Reading...
Play button
Play button
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;
221 Cards in this Set
- Front
- Back
|
All leukocytes derive from what stem cell type?
|
hematopoetic stem cells
|
|
|
thick fluid layer composed of glycoproteins and enzymes
|
mucus
|
|
|
The mucosa is slightly _____ vulnerable to microbial invasion.
|
more
|
|
|
What are the three granylocyte types
|
neutrophils, basophils, and eosinophils
|
|
|
Granulocytes are also called
|
polymorphonuclear leukocytes
|
|
|
Which granulocytes are specialized for phagocytosis of microorganisms?
|
neutrophils
|
|
|
Which granulocytes protect against multicellular parasites (Helminths)?
|
eosinophils
|
|
|
These are not granulocytes but respond to allergic reactions
|
mast cells
|
|
|
What do mast cells release to react to allergies?
|
histamine
|
|
|
Monocytes circulate in the ______.
|
blood
|
|
|
Macrophages circulate in the _____.
|
tissue
|
|
|
Dendritic cells start out in the _____ before migrating to lympho node to activate the _____ immune response.
|
lymph; adaptive
|
|
|
The innate immune response is mediated by _____.
|
inflammation
|
|
|
What do soluble proteins of the innate immune system do?
|
mark pathogens for phagocytosis and recruit phagocytic cells
|
|
|
First phagocytic cell to respond to infection
|
macrophage
|
|
|
Other than eating pathogens, what can macrophages do to decrease pathogen numbers?
|
secrete cytokines that recruit neutrophils and other leukocytes
|
|
|
Where are neutrophils stored before being released to fight the infection?
|
bone marrow
|
|
|
What organ filters out old/damaged RBCs?
|
spleen
|
|
|
How does the spleen come into contact wth pathogens and lymphocytes?
|
through the blood, b/c it doesn't have an afferent lymphatic vessel
|
|
|
What kinds of cells can T helper cells activate?
|
B cells and macrophages
|
|
|
Soluble immunoglobulins secreted by effector B cells (plasma cells)
|
antibodies
|
|
|
Effector B cells are AKA..?
|
plasma cells
|
|
|
Anything recognized by immunoglobulin or T-Cell receptors
|
antigen
|
|
|
Antibody-mediated coating to facilitate phagocytosis
|
opsonization
|
|
|
What 2 things can antibodies do?
|
neutralize toxins and viral particles AND opsonize pathogens
|
|
|
Peptides of the innate immune system that penetrate microbial membranes and distrupt their integrity
|
defensins
|
|
|
What are defensins secreted by?
|
epithelial cells of the intestinal, respiratory, urogenital tracts, skin, and neutrophils
|
|
|
Soluble proteins constitutively expressed in blood, lymph, and ECF that make up the innate immune system
|
complement
|
|
|
What are the main jobs of the complement system
|
tagging bacterium for destruction and recruiting phagocytes
|
|
|
C3_ recruits phagocytes/effector cells
|
a
|
|
|
C3_ tags pathogens and organizes MAC complexes
|
b
|
|
|
Which complement activation pathway goes to work first?
|
alternative
|
|
|
What does the classical complement activation pathway require before it can start working?
|
antibody or CRP binding to pathogen
|
|
|
All 3 complement activation pathways converge on cleavage of ___
|
c3
|
|
|
Cleavage of C3 exposes a reactive ______ bond
|
thioester
|
|
|
If the thioester bond on C3b is attacked by _____ or ____ groups on the pathogen, C3b will bind to that pathogen's surface.
|
hydroxy or amino
|
|
|
C3 is secreted by which organ before circulating throughout the body?
|
liver
|
|
|
What is the soluble C3 convertase used in the alternative pathway?
|
iC3Bb
|
|
|
What binds to C3bBb, preventing its degradation?
|
Properdin
|
|
|
What binds to C3b, causing conformation change allowing cleavage by factor I and production of inactive C3b (iC3b)?
|
Factor H
|
|
|
What binds to C3bBb, causes dissociation of Bb
|
Decay-accelerating factor
|
|
|
What binds to C3bBb, attracts factor I to make iC3b?
|
membrane co-factor protein (MCP)
|
|
|
What receptor on macrophages binds C3b to begin phagocytic process?
|
CR1 (complement receptor 1)
|
|
|
Class 1 complement control proteins interact with what type of C3b?
|
bound
|
|
|
Class 2 complement control proteins bind to what kind of complement?
|
unbound
|
|
|
What is C5 convertase?
|
C3b^2Bb, which is C3b + C3 convertase
|
|
|
What initiates membrane attack complex?
|
C5b
|
|
|
How are DAF, HRF, and CD59 linked to the plasma membrane?
|
glycophosphatidylionositol lipid tails
|
|
|
What do human cells secrete to prevent C5b67 from associating with the membrane?
|
S protein, clusterin, and factor J
|
|
|
What do human cells express to bind to C5b678 to prevent polymerization of C9?
|
CD59 (Homologous restriction factor -HRF)
|
|
|
What do C3a and C5a do?
|
cause acute inflammation, call phagocytes, increase permeability of blood vessels to allow phagocyte influx, increase expression of CR1 on phagocytes
|
|
|
These cyclic homonpentamers bind non-covalently to pathogens and receptors of phagocytes, much like antibodies
|
pentraxins
|
|
|
Many pathogens express _____ to chop up complement, coagulation, and other serum proteins.
|
proteases
|
|
|
Immunoglobulins are proteins made by ____.
|
b cells
|
|
|
Where are immunoglobulins expressed?
|
on the surface of B cells
|
|
|
What are antibodies?
|
immunoglobulins that are secreted into the blood instead of being expressed on the b cell surface
|
|
|
The variable region of the immunoglobulin is where?
|
at the end (antigen-binding end) or the immunoglobulin
|
|
|
The immunoglobulin classes are defined by what?
|
Type of constant region
|
|
|
Largest IG class
|
IgM
|
|
|
Most abundant ig class
|
IgG
|
|
|
Ig class that is primary activator of complement
|
IgM
|
|
|
Only Ig that can cross placenta
|
IgG
|
|
|
Most abundant IgG
|
IgG1
|
|
|
How many subclasses does IgG have?
|
4
|
|
|
IgG class best at activating complement but most susceptible to proteolysis due to hinge region
|
IgG3
|
|
|
Monovalent IgG
|
IgG4
|
|
|
Ig class that protects mucosal surfaces, can be dimeric, and is secreted into the gut, milk, tears, and sweat
|
IgA
|
|
|
What confers the specificity of immunoglobulins?
|
complementarity determining regions (CDRs) in the Ig variable regions
|
|
|
The part of the antigen to which the antibody binds
|
epitope |
|
|
The sequence of _____ determines the shape of the binding site.
|
the CDRs
|
|
|
V domains are encoded by how many gene segments in light chains?
|
2 (V and J)
|
|
|
V domains are encoded for by how many gene segments in heavy chains?
|
3 (V, J, D)
|
|
|
Naïve B cells express membrane bound IgM and IgD via what process?
|
alternative RNA splicing
|
|
|
What are the 2 light chain genes?
|
lambda and kappa
|
|
|
How many recombination events do light chains have?
|
1
|
|
|
How many recombination events do heavy chains have?
|
2
|
|
|
What are the heavy chain recombination events?
|
D-J, then V-DJ
|
|
|
What is allelic exclusion?
|
The fact that naïve B cells express only 1 light chain and 1 heavy chain
|
|
|
What is the B cell receptor constituted of?
|
Surface Ig plus Igbeta and Igalpha
|
|
|
How does the B cell receptor work?
|
The surface Ig recognizes the antigen and the Igalpha and Igbeta transmit the signal inside the cell
|
|
|
What causes antigen affinity?
|
mutations in CDRs due to somatic hypermutation
|
|
|
What causes somatic hypermutation?
|
Pathogen recognition, which turns on AID (activation-induced cytidine deaminase)
|
|
|
AID is expressed only in ____ cells.
|
B
|
|
|
The selection process used to preferentially differentiate only those B cells in which the somatic hypermutation process created better antigenic affinity
|
affinity maturation
|
|
|
When certain cytokines stimulate transcription factor binding, which creates a new segment that can allow the immunoglobulin to switch types
|
isotype switching
|
|
|
How is double stranded DNA repaired?
|
non-homologous end joining
|
|
|
TCR receptors only recognize proteins that are in what state?
|
degraded into peptides and presented by MHC
|
|
|
What do CD4+ T cells do?
|
activate macrophages to phagocytose and secrete cytokines, and stimulate B cells to secrete antibodies
|
|
|
Do CD4 T cells secrete cytokines?
|
yes
|
|
|
The TCR alpha chain is similar to the immunoglobulin ____ chain
|
light
|
|
|
The TCR beta chain is similar to the immunoglobulin ___ chain.
|
heavy
|
|
|
Why is the TCR repertoire more diverse than the Ig repertoire?
|
TCR has greater number of V and J segments
|
|
|
If you inhibit CD3, you inhibit what?
|
the recognition of antigens
|
|
|
The sigma gene segments are located within the _____ chain locus, so rearrangement of the __ chain results in deletion of the sigma gene
|
alpha
|
|
|
Is y:o TCR recognition dependent on MHC peptide complex?
|
no
|
|
|
CD__ interacts with MHC class 1
|
8
|
|
|
CD__ interacts with MHC Class II
|
4
|
|
|
_____ act as binding sites for T cell co-receptors.
|
MHCs
|
|
|
TCR is specific for what?
|
MHC + peptide complex
|
|
|
_____ have promiscuous binding affinity, meaning they can bind peptides with many different AA sequences
|
MHC
|
|
|
MHC ___ presents antigens from extracellular pathogens
|
II
|
|
|
MHC __ presents antigens from intracellular pathogens
|
I
|
|
|
______ pathogens are processed first through the cytosol into the ER before being presented at the cell surface
|
intracellular
|
|
|
_____ antigens are taken in by endocytosis and made into peptides in phagolysosomes before being presented at the cell surface
|
extracellular
|
|
|
Cytosolic antigenic peptides are transported into the ER via ___
|
TAP - transporter associated with antigen processing
|
|
|
In infected tissues, cells of the innate immune system secrete ____.
|
IFN-y
|
|
|
INF-y does what?
|
Induces gene expression that compromises the immunoproteasome
|
|
|
____ cleaves the antigenic amino acids so that they fit beffer on the MHC class I molecule before it travels to the cell surface
|
ERAP (endoplasmic reticulum aminopeptidase)
|
|
|
What are the antigen-presenting cells?
|
macrophages, Dendritic Cells, B-Cells
|
|
|
_____ binds to MHC II, releases CLIP, and allows foreign peptide to bind.
|
HLA-DM
|
|
|
MHC __ is expressed only on cells that specialize in antigenic uptake.
|
II
|
|
|
MHC __ is expressed on virtually all cell types because virtually all cells are subject to viral infection.
|
I
|
|
|
Cross-presentation allows exogenous peptides to be expressed by MHC ___ molecules.
|
I
|
|
|
Do MHCs undergo gene rearrangement?
|
no
|
|
|
HLA_,_, and _ are for MHC I
|
A, B, C
|
|
|
HLA_,_, and _ are for MHC II
|
DP, DQ, DR
|
|
|
Genes that work together in MHC I presentation (HLA class I molecules, TAP, immunoproteasome) are regulated by which IFN?
|
IFN-a and IFN-b
|
|
|
Genes that work together in MHC II prsentation (HLA class II molecules) are regulated by ____
|
IFN-y
|
|
|
When a particularly nasty/virulent strain of disease selects for individuals with a certain haplotype
|
direction
|
|
|
Which type of cell has most of its population made early in a person's life?
|
T cells
|
|
|
The process by which the thymus degenerates by one year after birth
|
thymic involution
|
|
|
Signaling from ____ is necessary to drive cells along the pathway of T cell differentiation.
|
Notch1
|
|
|
For TCRs gene rearrangement, ____ cells are not subject to selection, but the ____ cells are.
|
y:o ; a:b
|
|
|
Successful TCR beta rearrangement leads to binding to what?
|
pTa (surrogate alpha chain)
|
|
|
How many chances does the TCR have to become y:o?
|
2; one during beta chain rearrangement and one during alpha chain rearrangement
|
|
|
Successful TCR alpha rearrangement results in what?
|
double positive thymocytes (express both CD4 and CD8)
|
|
|
Positive selection removes T cells that can't do what?
|
interact with the individual's MHCs
|
|
|
Receptor editing can occur during ____ selection for T cells
|
positive
|
|
|
TCRs that bind to MHC class __ become CD8 T cells
|
I
|
|
|
TCRs that bind to MHC class __ become CD4 T cells
|
II
|
|
|
TCRs that bind too tightly to MHC-self-peptide complex are induced into apoptosis in _____ selection.
|
negative
|
|
|
Negative selection is a process of _____ tolerance because it's in a lymphoid organ
|
central
|
|
|
Thymic medullary cells express ______, which is a transcription factor that ensures expression of proteins from all tissues within the thymus
|
AIRE
|
|
|
Inefficient negative selection leads to what?
|
widespread autoimmunity
|
|
|
_______ cells possess TCRs specific for self-peptide
|
Treg
|
|
|
Proteins that recognize carbohydrates
|
lectins
|
|
|
Receptors locating both inside and outside human cells that sense common pathogenic molecules and instruct macrophages to recruit additional help
|
Toll-like receptors
|
|
|
The archetypal TLR, senses LPS
|
TLR4
|
|
|
TLR4's co-receptor
|
CD14
|
|
|
What does LPS binding to TLR4-CD14 complex lead to?
|
Activation of intracellular messenger cascade resulting in transcription factor NFkB turning on inflammatory cytokine genes
|
|
|
Where are NOD-like receptors expressed?
|
cytoplasm
|
|
|
What do NOD-like receptors recognize?
|
pathogenic molecules
|
|
|
What does NOD-like receptor recognition of pathogenic bioolecules do?
|
activates intracellular signaling cascade resulting in NFkB nuclear translocation
|
|
|
What leads to formation of inflammasome?
|
Macrophage activation
|
|
|
Formation of inflammasome leads to activation of _____
|
capsases
|
|
|
Capsases produce _____.
|
active interleukins
|
|
|
Which cytokines increase vascular permeability
|
IL-1B and TNF-a
|
|
|
Which cytokines attract neutrophils to infected tissue
|
CXCL8
|
|
|
Which cytokine activates NK cells?
|
IL-12
|
|
|
Which cytokines increase temperature
|
TNF-a, IL-1, IL-6
|
|
|
What interaction causes neutrophils to stop and squeeze through the endothelium into the infected tissue
|
ICAM-1 + LFA-1
|
|
|
What does CXCL8 cause?
|
Neutrophils to continue going out of the blood into the tissues
|
|
|
How do neutrophils kill?
|
expulsion of toxic granules
|
|
|
_____ stimulates the liver to secrete acute phase proteins, such as C-reactive protein, mannose-binding lectin
|
IL-6
|
|
|
C-reactive protein and mannose-binding lectin both do what?
|
opsonize pathogens and active complement
|
|
|
Classical and lectin pathay not included in slide set - see innate-induced, slides 18-20
|
x
|
|
|
____ produced by macrophages recruits NK cells to form immunological synapse.
|
IL-12 |
|
|
____ produced by macrophages induces differentiation of NK cells into effector NK cells
|
IL-15 |
|
|
Effector NK cells secrete interferon __
|
y (gamma)
|
|
|
Interferon-y does what for macrophages
|
makes them more efficient at phagocytosis
|
|
|
_____ and ____, secreted by stromal cells, establishes a concentration gradient along the endothelial surface
|
CCL21 and CCL19
|
|
|
Binding of specific MHC:peptide complex sends signal, changes conformation of ___, and increases affinity for ____.
|
LFA-1, ICAM-1
|
|
|
______ expression is induced on antigen presenting cells by TLR signaling on the naïve T cell
|
B7
|
|
|
Once activated, T cells express ____, which binds to B7 much more strongly than CD28 does.
|
CTLA4
|
|
|
What is instrumental for all signaling events in the T cell
|
ZAP-70
|
|
|
____ signaling drives cells to replicate
|
IL-2
|
|
|
TH1 cells activate ___
|
macrophages
|
|
|
TH17 cells activate ___
|
neutrophils
|
|
|
TH2 cells helps which cells?
|
eosinophils, basophils, mast cells
|
|
|
TFH cells activate ___ cells
|
naïve B cells
|
|
|
Treg cells do what?
|
control and limit activities of other types
|
|
|
The "bad" form of tuberculosis (lepromatous) is associated with TH__.
|
2 - extracellular
|
|
|
____ is present on activated endothelial cells in infected and inflamed tissue
|
VCAM-1
|
|
|
JAK and STAT are associated with what kinds of cells?
|
Effector CD4 T cells
|
|
|
What does macrophage activation require?
|
IFNy and CD40 ligand
|
|
|
What is necessary for for B cell activation?
|
Cross-linking of BCR and stimulation of BCR co-receptor (CR2 complex)
|
|
|
Where does affinity maturation occur?
|
in the germinal center
|
|
|
Centrocytes must compete for antigen access on the FDC and ____ on the cognate T cell
|
CD40L
|
|
|
What determines whether a centrocyte becomes a plasma cell or memory cell?
|
cytokines secreted by cognate TFH cell
|
|
|
Ig_ and Ig_ are most effective at activating complement via classical pathway
|
M and G3
|
|
|
How does the classical pathway form classical C3 convertase?
|
C1 binding to antigen:antibody complex facilitates conformational change, cleaves C4 and C2
|
|
|
What makes up an immune complex?
|
complement:antigen:antibody
|
|
|
How are immune complexes removed from body?
|
RBCs pick them up and circulate through liver and spleen
|
|
|
What variety of FCyR has the highest affinity for IgG?
|
FcyRI
|
|
|
Which Fcy is the receptor for NK cells
|
FcyRIII
|
|
|
_____ protects mucosa
|
dimeric IgA
|
|
|
Numberous B cell follicles with germinal centers and associated T cell areas in the GALT
|
Peyer's patches
|
|
|
Portals in the gut through which antigens and organisms are transported
|
Microfold (M) cells
|
|
|
Gut DCs drain to the mesenteric lymph nodes and secrete what?
|
IL-10
|
|
|
What does IL-10 do?
|
prevents inflammatory cytokine secretion by T cells
|
|
|
What cells in the gut sample the environment from within the lumen?
|
DCs
|
|
|
Naïve B and T cells circulate through Peyer's patches and mesenteric lymph nodes via ____ and ____ concentration gradient
|
CCL21 and CCL19
|
|
|
IgA_ is more common in the colon
|
1
|
|
|
IgM can compensate for selective IgA deficiency by virtue of the __ chain.
|
J
|
|
|
Helminths are detected via what receptors in the intestinal epithelium
|
NOD and TLR
|
|
|
Example of virus that has a different capsular polysaccharide/serotype for every strain, so just because you have antibodies for one doesn't mean you're safe from another.
|
S. Pneumoniae
|
|
|
The influenza virus has an error-prone ____ based genome
|
RNA
|
|
|
When mutations occur randomly and often in a genome
|
antigenic drift
|
|
|
When genes from different strains recombine to form a new strain
|
antigenic shift
|
|
|
Virus is coded by >1000 genes, but only 1 is expressed at a time; when immune system recognizes one, it switches to another
|
gene rearrangement
|
|
|
Which virus uses gene rearrangement?
|
trypanasoma
|
|
|
Which three viruses use latency
|
Herpes simplex, varicella-zoster, epstein-barr
|
|
|
Which virus coats itself with human proteins?
|
treponema pallidum
|
|
|
Which virus creates its own intracellular vesicle
|
toxoplasma gondii
|
|
|
Which virus secretes pore-forming proteins
|
listeria monocytogenes
|
|
|
Which virus prevents phagosome-lysosome fusion?
|
mycobacterium tuberculosis
|
|
|
What kind of bacteria bind their entertotoxins to MHC II and TCRs to cause too many T cells to be made?
|
bacterial superantigens
|
|
|
What virus secretes SSLPs (superantigen-like proteins?)
|
staph
|
|
|
What do SSLPs do?
|
bind to IgA, preventing antibody delivery to phagocyte and binding to C5 so no mac attack
|
|
|
HIV is characterized by massive reduction in ___ cells
|
CD4 t cells
|
|
|
Which virus is a retrovirus?
|
HIV
|
|
|
Which virus relies on T cell activation?
|
HIV
|
|
|
The appearance of a-HIV antibodies in the blood
|
seroconversion
|
|
|
Antibodies that neutralize a broad range of HIV strains
|
broadly neutralizing antibodies
|
|
|
These have hypermutated CDRs
|
broadly neutralizing antibodies
|
|
|
C5-C9 diseases only affect what virus species?
|
Neisseria
|
|
|
C1-C4 defects lead to buildup of _____
|
immune complexes
|
|
|
IL-12 plays a role in activation of what?
|
NK cells, macrophages, T cells
|
|
|
Deficiency in IL-12 receptor leads to susceptibility to ____.
|
mycobacterium
|
|
|
X-linked hyper IgM syndrome is lack of what?
|
CD40 ligand
|
|
|
deficiency that leads to accumulation of nucleotide metabolites which are toxic to T cells
|
adenosine deaminase deficiency
|
