Cells and Signals of the Immune System

Question 1

Adaptive Immunity is composed of two responses. What cells mediate each response?

Answer 1

1. Humoral immunity is mediated by B lymphocytes

2. Cell-mediated immunity is mediated by T lymphocytes (also macrophages, NK cells)

Question 2

B and T cell proliferation in early lymphocte maturation is stimulated by which cytokine?

Answer 2

IL-7

Question 3

What interacts with the T-cell receptor (TCR) of an immature, double positive T cell (CD4+/CD8+ to signal differentiation into a single positive cell? In what organ does this occur?

Answer 3

Interaction with either major histocompatibility complex I (MHC I) (CD8+) or MHC II (CD4+) in the coretex of the thymus

Question 4

What two processes eliminate immature T cells lacking proper antigen receptor specificities?

Answer 4

1. Positive selection selects for lymphocytes with TCRs that recognize self-MHC proteins, ensuring that only T cells with TCR that recognize MHC mature.
2. Negative selection eliminates autoreactive T cells that bind to MHC with high affinity.

Question 5

What mechanism drives cell elimination in positive selection?

Answer 5

T cells that cannot bind to self-MHC molecules undergo apoptosis

Question 6

Apoptosis of T-helper cells (CD4+, Th) or cytotoxic T cells (CD8+, Tc) bearing TCRs for self-proteins is the result of what process?

Answer 6

Tolerance, which prevents autoimmune reactions

Question 7

What cytokine released by activated Th further stimulates Th-cell survival/proliferation?

Answer 7

IL-2. It binds to the IL-2receptor on Th cells causing further proliferation

Question 8

Name the two signals that are needed to activate T cells:

Answer 8

1. The first signal is the MHC/antigen complex interaction with a TCR specific for that antigen
2. The second is the costimulatory signal of the CD28 protein on the T cell with the B7 protein on the antigen presenting cells (APC)

Question 9

What is the result of an interaction between a T cell and an APC in the absence of costimulation?

Answer 9

Anergy or unresponsiveness of T cells

Question 10

What T-cell protein displaces CD28 from B7, inhibiting T-cell activation and ensuring T cell homeostasis?

Answer 10

Cytotoxic T lymphocyte antigen 4 (CTLA-4)

Question 11

Which MHC class molecule presents processed antigens from organisms that have been phagocytosed? What cells possess this MHC class?

Answer 11

MHC-II complexes on professional APC present extracellular, phagocytosed proteins to Th cells

Question 12

What cells function as professional APCs?

Answer 12

Dendritic cells, macrophages, and B cells

Question 13

What is the source of antigen presented by MHC-I molecules? What cells possess this class?

Answer 13

MHC-I complexes on ALL nucleated cells present intracellular proteins proteins to Tc cells

Question 14

What is the cluster of polypeptides present in all T cells that is important in signal transduction by the TCR?

Answer 14

CD3 complex

Question 15

Induction of which of the T-cell helper lines (Th1 or Th2) elicits a more effective response against intracellular pathogens such as Mycobacterium tuberculosis?

Answer 15

Th1 cells are more effective against intracellular pathogens

Question 16

Which cytokine released by Th1 cells is involved in macrophage activation?

Answer 16

gamma-Interferon (y-INF)

Question 17

What other signaling pathway results in macrophage activation?

Answer 17

The interaction of CD40 on macrophages with CD40L on T cells

Question 18

What transcription factor is involved in both INF-y and CD40/CD40L signaling?

Answer 18

Nuclear factor-kB

Question 19

How do macrophages respond to y-INF and CD40/CD40L signaling?

Answer 19

Cytokine release, increased microbicidal activity, increased phagocytic activity (through upregulation of B7and MHC II)

Question 20

Once activated, what are the major cytokines released by macrophages?

Answer 20

Tumor necrosis factor (TNF)
IL-1
IL-8 (leukocyte recruitment)
IL-6 (lymphocyte activation
IL-12 (Th1 differentiation)

Question 21

What are the microbicidal substances produced by activated macrophages?

Answer 21

Reactive oxygen species, nitric oxide, and lysosomal enzymes

Question 22

What are the main effector cells and cytokines of delayed hypersensitivity?

Answer 22

Macrophages induce differentiation of naive Th cells into Th1 cells by secretion of IL-12. IL-12 acts on NK cells to produce y-INF which also promotes Th1 differentiation. Th1 cells in turn release y-INF, activating macrophages

Question 23

Against what pathogens is delayed hypersensitivity needed?

Answer 23

Intracellular pathogens (eg. M tuberculosis, Salmonella typhimurium, and Histoplasma)

Question 24

Patients with T-cell deficiencies are most susceptible to what families of pathogens?

Answer 24

All severe T-cell deficiencies leave patients particularly susceptible to mycobacterial, viral and fungal infections

Question 25

What is the result of superantigen activation of Th cells?

Answer 25

Massive Th-cell activation and cytokine release, resulting in shock

Question 26

Which cytokine induces naive Th cells into mature Th2 cells?

Answer 26

IL-4

Question 27

What cytokines do Th2 cells produce? What properties do these cytokines share?

Answer 27

IL-4, IL-5, IL-10, and IL-13. All are anti-inflammatory and antagonize Th1 cells

Question 28

Which cytokines aid B cells in antibody production?

Answer 28

IL-4 and IL-5

Question 29

What functions do IL-4 and IL-5 from Th2 cells serve in helminth immunity?

Answer 29

IL-4 induces hellminth specific immunoglobulin (IgE) abs and IL-5 activates eiosinophils

Question 30

Which cytokine is implicated as a mediator of asthma (airway hyperresponsiveness)?

Answer 30

IL-13

Question 31

By what two main methods do CD8+ cells kill virus-infected, graft, and tumor cells?

Answer 31

Cytotoxic T cells can lyse infected cells or induce apoptosis

Question 32

Which mature immune cell has receptors for while, unprocessed antigens and does not require MHC presentation?

Answer 32

B cells, which actually present antigens themselves via MHC II to CD4+ helper cells in the process of activation, can recognize soluble or cell-associated antigens

Question 33

Which types of antigens can induce ab production by B cells without the aid of helper T cells (ie, T-cell independent response)?

Answer 33

Multivalent antigens (bacterial capsule polysaccharides, DNA, RNA, and lipids) bind many IgM (immunoglobulin M) molecules and cross-link IgM receptors on B cells

Question 34

Where does B cell differentiation occur?

Answer 34

Bone marrow

Question 35

What is the predominant ab released in the initial stages of the primary humoral response?

Answer 35

IgM. Following a lag phase either IgG, IgA or IgE appear in the secondary response

Question 36

What is class switching of antibodies?

Answer 36

The process that changes IgM to IgG, IgA or IgE

Question 37

What cells and signals are involved in class switching?

Answer 37

Th-cell CD40 ligand interacts with B-cell CD40, inducing the release of IL-4, IL-5, and INF-y which signals class switching

Question 38

X-linked hyper-IgM syndrome is an inherited disorder where the CD40 ligand on T cells is defective. How would this affect B cells?

Answer 38

Inability to perform isotype switching resulting in hypersecretion of IgM

Question 39

How would the same syndrome (hyper IgM) affect macrophages?

Answer 39

The CD40-CD40L interaction is necessary for macrophage activation by T cells. Macrophages cannot be activated, resulting in susceptibility to intracellular microbes

Question 40

What are the main steps in B-cell presentation to antigens to helper T cells?

Answer 40

Antigen-specific B cells bind to native antigen with membrane-bound immunoglobulin molecules. After internalization and processing of the antigen in an endosome, epitopes are presented on the B-cell surface via an MHC-II molecule where it is then presented to T cell

Question 41

One of the causes of severe combined immunideficiency (SCID) is a lack of functional IL-7 receptors. What cells are depleted? How is immunity affected?

Answer 41

Since T cells require IL-7 for development, both cell mediated and humoral responses would be diminished

Question 42

What would be different about the T cells in a patient with DiGeorge syndrome compared to that of a person without it? (DiGeorge syndrome results in thymic hypoplasia)

Answer 42

T cell differentiate in the thymus; abnormal thymic structure would result in a lack of T cells

Question 43

What immune cell kills infected cells lacking MHC-I proteins?

Answer 43

NK cells destroy infected cells that lose the ability to synthesize MHC-I proteins

Question 44

NK cells are activated by which cytokines?

Answer 44

IL-12 and y-INF

Question 45

Which cytokines are responsible for the increased production of C-reactive protein during an acute-phase response in innate immunity?

Answer 45

IL-1, TNF-a, and IL-6 induce the liver to produce C-reactive protein

Question 46

What cytokine is chemotactic for neutrophils?

Answer 46

IL-8 along with a complement component (C5a)

Question 47

Which cytokine has a similar function to granulocyte-macrophage colony stimulating factor (GM-CSF)?

Answer 47

IL-3 is made by activated Th cells and supports growth and differentiation of bone marrow stem cells

Question 48

The two types of immunity are innate and adaptive immunity. What cells mediate innate immunity?

Answer 48

Monocytes/Macrophages, neutrophils, natural killer (NK) cells, gamma-delta T cells