Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
167 Cards in this Set
- Front
- Back
What are PAMPs?
|
Pathogen-associated Molecular Patterns
|
|
Examples of PAMPs?
|
LPS (lipopoly saccharide); Flagellin
|
|
Where do dendritic cells come from?
|
Mature from monocyte precursors
|
|
In what region of lymph nodes are B cells found?
|
Follicles
|
|
In what region of lymph nodes are T cells found?
|
Paracortex
|
|
What are M cells?
|
Multifenestrated cells; present in lining of small intesting -- form membrane overlying lymphoid compartments within a Peyer's patch; transport antigens from lumen of gut to APCs
|
|
What are the components of the innate immunity system?
|
Physical barriers, complement system, phagocytes, natural killer cells
|
|
What are the three major physical barriers in the innate immune system?
|
Skin, GI tract, respiratory tract
|
|
Where do macrophages come from?
|
Monocyte precursors that migrate into tissues
|
|
What is the process by which leukocytes are recruited to the site of an infection?
|
Macrophages secrete TNF and IL1 etc., causing endothelial cells to produce other proteins that make rolling leukocytes stick
|
|
What is the role of cytokines in innate immunity?
|
Mediate the early inflammatory reactions to microbes and promote elimination of microbes
|
|
Are cytokines used in innate or adaptive response?
|
BOTH
|
|
What is the role of cytokines in adaptive response?
|
Stimulate proliferation and differentiation of antigen-stimulated lymphocytes and activate specialized effector cells
|
|
What is chronic granulomatous disease?
|
Phagocytes lack the oxidases necessary to kill ingested gram + bacteria
|
|
What cytokines are involved in innate immunity?
|
IL-12 and IFN-γ
|
|
What is ADCC?
|
Antibody dependent cytotoxicity; how natural killer cells and eosinophils are signaled to lyse cells; involves recognition of Fc regions of bound antibodies by NK or eosinophils
|
|
What class of immunoglobin signals NK cells?
|
IgG
|
|
What class of immunoglobin signals eosinophils?
|
IgE
|
|
What do NK cells secrete as a signaling molecule? What cells respond to it?
|
IFN-γ; activates macrophages
|
|
What do NK cells respond to?
|
IL-12
|
|
What is the purpose of NK cells?
|
Eliminate reservoirs of infection
|
|
How do NK cells kill their targets?
|
Release perforin
|
|
How are normal cells spared from NK action?
|
MHC class I inhibits NK cell action
|
|
What are TLRs?
|
Toll-like receptors;serve as pattern recognition receptors for cells of innate immune system
|
|
What recognizes PAMPs?
|
TLRs
|
|
How does an innate immune response lead to an adaptive immune response?
|
Macrophages and dendritic cells express costimulators and secrete cytokinds that together activate T lymphocytes (signals 2 and 3)
|
|
What is the basic function of a helper T lymphocyte?
|
Activate macrophages and B cells
|
|
What is the basic function of a Cytolytic T lymphocyte?
|
Kill infected cells and eliminate reservoirs of infection
|
|
What is the basic function of a B lymphocyte?
|
Secrete antibodies that block infections and promote elimination of extracellular microbes
|
|
What are the three pathways of complement activation?
|
Classical, Alternative, MBL
|
|
What is the hallmark of the classical complement pathway?
|
Triggered by antibodies that bind pathogens (ie part of adaptive response)
|
|
What is the part of the complement system that promotes obsonization?
|
C3b binding (also coated with C4d, iC3b, and C3dg)
|
|
What is the function of the MAC complex formed by the late components of complement?
|
Osmotic lysis of the microbe
|
|
What initiates the classical complement cascade?
|
C1 must bind two or more Fc portions of IgM or IgG that are bound to antigen
|
|
What are the three responses that complement triggers?
|
Lysis, Phagocytosis, and Inflammation
|
|
What is the first common step of all three complement pathways?
|
Production of C3b
|
|
What component of complement stimulates inflammation?
|
C5a (also C4a and C3a)
|
|
How are immune complexes (opsonized antigen-antibody complexes) cleared from bloodstream?
|
Erythrocytes bind the complexes and carry then to spleen or liver where the complexes are cleared by the resident phagocytic cells (eg Kupffer cells in liver)
|
|
What is the effect of attaching C3d to microbial antigens in a nonimmune host?
|
Amplifies T-dependent B cell response to that antigen
|
|
What is the order of activation of the components of the classical complement pathway?
|
C1, C4, C2, C3, C5, C6, C7, C8, C9
|
|
How is the alternative complement pathway activated?
|
C3b binding to various activating surfaces (note that C3b is constantly being produced as part of innate immune response)
|
|
How is the lectin complement pathway activated?
|
Activates C4 in absence of antibody, then follows classical pathway; triggered by binding mannose on pathogen surfaces
|
|
What forms the MAC?
|
Multiple C9 molecules
|
|
What inhibits C1 activation?
|
C1INH-
|
|
What inhibits the convertases involved in complement?
|
DAF and Factor1
|
|
What inhibits the MAC
|
CD59 and S protein
|
|
What is angioneurotic edema?
|
Hereditary failure in regulation of C1 activity by C1 INH-
|
|
What is paroxysmal nocturnal hemoglobinuria?
|
Absense of functional DAF on erythrocytes (normally inhibits formation of C3 convertases)
|
|
What defects in complement lead to hemolytic anemia and strokes?
|
Deficiency of CD59, which normally inhibits formation of the MAC
|
|
What structural difference is there between IgM and IgG?
|
IgM has one more heavy chain C region domain; has C-terminal transmembrane and cytoplasmic portions that anchor molecule in plasma membrane
|
|
Where do the highly variable regions of antibody molecules map to?
|
The parts of the antigen binding surface loops (CDR1, CDR2, CDR3) that make the most contacts with antigen
|
|
What is CDR?
|
"Complementarity determining regions" -- highly variable regions of antibody molecules that make the most contacts with antigen
|
|
What proteins mediate recombination of antibody molecules?
|
RAG1 and RAG2 ("recombinase activating gene")
|
|
How many chromosomes are used to make antibody molecules?
|
Only One!
|
|
Genetic difference between heavy and light chain recombination?
|
Light chain gnes do not have D segments; two separate light chain loci (only one for heavy chain)
|
|
What is junctional diversity?
|
Result of inexact RAG-mediated cutting -- leads to different DNA sequences
|
|
About how many different antigen combining regions can be made?
|
10E23!
|
|
What is the process by which additional variability is introduced into IgV regions, and is associated with increased affinity for the antigen?
|
Somatic Hypermutation
|
|
Where is AID expressed?
|
Only in B cells
|
|
What is necessary for somatic hypermutation?
|
AID protein (specific for B cells)
|
|
What processes does AID mediate?
|
somatic hypermutation and immunoglobulin heavy chain isotype switching
|
|
What form of Ig is expressed ona Pre-B cell?
|
cytoplasmic mu and pre-B receptor-associated mu
|
|
What form of Ig is expressed on an immature B cell?
|
Membrane IgM (mu and kappa or lambda light chain)
|
|
What form of Ig is expressed on a Pro-B cell?
|
none
|
|
What form of Ig is expressed on a mature B cell (not activated)?
|
Membrane IgM or IgM and IgD
|
|
What provides second signal to B cells?
|
CD4+ T cells
|
|
Where does affinity maturation occur?
|
Germinal centers of follicles
|
|
What signals drive class switching of B cells?
|
CD40-CD40L and cytokines
|
|
[go through class switching and antigen recombination in book!]
|
|
|
Are RAG proteins involved in class switching?
|
No
|
|
What is the effector function of IgM?
|
Activation of classical complement pathway
|
|
What is the effector function of IgG?
|
Neutralization of microbes and toxins; opsonization to promote phagocytosis; activation of classical complement pathway; Feedback inhibition of B cell activation
|
|
What is the effector function of IgE?
|
Immunity against helminths (activation of eosinophils); Mast cell degranulation
|
|
What is the effector function of IgA?
|
Mucosal immunity (transport of IgA through epithelia)
|
|
What part of antibody structure changes during isotype switching?
|
C regions
|
|
What part of antibody structure changes during affinity maturation?
|
V regions
|
|
Where do naïve T cells preferentially migrate to?
|
Lymph nodes
|
|
Where do newly activated T cells preferentially migrate to?
|
Circulation
|
|
Where do effector and memory T cells in blood preferentially move to?
|
Peripheral tissues
|
|
[look up terminal deoxyribonucleotide transferase]
|
|
|
How does AID promote somatic hypermutation?
|
Converts C nucleotides to uridine (U), causing mutation by base pair substitution
|
|
What causes IgM and IgD to be co-expressed?
|
No stop site is present between mu and delta regions
|
|
What form of Ig is never secreted?
|
IgD
|
|
What triggers affinity maturation and class switching on B cells?
|
CD40-CD40L interaction between B and T cells
|
|
What cells can function as APCs?
|
Macrophages, dendritic cells, B cells
|
|
What are the MOST efficient APCs?
|
Dendritic cells
|
|
What is an example of an "MHC-like" molecule?
|
CD1; presents lipid antigens to unique population of lymphocytes
|
|
What cells recognice MHC class I molecules?
|
CD8+ T cells (CTLs)
|
|
What are the alleles for the MHC class I molecules?
|
HLA-A, B, C
|
|
Which MHC molecules are expressed on all nucleated cells?
|
Class I
|
|
what are the components of a MHC class I molecule?
|
single polymorphic heavy (alpha) chain and non-MHC encoded, non-polymorphic light chain called beta-2-microglobulin
|
|
What are the components of a MHC class II molecule?
|
Alpha and beta chains, both polymorphic
|
|
What cells express MHC class II?
|
APCs and thymic epithelial cells
|
|
What are the alleles for class II MHC?
|
DP, DQ, DR
|
|
What is another name for helper T cells?
|
CD4+ T cells
|
|
Peptides that end up in the cleft of MHC class I generally arise from:
|
proteins that are synthesized in the cell (can also contain peptides from proteins that escaped phagosomes)
|
|
Peptides that end up in the cleft of MHC class II generally arise from:
|
proteins that are made externally to the cell then taken up by professional APCs
|
|
What is the class II invariant chain protein?
|
Protein that stabilizes a newly synthesized class II MHC molecule before it fuses with an endosome containing broken down peptides from ingested antigens
|
|
What are TAPs?
|
The special transporters that transport peptide fragments into the ER where they bind to newly synthesized class I MHC molecules
|
|
How do DCs take up material that they will then present to T cells?
|
Macropinocytosis
|
|
What is DM protein? (involved with class II MHC proteins
|
present in endosomes that fuse with vesicles containing just-synthesized MHC class II molecules; competes for binding with invariant chain, freeing up binding site for antigenic peptide
|
|
What is the result of a TAP deficiency?
|
Variant of SCID; No peptides present in ER for class I MHC to bind
|
|
What is bare lymphocyte syndrome?
|
Variant of SCID; failed expression of MHC class II molecules
|
|
What is MHC restriction?
|
Idea that T cells are specific to self MHC molecules
|
|
How can you distinguish between T cells, B cells, and NK cells (in a lab)?
|
Cell surface markers stained by monoclonal antibodies
|
|
What are the two chains of the TCR?
|
alpha and beta
|
|
What gene segments are combined for the alpha chain of the TCR?
|
V, J, and C
|
|
What gene segments are combined for the beta chain of the TCR?
|
V, D, J, and C
|
|
What are the two chains of the BCR?
|
heavy and light
|
|
Major difference in binding between TCR and BCR?
|
TCR binds to peptide+MHC, and requires simultaneous binding of CD4 or CD8 to MHC; (BCR binds to just peptide, no requirement for simultaneous binding)
|
|
What is the alternate form of the TCR expressed by a minority of T cells?
|
gamma/delta; often responds to lipid instead of peptide antigens
|
|
What are Natural Killer T cells? What is their function?
|
Cells that have the surface markers of both T cells and NK cells; Critical for protection against autoimmunity and cancer
|
|
What are CD3 chains?
|
Series of proteins found in association with TCRs; responsible for initiating signal transduction
|
|
What is responsible for initiating signal transduction (activating the cell) after a T cell binds to MHC+peptide?
|
CD3 chains and CD4
|
|
What molecules play the role of co-stimulation (signal 2) for T cells being activated by APCs?
|
CD28 is receptor, B7 is ligand (on activated APCs)
|
|
What is necessary for T cell activation?
|
MHC-TCR interaction PLUS B7-CD28 interaction
|
|
What is the role of CD40/CD40L?
|
Activated T cells upregulate expression of CD40L; When this interacts with CD40 on an APC, that APC becomes activated to express more B7
|
|
What is CTLA4?
|
Molecule on T cells that is expresed late in the activation process; Binds B7 more avidly than does CD28, thus preventing CD28 signaling and terminating the T cell response (makes cell anergic)
|
|
What is the ITAM? (relates to T cell activation)
|
Specific domain within CD3 proteins that is responsible for initiating signal pathways
|
|
What is IL-2?
|
Interleukin-2; produced by activated T cells; promotes proliferation of T cells
|
|
How does TCR stimulation affect IL-2 interactions?
|
Stimulation causes production of IL-2 as well as expression of alpha chain of receptor, which makes receptor high-affinity; signaling results in cellular proliferation
|
|
What markers do immature T cells entering the thymus express?
|
None; negative for CD3, CD4, and CD8
|
|
How does homing of T cells occur?
|
Naïve T cells express L-selectin, which targets them to lymph nodes; after activation, E and P selectins are expressed, which target the cells to the site of infection
|
|
How do CTLs effect death of target cells?
|
Release granules containing perforin and granzymes (initate apoptosis) into target cells when restimulated by MHC class I presenting the antigen to which they are primed
|
|
What is anergy?
|
The state in which a lymphocyte has lost the ability to be stimulated; produced by receiving signal 1 without signal 2
|
|
What is the principal action of IL-4?
|
B cell switching to IgE
|
|
What is the principal action of IL-5?
|
Activation of eosinophils
|
|
What is the principal action of IFN-gamma?
|
Activation of macrophages
|
|
What is the principal action of TGF-beta?
|
Inhibition of T cell activation
|
|
If a naïve T cell is stimulated in the absence of TGF-beta but the presence of IFN-gamma and/or IL-12, what type of effector cells will develop?
|
Th1
|
|
If a naïve T cell is stimulated in the absence of TGF-beta but the presence of IL-4, what type of effector cells will develop?
|
Th2
|
|
If a naïve T cell is stimulated in the presence of TGF-beta and IL-6, what type of effector cells will develop?
|
Th17
|
|
If a naïve T cell is stimulated in the presence of TGF-beta and in the absence of IL-6, what type of effector cells will develop?
|
Treg cells
|
|
What is the dominant transcription factor for Th1 cells?
|
T-bet
|
|
What is the dominant transcription factor for Th2 cells?
|
Gata-3
|
|
What is the dominant transcription factor for Th17 cells?
|
ROR-gamma
|
|
What is the dominant transcription factor for Treg cells?
|
FoxP3
|
|
What do Th1 cells do?
|
activate macrophages to kill engulfed bacteria
|
|
What do Th2 cells do?
|
stimulate B cells to make antibody and class switch
|
|
What are the major cytokines produced by Th1 cells?
|
IFN-gamma and IL-2
|
|
What are the major cytokines produced by Th2 cells?
|
IL-4 and IL-5
|
|
Imbalance in what T cell effector group often leads to inflammatory diseases?
|
Th1
|
|
Imbalance in what T cell effector group often leads to allergic responses?
|
Th2
|
|
What is the major cytokine produced by Th17 cells?
|
IL-6 and IL-17
|
|
What seems to result from uncontrolled activity of Th17 cells?
|
autoimmunity
|
|
What do Th17 cells do?
|
Stimulate neutrophil recruitment
|
|
Note that CD4+ T cell subsets negatively regulate each other
|
|
|
What type of T cells can be subdivided into several subgroups based on the cytokines they produce?
|
CD4+ T cells
|
|
What is the difference between long-lived plasma cells and memory cells?
|
Memory cells can be any type of T or B cells; do NOT secrete anything. Plasma cells are B cells that continue to secrete small amounts of antibodies
|
|
How is apoptosis stimulated in T cells?
|
Engagement of Fas (CD95) receptor on activated T cells signals for apoptosis
|
|
What is AIRE?
|
Transcription factor involved in expression of self-antigens in thymus; genetic abnormalities result in auto-immune disease
|
|
What is APECED?
|
Autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia; caused by genetic abnormality in AIRE gene
|
|
In a primary immunodeficiency, upper and lower resp infections indicate what kind of deficiency?
|
B cell
|
|
In a primary immunodeficiency, obligate intracellular organisms indicate what kind of deficiency?
|
T cell
|
|
In a primary immunodeficiency, unusual bacteria indicate what kind of deficiency?
|
Neutrophils
|
|
If your IgG is less than 100mg/dl and you have no IgA or IgM, what do you have?
|
X-linked Agammaglobulinemia
|
|
If you don't have tonsils because of a congenital abnormality, what do you have?
|
X-linked Agammaglobulinemia
|
|
Chronic Granulomatous Disease is a disorder of what?
|
The INNATE immune system; can't make ROS to kill engulfed bad stuff in phagocytes
|
|
What is a type I hypersensitivity?
|
Allergies… IgE mediated; over stimulation of mast cells
|
|
What is a type II hypersensitivity?
|
Antibody mediated but not IgE; tissue damage and inflammation
|
|
What is a type III hypersensitivity?
|
immune complexes get deposited in blood vessels, cause inflammation
|
|
What is a type IV hypersensitivity?
|
T cell dependent
|
|
What type of antibody dominates in a secondary response (as compared with a primary response)?
|
IgG
|
|
What are the advantages and disadvantages of live attenuated virus vaccines?
|
Good immunogens that induce long-lied, appropriate immunity BUT are biochemically and genetically unstable and often not possible to produce; dangesrs of contamination or reversion to virulence
|
|
What are the advantages and disadvantages of inactivated vaccines?
|
Stable with little or no risk of virulence BUT not possible for all viruses and not as effective as live attenuated; does not create mucosal or cell immunity and often need reimmunization
|
|
What are the advantages and disadvantages of using fragments or sub-unit vaccines?
|
Safe BUT poor antigenicity and problems with vaccine delivery into body
|
|
What cells are responsible for tumor immunity?
|
T cells
|