GenPath Chapter 6

Question 1

Where are toll-like receptors found?

Answer 1

Plasma membrane and endosomal vesicles

Question 2

All TLRs signal by a common pathway that culminates in teh activation of two sets of transcription factors….

Answer 2

1. NF-kB (stimulates the synthesis and secretion of cytokines and the expression of adhesion molecules)
2. Interferon regulatory factors (IRFs) that stimulate the production of the antiviral cytokines, type I interferons

Question 3

What are NOD-like receptors?

Answer 3

Cytosolic receptors named after the founding member NOD-2

Recognize a wide variety of substances (products released from necrotic/damaged cells such as uric acid, ATP, loss of intracellular K ions, some microbial products)

NLRs signal via a cytosolic multiprotein complex called the inflammasome

Question 4

WHat is the inflammasome?

Answer 4

It is a multiprotein complex in the cytosol triggered by signaling from NOD-like receptors

–> activates capase-1 that cleaves a precursor form of the cytokine interleukin-1 (IL-1) to generate the biologically active form

recognition of urate crystals by a class of NLRs underlies the inflammation associated with gout

Question 5

Function of NK cells?

Answer 5

To recognize and destroy severely stressed/abnormal cells (e.g. virus-infected cells and tumor cells)

…make up 5-10% of peripheral blood lymphocytes

Question 6

What markers to NK cells express?

Answer 6

CD16 (receptor for IgG Fc tails that confers on NK cells the ability to lyse IgG-coated target cells)

Question 7

Activating/inhibitory receptors of NK cells?

Answer 7

Inhibitory receptors recognize MHC class I molecules (expressed on all healthy cells); these inhibitory receptors prevent the NK cells from killing normal cells

Virus/neoplastic transformation reduce the expression of class I MHC molecules –> NK cells engage tehse abnormal cells and the infected or tumor cell is killed

Question 8

Which cytokines to NK cells secrete?

Answer 8

IFN-gamma
….which activated macrophages to destroy ingested microbes, and thus NK cells provide an early defense against intracellular microbial infections

Question 9

Which cytokines regulate NK cell activity?

Answer 9

IL-2
IL-15
IL-12

• *IL2 and IL15 stimulate proliferation of NK cells**
• *IL-12 activates the killing of target cells and the secretion of IFN-gamma**

Question 10

What generates antigen receptor diversity?

Answer 10

Somatic recombination of the genes that enode antigen receptors

Question 11

Which enzyme mediates recombination in lymphocytes (for receptors)

Answer 11

RAG1 and RAG2 (recombination-activating genes)

inherited defects in RAG proteins result in a failure to generate mature lymphocytes

Question 12

There are 3 major populations of T cells, name them and their function

Answer 12

1. Helper T cells; stimulate B lymphocytes to make antibodies and activate leukocytes (e.g. phagocytosis) to destroy microbes
2. Cytotoxic (killer) T cells: kill infected cells
3. Regulatory T lymphocytes: limit the immune responses and prevent reactions against self antigens

Question 13

For T cells to respond, what is the second signal?

Answer 13

1st signal: Recognize antigen MHC complexes, additional signals provided by antigen-presenting cells

2nd signal: CD28

Question 14

For B cells to respond, what is the second signal?

Answer 14

Signal 1: antigen binding

CD21 is a receptor for complement component that also promotes B-cell activation

Question 15

What are Langehans cells?

Answer 15

Immature dendritic cells within the epidermis

Question 16

List the features that make dendritic cells good at antigen detection?

Answer 16

1. Located under epithelial (common site of entry of microbes) and in interstitia of all tissues (where antigens may be produced)
2. Express many receptors for capturing and responding to microbes (e.g. TLRs, lectins)
3. DCs are recruited to the T-cell zones of lymphoid organs - to present antigen to naive T cells
4. DCs express high levels of MHC and other molecules needed for antigen presentation and T-cell activation

Question 17

What is a follicular dendritic cell (FDC)

Answer 17

Bear Fc receptors for IgG and receptors for C3b

Can trap antigen bound to antibodies or complement proteins

Role in humoral immune responses by presenting antigens to B cells in the germinal center

Question 18

What is the function of MHC molecules?

Answer 18

To display peptide fragments of protein antigens for recognition by antigen-specific T cells

..fundamental to antigen recognition by T cells and are linked to many autoimmune diseases

Question 19

Difference in Class I and Class II MHC?

Answer 19

CLass 1 MHC molecules display peptides that are derived from cytoplasmic proteins (including normal proteins and virus- and tumor-specific antigens, that are all recognized bound to class I MHC molecules by CD8+ T cells

Class 2 MHC molecules present antigens derived from extracellular microbes and proteins following their internalization into endosomes or lysosomes

Question 20

Which cytokine do CD4 T cells secrete ?

Answer 20

IL-2 (IL-2 acts as a growth factor to simulate T-cell proliferation)

The T cells will also express CD40L - which engages CD40 on macropahges or B cells and activates these cells

Question 21

CD4 cells once activated can differentiate into effector cells

Answer 21

Th1 subset secrete cytokine IFN-gamma (potent macrophage activator
(combination of CD40- and IFN-gamma are the “classical” macrophage activation)

Th2 cells produce IL-4, which stimulates B cells to differentiate into IgE-secreting plasma cells and IL-5 which stimulates production of eosinophils
(Th2 also induce the “alternative macrophage activation pathway - associated with tissue repair and fibrosis)

Th17 cells secrete IL-17, recruit neutrophils and monocytes (that destroy extracellular bacteria and fungi) and are involved in some inflammatory diseases

Question 22

Upon activation, which proteins do eosinophils liberate?

Answer 22

Major basic protein
Eosinophil cationic protein

…which damage tissues

Question 23

What types of crystals do eosinophils produce?

Answer 23

Charcot-Leyden crystals

composed of protein galectin-10 (which are somtimes released into the extracellular space and can be detected in the sputum of patients w/ asthma)

these crystals promote inflammation and enhance Th2 responses, so they may contribute to allergic reactions

Question 24

Activation of lymphocytes requires ___ signals

Answer 24

two

1. Recognition of peptide antigen in association with self MHC molecules on the surface of APCs and a set of costimulatory signals (“second signals”) from APCs
2. Second signals are provided by certain T cell-associated molecules, such as CD28 taht bind to their ligands

if the antigen is presented to T cells without adequate levels of costimulatory molecules then cells become anergic