Clinical Microbiology HW#7

Concept Map: Antibodies

1. Phagocytosis is a process for engulfing large particles (>1μm). Which feature of antibodies will help to make particles larger, therefore enhancing phagocytosis?

Agglutination

2. The flu virus mutates fairly frequently. Its adhesive proteins change such that we have different "strains" of influenza each year. When a particular flu virus mutates such that its adhesive proteins change, which function of antibodies is disrupted?

Neutralization

3. __________________ stimulated with ___________ differentiate into __________, which secrete antibodies into the bloodstream.

B-cells, antigen, plasma cells

Microbiology Animation: Humoral Immunity: Clonal Selection and Expansion

1. Which of the following best characterizes clonal selection?

The production of identical B cells producing the same antibody.

2. What is produced by the process of clonal expansion?

Plasma cells and memory B cells

3. An antigen that is potent enough to activate a B cell on its own is known as

T-independent antigens

4. Based on the animation, T cells recognized the antigen displayed by what protein of the B cell?

MHC

5. How can a sufficient humoral immune response occur if a plasma cell only lives for a few days?

Each plasma cell can produce up to 2000 antibodies every second

Chapter 17 Reading Questions

1. What is the correct sequence of events for activation of a B cell by a T-dependent antigen?

(1) Immunoglobulin receptors on the B cell recognize and bind the antigen. (2) An antigen fragment in complex with MHC class 2 is displayed on the B cell's surface. (3) The MHC-antigen complex binds a receptor on a T_H cell. (4) The T_H cell secretes cytokines that activate the B cell.

2. An individual may be exposed to a pathogen and become infected without actually getting sick. This is known as a subclinical infection. Even in subclinical infections, the individual's adaptive immune system can generate memory for the pathogen. What type of adaptive immunity is this?

Naturally acquired active immunity

3. If a patient has been exposed to an antigen for the first time, which class of immunoglobulin appears first?

IgM

4. Which of the following statements concerning immunological memory is true?

The memory response is due to production of long-lived cells that can very rapidly upon second exposure.

FALSE:

The memory response is usually faster but not as strong.

Antibodies produced in response to a secondary infection are mostly IgM.

The memory response involves only B cells.

Chapter 17

1. What type of immunity results from vaccination?

Artificially acquired active immunity

2. What type of immunity results from transfer of antibodies from one individual to a susceptible individual by means of injection?

Artificially acquired passive immunity

3. Which of the following is the best definition of epitope?

Specific regions on antigens that interact with antibodies

4. Which of the following statements is NOT a possible outcome of antigen-antibody reaction?

Clonal deletion

5. The specificity of an antibody is due to

The variable portions of the H and L chains

6. The antibodies found in mucus, saliva, and tears are

IgA

7. Which of the following statements is FALSE?

The constant region of a heavy chain is the same for all antibodies.

TRUE:

The variable region of a light chain binds with antigen.

The variable region of a heavy chain binds with antigen.

The Fc region attaches to a host cell.

8. In the figure, which areas represent antigen-binding sites?

 

A and B. The parallel diagonal lines on the left.

9. Cytokines are protein-based chemical messengers that allow for communication between cells of the immune system.

TRUE

10. Cytokine storms negatively impact human health.

TRUE

11. The production of interferons at an infection site is critical for chemotaxis.

FALSE

12. The implementation of vaccinations occurred prior to experimental support for the germ theory of disease.

TRUE

13. In the figure, which areas are similar for all IgG antibodies?

 

C and D. The parallel vertical lines.

 

The Wiggly Little Boy

A few months ago Dr. Trapper’s, 4-year-old son, Caleb, woke him up at 3:00 am, complaining that he didn’t feel good. Caleb said his head and ears hurt, and he and his bed were “all wiggly.” He had a runny nose the past few days, but the Trappers had thought nothing of it. Dr. Trapper took Caleb into the bathroom and noticed he looked flushed and his glands appeared swollen compared to normal.

Dr. Trapper gave Caleb a hug and he felt very hot. A quick check with the thermometer demonstrated he was running a fever of 101.8°F. Caleb didn’t show any other obvious symptoms. While somewhat concerned, Dr. Trapper was not overly worried as Caleb had been a very healthy child and received all his vaccinations.

1. Which of the following is the most likely possible diagnosis for Caleb?

Ear infection

**Hopefully, you recognized the signs and symptoms of an “ear infection” (otitis media, OM): pain and pressure in the ears or head, fever, and feeling “wiggly,” which we later deduced to be a 4-yr-old’s way of describing the imbalance and dizziness he felt from his inner ear dysfunction! OM is responsible for millions of pediatric infections per year.

2. While we usually think of fever as a bad thing, a fever is actually signifying that an immune response is progressing! Overall, which of the following cytokines would be most involved in increasing Caleb’s fever response?

Interleukin 1

**When immune cells sense pathogens, certain components of the pathogen stimulate the innate cells to produce cytokines. When Interleukin-1 is produced, it acts on the hypothalamus to “crank up the heat” and results in fever and increased inflammatory processes. The other cytokines listed have separate functions such as T-cell responses (Interleukin-2), B-cell responses (Interleukin -4), anti-inflammation (Interleukin -10), or cell differentiation (Interleukin -12).

3. When morning came, Caleb had not improved, so the Trappers took him to the pediatrician. A quick examination with the otoscope revealed a Bulging eardrum. The examination led to a diagnosis of otitis media (OM), or an ear infection. The picture on the left demonstrates a swollen, red eardrum with a fluid buildup behind the membrane. The immune processes most involved in the inflammation seen behind Caleb’s eardrum would be attributed to:

Vasodilation of capillaries and accumulation of immune cells, fluid or pus

**The acute inflammatory processes provide noticeable signs, symptoms, and clinical clues such as pain, heat, and swelling to show that the body is attempting to fight the pathogen. This manifests when vasodilation increases blood flow to the area and produces erythema and edema. Specifically, edema is the result of the increased permeability of post-capillary venules as signaled by inflammatory cytokines and allows immune cells and microbe-fighting proteins to arrive at the area.

4. Most patients would happily accept a prescription for antibiotics from the pediatrician and go home. But as a microbiologist, Dr. Trapper wanted to identify the infectious etiology and see what was going on inside his son. Even though it’s not standard procedure for otitis media, he asked for some of the fluid contained behind the eardrum to be collected with a syringe (tympanocentesis) so he could analyze it for culture and sensitivity in his lab. He stained the fluid and examined it under the microscopic field. Interestingly, although he did not find any noticeable bacterial organisms, he did find high numbers of this characteristic responding cell type (picture), which could likely be identified as a:

Neutrophil

**The appearance of the nucleus and cytoplasm of these cells would identify them as neutrophils (a.k.a. “polymorphonuclear leukocytes” or PMNs). They are part of the innate class of cells known as “granulocytes” which comprise a large percentage of responding innate cells. Increasing numbers of neutrophils, known as leukocytosis or “raised white blood cell counts” are often clinically important for diagnosis of acute bacterial infection, especially pyogenic infection. Often, these can be seen on common hospital lab reports as “bands” or “shifts”. These terms refer to immature neutrophils that are released from reserves in the bone marrow because they are needed to battle invading bacteria. Because they have not had enough time to ‘grow up’ they can be distinguished by phenotype and quantified. Neutrophils are some of the “first responder cells” that migrate the area of infection and their death results in the production of pus as noted in our patient, Caleb.

5. Dr. Trapper wasn’t going to give up easily and continued to scan the overall field for bacterial clues, but all he found were more immune cells. Soon, he noticed something else interesting…several cells were interacting! The likely identities of these cells based on morphologies could be best described as:

Adaptive immune cell and an antigen presenting cell

**This interaction represents a critical turn in the immune response. The cell on the right (grey) is likely a lymphocyte, a component of the adaptive lines of defense. The cell on the left (purple) is an innate cell, likely a dendritic cell. This is probably representative of the interaction of an antigen-presenting cell (APC). The result of antigen presentation is to activate and bring powerful adaptive cells like B cells and T cells into the fight and provides tertiary immune responses such as antibody production (B cells), cytotoxicity (CD8 T cells), or ‘helper/coordination’ (CD4 T cells) functions. Without this APC interaction, the third line of defense would be inactive in our plight against antigen and our overall responses would suffer. Most other choices can be ruled out due to the phenotypic appearances.

6. Caleb recovered without incident, but because there are millions of cases of ear infections every year in the U.S., Dr. Trapper wanted to make sure that this would not be the first of many recurrent ear infections for his son. He wanted to ensure that Caleb did not have an underlying immunodeficiency that would cause his future responses to fight antigens suboptimally. He asked the physician to do a serology analysis of Caleb, which consisted of probing for each antibody isotype found and to report how much is present. The analysis yielded the following results. What might you conclude from this?

Probe	Qualitative Result
Anti-whole human antiserum	+++
Anti-IgG	++
Anti-IgA	++
Anti-IgM	+

Caleb has a normal response.

**Caleb’s antibody response is perfect and producing as predicted! As the immune response progresses, we hope our responses become specialized to best combat the antigen. This includes adaptive immune activation and eventual memory responses. When we have T cell help (from CD4+ T cells) and plasma B cell responses, we fine-tune the response to make more productive antibody types. These changes produce better-qualified antibodies to bind the antigen via clonal selection and immunoglobulin class switching. Caleb’s data shows he is producing large amounts of the efficient antibody, IgG, instead of the inefficient “rookie” antibody IgM.

7. If this particular antigen attempts to re-infect Caleb, it’s in for a bigger fight. By getting activation of adaptive immune cells such as B-cells and T-cells, the body generates an extra layer of protection. What is a critical advantage for Caleb the next time he encounters this antigen?

Anamnestic (memory) responses and future vaccinations to augment the response

**The major difference between innate responses and adaptive responses is the formation of memory cells Innate cells respond the same way each time. They search for simple antigenic patterns (pathogen-associated molecular patterns or PAMPs) and act on those patterns, and one cell can detect and respond to multiple antigens. Adaptive cells are specific for a single molecular pattern and tend to act even more effectively each time they encounter it.