GenPath Chapter 6 Flashcards
(24 cards)
Where are toll-like receptors found?
Plasma membrane and endosomal vesicles
All TLRs signal by a common pathway that culminates in teh activation of two sets of transcription factors….
- NF-kB (stimulates the synthesis and secretion of cytokines and the expression of adhesion molecules)
- Interferon regulatory factors (IRFs) that stimulate the production of the antiviral cytokines, type I interferons
What are NOD-like receptors?
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
WHat is the inflammasome?
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
Function of NK cells?
To recognize and destroy severely stressed/abnormal cells (e.g. virus-infected cells and tumor cells)
…make up 5-10% of peripheral blood lymphocytes
What markers to NK cells express?
CD16 (receptor for IgG Fc tails that confers on NK cells the ability to lyse IgG-coated target cells)
Activating/inhibitory receptors of NK cells?
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
Which cytokines to NK cells secrete?
IFN-gamma
….which activated macrophages to destroy ingested microbes, and thus NK cells provide an early defense against intracellular microbial infections
Which cytokines regulate NK cell activity?
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**
What generates antigen receptor diversity?
Somatic recombination of the genes that enode antigen receptors
Which enzyme mediates recombination in lymphocytes (for receptors)
RAG1 and RAG2 (recombination-activating genes)
inherited defects in RAG proteins result in a failure to generate mature lymphocytes
There are 3 major populations of T cells, name them and their function
- Helper T cells; stimulate B lymphocytes to make antibodies and activate leukocytes (e.g. phagocytosis) to destroy microbes
- Cytotoxic (killer) T cells: kill infected cells
- Regulatory T lymphocytes: limit the immune responses and prevent reactions against self antigens
For T cells to respond, what is the second signal?
1st signal: Recognize antigen MHC complexes, additional signals provided by antigen-presenting cells
2nd signal: CD28
For B cells to respond, what is the second signal?
Signal 1: antigen binding
CD21 is a receptor for complement component that also promotes B-cell activation
What are Langehans cells?
Immature dendritic cells within the epidermis
List the features that make dendritic cells good at antigen detection?
- Located under epithelial (common site of entry of microbes) and in interstitia of all tissues (where antigens may be produced)
- Express many receptors for capturing and responding to microbes (e.g. TLRs, lectins)
- DCs are recruited to the T-cell zones of lymphoid organs - to present antigen to naive T cells
- DCs express high levels of MHC and other molecules needed for antigen presentation and T-cell activation
What is a follicular dendritic cell (FDC)
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
What is the function of MHC molecules?
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
Difference in Class I and Class II MHC?
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
Which cytokine do CD4 T cells secrete ?
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
CD4 cells once activated can differentiate into effector cells
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
Upon activation, which proteins do eosinophils liberate?
Major basic protein
Eosinophil cationic protein
…which damage tissues
What types of crystals do eosinophils produce?
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
Activation of lymphocytes requires ___ signals
two
- 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
- 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
