a blood transfusion

and cause hemolytic transfusion reaction (10). It can occur during pregnancy and cause

hemolytic disease of the newborn, particularly in a mothers second pregnancy since her

blood was exposed to the Rh factor during the first birth (1). Other than these two major

instances this exposure can occur any time Rh+ blood contaminates Rh- blood. The

pathophysiology of this exposure is that the Rh- blood is making anti-Rh factor

antibodies that attack and lyse the red blood cells containing the Rh protein and cause a

severe sickness in the blood reciever (10).

c. (4 pts) You are treating a patient who works at a mushroom farm. The patient suddenly

developed swollen lymph nodes, hives, and edema after several months of working at the farm.

i. What is your diagnosis for this patient? Fully explain the condition.

This patient has a type I hypersensitivity. The average time of a reaction onset is

2-30 minutes after exposure (1). This would explain the sudden onset of swollen lymph
 nodes, hives and edema. In his time working at the farm, he would have been exposed

to the antigen once before which would have sensitized him to the antigen by producing

antigen specific IgE antibodies, without causing symptoms (1). The second exposure to

the antigen is what would have actually caused the hives, edema and swollen lymph

nodes when coming in contact with IgE-coated mast cells (1). The severity of the

symptoms of a type I hypersensitivity depends on factors including the allergen, the

route of entry, and the number of sensitised mast cells present (1). The allergen, or

antigen, in this case is unknown, but may be a variety of things can cause a type I

hypersensitivity reaction. Allergy skin testing can be performed in order to determine the

allergen that the patient is reacting to.

ii. What mediators are responsible for these symptoms?

The antigen itself in the first mediator in the reaction process. The antigen comes

into contact with the second mediator, IgE, which coats mast cells (1). The mast cell

degranulates because cAMP levels are lowered, and releases histamine, prostaglandins,

leukotrienes, and chemotactic factors (1). The hives the patient is experiencing is due to

the increased release of histamines. Histamines bind to receptors on nerve cells to

cause itching, and loosen endothelial junctions of blood vessels to cause vasodilation

and permeability (1). The dilation and permeability of the blood vessels causes fluid

accumulation in the tissues resulting in raised welts, or hives (1). The leukotrienes and

prostaglandins also play a role in vasodilation and permeability (1). The combined effect

of these three mediators causing the permeability of blood vessels increasing fluid

accumulation in the tissues has the potential to cause edema in the patient (1). Swollen

lymph nodes occur during type I hypersensitivity due to the detection of an antigen. This
 causes the antibodies that bind to the antigen to begin to line along the walls of the

lymph vessels, which further causes the inflammation in the nodes (11).

iii. How would sensitivity to a particular antigen be determined?

The sensitivity to an antigen can be determined by performing an allergy skin test

(1). The skin test is an accurate and quick procedure that can be done in the clinical

setting (1). Extracts of the allergens are placed on the skin and then pricked to determine

if there is a reaction (1). The reaction results in a wheal, or a red and itchy bump on the

skin if there is a sensitivity to the antigen and if there is no reaction, there is no sensitivity

to that antigen (1).

iv. Other workers at the farm do not seem to be affected with these signs and symptoms.

What could explain this?

Other workers at the farm did not exhibit these signs and symptoms. This could

be caused by a variety of factors. One main factor is a difference in immune systems.

The other workers may not have a hypersensitivity to that particular antigen so even if

they were exposed, the antigen would have no effect on them. The exact reason of this

difference is not clear, but a genetic predisposition could be accountable (1). Other

reasons include the number of sensitized mast cells present and the allergen entry (1).

More sensitised mast cells would result in the symptoms appearing more severe. The

other workers may have the sensitivity, but if only a few mast cells are present and

undergo degranulation, the reaction might not be as severe enough to notice. The entry

of the allergen into the body can also determine how severe the reaction is (1). If the

allergen enters the bloodstream by injection or ingestion, more mast cells are able to be
triggered to degranulate as compared to only touching the skin in one area (1). If the

patient failed to wear protective gear, such as gloves, and had a small abrasion or the

allergen was inserted by something such as a needle prick or splinter, the allergen could

enter the bloodstream and cause a more widespread and severe reaction.
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