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1

 

A 4-year-old child is referred to you with the diagnosis of leukocyte adhesion defect. She has a history of recurrent bacterial infections, including pneumonias and skin abscesses. Radiography demonstrates granuloma-like lesions in her lungs and liver. However, the data in Table 1 suggests this condition has not been properly diagnosed. Which one of the following elements of these data is INCONSISTENT with a diagnosis of LAD?

CD2 values

CD19 values

CD18 values

CD4 values

CD3 values
            


 

CD 18 values - C. Correct. Leukocyte adhesion defect is an absence of LFA-1, CR3 and CR4. CD11a is a component of one of these receptors (LFA-1) and its expression is altered in these patients. CD11a pairs with CD18 to form the LFA-1 receptor. Because the actual defect in LAD is the absence of CD18, any receptor that uses CD18 would be absent from LAD cells. In this patient, the normal numbers of CD18-positive cells also indicate that she has been misdiagnosed.

2

A patient arrives at a clinic with a number of boils on his back, and a sample of pus from one of the lesions was sent to the laboratory for culture. The microbiology laboratory cultures heavy growth of Staphylococcus aureus, a gram-positive bacterium. Which of the following innate immune components is probably NOT involved in the protective response to this pathogen?

C5a

C3b

Superoxide

Lysozyme

TLR4

TLR 4 - LPS is not present in gram-positive bacteria.

3

The cartoon of the portly mouse below depicts the vascular and lymphatic systems, showing a T cell that will travel through both duct systems. Which of the following best represents the path taken by a naïve T cell?

Aorta, Heart, Lung, Lymphatic vessel, Gut, Lymph node, Aorta

Aorta, Spleen, Heart, Aorta, Lymph node, Lymphatic vessel, Heart, Lung, Aorta

The T cell is most likely to remain in the blood stream only, as there is no antigenic challenge.

Aorta, spleen OR lymph node; the T cell will remain at one of these secondary lymphoid structures until it encounters antigen.
            
 

Aorta, Spleen, Heart, Aorta, Lymph node, Lymphatic vessel, Heart, Lung, Aorta -  T cells travel through the blood stream to gain access to the secondary lymphoid structures, where they reside and ‘travel’ for a short time in search of antigen. If they do not encounter antigen (Question 4) within the lymphoid structure they exit via the draining veins (spleen) or efferent lymphatic ducts (lymph nodes), recirculate by making their way back to the heart where they begin their journey once again.

4

The neutrophils (N) in the accompanying photomicrograph are attracted to their extravascular location primarily by which one of the following factors?

C3a

C5a

C5b

Collagen

Fibrin

Neutrophil chemotactic factor
 
 

C5a - Neutrophils follow a gradient formed by complement factor C5a to the site of injury. Other factors may also be involved, including certain bacterial peptides, but C5a is the most widely known and understood

5

TAP is a component of which MHC pathway?

MHC class I pathway

6

Polymorphisms in HLA-A are most likely to influence the affinity of the interaction between which of the following pairs:

HLA-A and anchor residues

HLA and ß2m

HLA-A and CD8

HLA-A and chaperones

HLA and TAP
 

HLA-A and anchor residues - polymorphisms in HLA influence the ability of HLA to bind peptides and the TCR. The amino acids of the peptides that associate with HLA are called anchor residues.

7

You are characterizing the macrophage response to the bacterium Pseudomonas aeruoginosa. Knowing that this gram-negative bacterium has a potent endotoxin, you decide to determine if IL-1 transcription is activated by the pathogen through a Toll-like receptor. Which of the following signaling intermediates is involved in this pathway?

IκB

NFAT

NOD

PLCγ

Stat-1

 

IkB

8

Which one of the following is a “pattern recognition receptor” of the innate immune system that can distinguish host and microbial structures?

  • Fc receptor
  • Complement receptor 3 (CR3)
  • Toll-like receptor 9 (TLR9)
  • α-defensin
  • BCR

Toll-like receptor 9 - Correct. Toll-like receptors are good examples of receptors capable of recognizing molecular patterns on microbes and distinguishing them form host structures.

9

Which one of the following processes contributes most to the increase in affinity of an antibody response over time (affinity maturation), especially following multiple immunizations?

Somatic hypermutation

BCR editing

Ig class switching

Joining of V, D and J segments in memory B cells

Activation of Th1 cells
            

Somatic hypermutation -  Affinity maturation is the process by which an animal’s antibody response over time acquires a higher average affinity. This results from the selective activation of B cells that bear antigen receptors (BCR) with high affinity for the immunizing antigen. Somatic hypermutation occurs during memory B cell development and generates mutated BCR, some with much higher affinities for the antigen.

10

Recently, a patient was described who had a defect in TLR4-initiated cell signaling. Which of the following groups of microbes would be expected to cause recurrent infections in this patient?

Respiratory viruses

Fungi that cause vaginal yeast infections

Gram-negative bacteria

Gram-positive bacteria

Insect vector-borne parasites
            

Gram-negative bacteria - Toll-like receptor 4 (TLR4) is a member of receptors that recognize conserved microbial components and initiate innate immune responses. TLR4 is a specific signaling receptor for the lipopolysaccharides (LPS) found on gram-negative bacteria. It is not known to bind to fungal, viral or parasitic ligand.

11

Which one of the following properties would distinguish (be different between) IgG and IgM antibody molecules?

Their ability to activate complement

Their ability to bind to human mast cell Fc receptors

Their presence of κ light chains

Their ability to cross the placenta

Their ability to precipitate soluble antigens
            

Only human IgG can cross the placenta; IgM cannot.
 

12

Which one of the following properties of the complement system requires the terminal components, including C9?

Chemotaxis

Inflammation

Membrane attack (lysis)

Opsonization

Recognitition of microbes
 

Membrane attack - lysis

13

Which one of the following cytotoxic cells is most active against host cells that DO NOT express MHC class I molecules?

Cytotoxic T cells

Natural killer cells

Natural killer T cells

Neutrophil

Macrophage

NK cells bear an inhibitory receptor for MHC class I molecules that keeps the NK cells quiescent in the presence of class I molecules. In cells that lack class I expression (e.g., tumor cells or virus-infected cells), the inhibitory receptor is not engaged allowing the NK cell to become activated.

14

An immune-deficient patient is diagnosed with a congenital defect in RAG-2 expression. Which
of the following observations would MOST LIKELY be seen in this patient?

Aberrant B cell development in the thymus

A lack of peripheral B cells, T cells, and NK cells

An absence of double positive and single positive thymocytes

Normal peripheral B cell numbers and a lack of CD4+ T cells

Normal peripheral CD4+ T cell numbers and a lack of B cells

An absence of double positive and single positive thymocytes - RAG is required for the rearrangement of genes that encode the BCR and TCR.  Cells of the B and T cell lineages dependent on expression of a pre-BCR or pre-TCR would be absent or extremely low.  This includes any cell beyond the pre-B stage or the DN stage.

15

In which of the following infectious diseases is a Th1 pattern of cytokine production the most beneficial?

E. coli urinary tract infections

Tuberculosis

Streptococcal pneumonia

Pseudomonas-associated sepsis

Staphylococcal skin infections

Tuberculosis - Th1 cytokines, such as IFN-g, are important against intracellular bacterial pathogens, such as M. tuberculosis, the causative agent of tuberculosis. IFN-g serves to activate infected macrophages for bacteriocydal activity.

16

Mixed lymphocyte reaction does what?

C. The MLR is used to measure HLA incompatibility between two individuals.
 

17

Approximately how many Ig gene segments are required to produce antibodies with 1 billion different specificities?

1 billion

1 million

10

100 million

100

100

18

VLA-4 binds?

VCAM-1

19

The image below depicts a portion of the Peyer’s Patches of the small intestine. Match the following functions with the letters that appear in the photomicrograph. Note that for clarity, some duplicate structures are labeled with the same letters. The location of the cells responsible for initial antigen uptake is: 
 

D - villi

20

ABO blood antigens are:

Carbohydrates

21

Anaergy is a form of central or peripheral tolerance?

Both Central and Peripheral

22

What is the role of CR3?

The CR3 receptor binds Ag-Ab-iC3b complexes, and CR3 and CR4 are expressed on neutrophils and monocytes, 

23

The ligand for this cell surface receptor requires TAP for its expression. Which of the following is the cell surface receptor?

CD3

CD8

CD18

CD19

CD154

CD8 - CD8 binds to MHC class I molecules, which require the transporter of antigenic peptides (TAP) for their expression.

24

Which of the following processes contributes the most to the size of the repertoire of T cell antigen receptors of an individual?

DNA recombination

Large pools of V region genes

Somatic hypermutation

Polymorphism

Active immunization

DNA recombination - Recombination of the V, D, and J regions accounts leads to the production of 10^9 unique B and T cell clones.

25

At which one of the following stages of B cell differentiation does Bruton’s tyrosine kinase (Btk) first play an essential role?

Plasma cell

Memory B cell

Mature B cell

Immature B cell

Pre-B cell
 

Pre-B cell -  Precursor (Pre-) B cells are the first step in the B cell lineage that requires Btk for their maturation. This is evidence by deleting the gene in experimental animals or by studying XLA patients who lack a functional Btk. They do not show B cell lymphopoiesis beyond the pre-B cell stage.


 

26

An analysis of the blood lymphocyte subsets of an adult individual with a defect in his cell-mediated immunity was performed. Which one of the flow cytometry results shown in the figure below is consistent with a TAP deficiency in this patient? 
 

D - This is a normal pattern for blood lymphocytes, except for the absence of CD8+ T cells. With a TAP deficiency, the patient does not express MHC class I molecules and does not develop the CD8+ subset because of the lack of positive selection in the thymus.

27

Which of the following is a mechanism that regulates the size of the MHC class I repertoire within an individual:

Vd.J recombination

Each cell expresses two allelic forms of MHC class I

Forming dimers with different combinations of a and b genes

Somatic hypermutation of MHC class I genes

Different cell types express different allelic forms of MHC class I

Each cell expresses two allelic forms of MHC class I

28

Inducible Cox-2 activity functions in a pro-inflammatory pathway by? 

catalyzing prostanoid production in fibroblasts and macrophages

29

Which of the following is one of the most common causes of neutrophilia?

Parasitic infections

Chemotherapy for cancer

Bacterial infections

HIV/AIDS

Exposure to ionizing radiation

Bacterial infections - Elevated WBC counts should always suggest an infection.  Parasitic infections more often induce eosinophilia; chemotherapy generally produces neutrophenia; HIV results in lymphopenia; and radiation exposure can cause pancytopenia.

30

Cytotoxic T lymphocytes can use multiple mechanisms to kill target cells. These include:

Expression of Fas ligand and release of granzymes.

Detection of loss of MHCII from the cell surface.

Detection of loss of MHCI from the cell surface.

Production of reactive oxygen and nitrogen intermediates.

Generation of complement, and hydrolases that can attack and destroy cells.
 

Expression of Fas ligand and release of granzymes.

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