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319 Cards in this Set

  • Front
  • Back
T/F. All adaptive immune responses entail the production of antibodies.
F
The myeloid progenitor is the precursor of which cells?
granulocytes, macrophages, dendritic cells, mast cells
Which cells are chiefly important in defense against parasitic infections?
eosinophils
The common lymphoid progenitor gives rise to what cells?
lymphocytes and NK cells (also dendritic cells)
The central or primary lymphoid organs include what?
bone marrow and thymus
(B/T) cells are more lateral in the lymph node.
B; T cells are located in the paracortical area (more medial)
The red pulp of the spleen is responsible for what?
red cell disposal
Which cells of the immune system are active in innate immunity?
macrophages and neutrophils
What is the difference between cytokines and chemokines?
Cytokines – affect behavior of other cells; chemokines – attract cells
(Neutrophils/macrophages) respond to inflammation first.
neutrophils
Dendritic cells present the material that they ingest to what?
T lymphocytes
T/F. The variable region of an antibody consists only of light chain.
F. both heavy and light
T/F. Both the B and T lymphocytes generate Ig that have two antigen-recognition sites.
F. T has only 1 antigen recognition site
T/F. Both B and T lymphocytes receive co-stimmulatory molecules from dendritic cells.
F. T cells do, but naïve B cells get it from effector T cell
T/F. Activated dendritic cells are the only APC.
F. macrophages and B cells presenting foreign antigen on their surface
In general, (B/T) cells reognize bacteria and (B/T) cells recognize viruses.
B – bacteria (outside cells); T – viruses (inside cells)
Humoral immunity refers to what?
antibodies
How do antibodies deal with extracellular pathogens?
neutralization, opsonization, complement
(B/T) cells are responsible for cell-mediated immune responses of adaptive immunity.
T
Cytotoxic T cells express CD ___ on their cell surfaces.
CD8
T Helper cells express CD ___ on their cell surfaces.
CD4
Th1 cells express CD ___ on their cell surfaces and do what?
CD4; activate macrophages to induce fusion of lysosomes with vesicles containing the bacteria; release cytokines and chemokines that attract macrophages; activate B cells
`
CD4; stimulate B cells
MHC class I molecules collect peptides derived from proteins synthesized where? MHC class II?
class I – cytosol; class 2 – intracellular vesicles
Which MHC class presents viral proteins on the cell surface?
MHC class I
MHC class I is recognized by which class of T cell?
CD8 (cytotoxic); class I – viruses
MHC class II is recognized by which class of T cell?
CD4
(Macrophages/neutrophils) are the first to encounter pathogens.
macrophages; then recruit large numbers of neutrophils
What are 3 toxic products macrophages and neutrophils generate to kill engulfed microorganisms?
nitric oxide, superoxide anion, hydrogen peroxide
(Macrophages/neutrophils/both/neither) are long-lived.
macrophages
Chronic granulomatous disease patients have a genetic deficiency of what?
NADPH oxidase
How do mycobacteria evade destruction?
grow inside macrophage phagosomes by inhibit acidification and fusion with lysosomes
Inflammatory responses, such as increase in vascular diameter and expression of adhesion molecules, are mediated by (macrophages/neutrophils/both).
macrophages
Which complement factor is a chemoattractant for neutrophils and monocytes and activates phagocytes and local mast cells
C5a
Kinin and bradykinin do what?
increase vascular permeability
What is unique about bacterial DNA that allows the immune system to recognize it?
unmethylated repeats of dinucleotide CpG
What is unique about viral nucleic acids that allows the immune system to recognize it?
double stranded RNA
Pattern recognition receptors recognize what (examples)?
CpG, double stranded RNA
TLR-4 signals the presence of what?
LPS on bacteria
TLR in general recognize what?
molecular patterns that are not found in normal vertebrates
Which bacteria have LPS?
gram-
What are the three pathways that complement can be activated?
classical (direct, CRP, antigen-antibody); mannose-binding lectin; alternative (pathogen surfaces
The classical pathway involves which complement factor?
C1q
The alternative pathway involves which complement factor?
C3
The three pathways of complement activation converge on which protease?
C3 convertase
In the context of complement, the smaller cleage fragment is designated as (a/b).
a (remember: b – Big)
Which complement activation pathway can act as an amplification loop?
alternative b/c it is initiated by the binding of C3b
Which complement activation pathway has a role in both innate and adaptive immunity?
classical pathway (but can act in the absence of adaptive immunity, too)
How is the alternative pathway initiated?
spontaneous hydrolysis of C3
T/F. C6, 7, 8, and 9 are involved in inflammation, opsonization, and the assembly of the membrane-attack complex.
F. only assembly of the membrane attack complex
How is the activation of C1 prevented?
serpin (serine protease inhibitor)
What is the inheritance pattern of paroxysmal nocturnal hemoglobinuria, and what does it involve?
X-linked; problem with CD59 and DAF (decay accelerating factor); problem with complement-mediated destruction of RBCs
T/F. Cytokines are a subset of chemokines.
F. other way around
What is the difference between CC chemokines and CXC chemokines?
CC – 2 adjacent cysteines near the amino terminus; CXC – 2 cysteines separated by a single AA
Weibel-Palade bodies in the endothelial cells contain what?
preformed P-selectin
(Selectins/ICAMs) act first in the recruitment of leukocytes.
Selectins
(P/E/L) selectin first appears on endothelial cells following inflammation.
P, then E a few hours later
CXCL8 is released by _____ and recruits _____.
released by macrophages; recruits neutrophils
CCL2 recruits what?
monocytes
TNF-alpha does what?
vasodilation; disseminated intravascular coagulation
Which factors are responsible for increasing body temperature?
TNF-alpha, IL1-beta; IL-6
T/F. Interferon-alpha, beta, and gamma are induced by viral infection.
F. alpha and beta are, but gamma is produced later
Interferon synthesis occurs in response to what?
Double-stranded RNA
How do interferons inhibit viral replication
degrade viral RNA; inhibit protein synthesis; increase MHC class I molecules
T/F. NK cells develop from the common myeloid progenitor cell.
F. common lymphoid progenitor cell
What activates NK cells?
Interferon-alpha, beta, or IL-12
NK cells kill other cells bearing low levels of what?
MHC class I molecules
T/F. Like alpha:beta T cells, gamma:delta T cells recognize antigen as peptides presented by MHC molecules.
F. recognize antigens directly
T/F. B and T cells are involved with a adaptive immunity only.
F. intraepithelial gamma:delta T cells and B-1 cells and NK T cells
T/F. T cell receptors recognize antigen directly.
F. recognize antigen bound to MHC molecules on the surfaces of other cells
IgG antibodies consist of __ heavy and __ light chains. The heavy chains are linked together by ___. The light chains are linked to heavy chains by ___.
2 heavy, 2 light; heavy to light by disulfide bond; heavy to heavy by disulfide bond
What are types of light chains?
lambda and kappa (kappa twice as frequent as lambda)
What class of Ig is most abundant?
G
T/F. The light chain has a constant region.
T
An antibody cleaved by papin results in what?
two antigen-binding fragments (Fab); one Fc (Fragment crystallizable) domain
An antibody cleaved by pepsin results in what?
F(ab')2 fragment (2 antigen-binding arms remain linked)
What are haptens?
small molecules; recognized by antibody but able to stimulate anti-hapten antibodies only when linked to larger protein carrier
There are ___ hypervariable regions in both the heavy and light chains.
3: HV1, HV2, HV3
Combinatorial diversity in the context of Ig refers to what?
different combinations of heavy and light chain V regions & genes encoding V regions created from smaller segments of DNA
What is an epitope?
structure recognized by an antibody
T/F. T cells interact with pathogens and their toxic products in the extracellular spaces of the body.
F. Immunoglobulins do; T cells recognize foreign antigens that are displayed on the surfaces of the body's own cells
What does the T cell receptor consist of?
T cell receptor alpha and beta chains linked by a disulfide bond (minority are gamma-delta)
T/F. T cells respond to discontinuous amino acid sequences in proteins.
F. short contiguous sequences
MHC class (I/II) present peptides from viruses.
class I
MHC class II are normally found on what?
B lymphocytes, dendritic cells, and macrophages and not on other tissue cells
When CD4 T cells recognize peptides bound to MHC class II molecules on B cells, what happens?
stimulate B cells to produce antibody
When CD4 T cells recognize peptides bound to MHC class II molecules on macrophages, what happens?
activate these cells to destroy pathogens in their vesicles
The ends of the peptide-binding cleft are more open in MHC class (I/II) molecules.
more open in MHC class II molecules
MHC class I molecules bind what?
short peptides of 8-10 AA by both ends
T/F. The length of peptides bound by MHC class II molecules is constrained to 8-10 AA's.
F. not constrained; at least 13 Aas (typically 13-17 Aas)
T/F. Somatic hypermutation occurs in both B and T cells.
F. B cells only
T/F. The light chain contains V, D, and J.
F. only V and J
What is the order of joining V, D, and J for the heavy chain?
DJ is present before V comes
T/F. The heavy chain contains V, D, and J.
T
Kappa and lambda in the context of Ig refer to what?
types of light chain
What does the recombination signal sequence consist of?
heptamer, spacer, and nonamer
What is the 12/23 rule?
gene segment flanked by an recombination signal sequence with a 12-bp spacer can be joined only to one flanked by a 23-bp spacer RSS
What prevents V segments from joining to each other?
The 12/23 rule
Which enzymes are involved in VDJ recombination?
RAG 1 and 2
What are sources of diversity in V regions?
combinatorial diversity; junctional diversity (addition and subtraction of nucleotides); combinations of heavy and light (also called combinatorial); somatic hypermutation
(Heavy/light) chain gene arrangement occurs first.
heavy
There are 3 hypervariable loops in the protein chains of immunoglobins. Where are they with respect to V, D, and J?
2 are in V region; 1 in D (for heavy chain); between V and J for light chain
What is the difference between P and N nucleotides in the context of junctions between gene segments?
P – palindromic; N – nontemplate-encoded
When does somatic hypermutation occur?
when B cells respond to antigen along with signals from activated T cells
T-cell receptor gene rearrangement takes place where?
thymus
T/F. The T cell receptors alpha and beta contain V, D, and J.
only beta does; alpha contains only v and j
T/F. CDRs 1, 2, and 3 of TCRs contact the peptide bound in the MHC.
F. only CDR3
T/F. T cells undergo somatic hypermutation.
F. only B cells do
naïve B cells have ig (M, D, G, E, A) on their surface.
both M and D
What is the difference in structure between a secreted and a membrane-bound form of immunoglobulin?
Membrane-bound form, the Ig heavy chain has a hydrophobic transmembrane domain of 25 AA at the carboxy terminus
Which Ig forms pentamers in serum?
IgM
Which Ig can occur as either a monomer or a dimer?
IgA
T/F. B cells expressing IgM and IgD on their surface have undergone isotype switching.
F. have not undergone
The Fc receptors on macrophages and neutrophils recognize what?
IgG
The Fc portion of what binds to receptors on mast cells, basophils, and activated eosinophils?
IgE
Which Ig is secreted in mucous secretions, tears, and milk?
IgA
Which Ig is transferred into the fetal blood from the pregnant mother?
igG
Which Ig is found as a pentamer (or hexamer) in plasma?
IgM
Which Ig is found as a dimer?
IgA
T/F. IgM can be made after somatic hypermutation.
F. made before
What is the difference between allotype and idiotype?
Allotype – alleic variant of C region; Idiotype – different V regions
Peptides from the cytosol are bound to MHC class (I/II) and are recognized by CD (4/8) T cells. Peptides generated by intracellular vesicles are bound to MHC class (I/II) and are recognized by CD(4/8) T cells.
Cytosol – MHC class I – CD8; vesicle – MHC class II – CD4
What is the difference between what Th1 and Th2 cells do?
Th1 – activate macrophages to kill intravesicular pathogens; Th2 – activate B cells to make antibody
What protein transports peptides into the endoplasmic reticulum for MHC class I to present?
TAP 1 & 2 (transporters associated with antigen processing)
Peptides are generated in the (cytosol/ER) for MHC class I.
cytosol
Peptides are generated by what for presentation by MHC class I.
proteasome
The mycobacteria that cause leprosy and tuberculosis reside where? Their proteins are presented by MHC class (I/II).
intracellular vesicles of macrophages; proteins presented by MHC class II
Proteins that bind to surface immunoglobulins on B cells are presented by MHC class (I/II)
II
How are MHC class II moelcules prevented from binding peptides in the ER?
invariant chain
The MHC is located on which chromosome in humans?
6
What are MHC genes in humans called?
Human Leukocyte Antigen (HLA)
T/F. Cells express 1 MHC class 1 and 1 MHC class 2 proteins on their surfaces.
F. 3 (or 6) different class I and 3-4 (6 or 8) different class II
What are two methods that T cell receptors mediate transplant rejection?
Peptide-dominant binding & MHC-dominant binding
What are superantigens?
proteins that are recognized by T cells without being processed into peptides
Where do superantigens bind?
outside surface of an MHC class II molecule that has already bound peptide
Superantigens stimulate what?
CD4 T cells; secrete tons of cytokines
What is the first step in response to antigen
receptor clustering
What class of intracellular signal molecule does clustering of antigen receptors lead to?
protein tyrosine kinases
What are the three classes of amino acids that can be phosphorylated?
tyrosine, serine/threonine, histidine
How is signaling from the B-cell receptor complex transferred across the membrane?
Ig-alpha & Ig-beta; ITAMs (immunoreceptor tyrosine-based activation motifs)
The T cell (alpha/beta) chain is rearranged first.
beta
B lineage cells move toward the (central/peripheral) axis of the bone marrow cavity as they mature.
move toward central
What occurs during the pro-B cell stage?
DJ in early pro-B cell stage; VDJ in the late pro-B cell stage
What does the pre-B cell receptor consist of?
m chain with surrogate light chain (intracellularly, mainly)
Put in order: (immature/large pre/pro/small pre) B cells.
pro; large pre; small pre; immature
What occurs during the small pre-B cell stage?
light chain rearrangement
Immature thymocytes are found in the (cortex/medulla); mature thymocytes are found in the (cortex/medulla).
Immature – cortex; mature – medulla
What is the similarity between DiGeorge's syndrome and mice with the nude mutation?
both lack thymus
When is the rate of T cell production greatest?
before puberty
T/F. The production of new T cells stops at some point.
F. continues throughout life, but slower
T/F. T cell receptor genes are rearranged after they get to the thymus.
T
What does the pre-T cell receptor consist of?
beta chains paired with a surrogate pre-T cell receptor alpha chain
Does alpha chain rearrangement in T cells occur before or after double-positive thymocyte stage?
after double-positive
The (kappa/lambda) light chain is rearranged first.
kappa
T/F. Cells with only 1 antigen specificity are generated by one pre-B cell.
F. many antigen specificities; large pre-B cells (with surrogate light chain) divides many times before light chain recombines
What is the ratio of kappa to lambda light chains in humans/
2:1; kappa rearranged first
The (alpha/beta) chains of T cells rearranges first.
beta (VDJ)
T/F. A single alpha chain in a T cell can be paired with many different beta chains.
F. other way around. Single beta chain can be paired with many different alpha chains (beta rearranges first)
What occurs during the double negative phase of T cell rearrangemnet?
DJ and VDJ of beta chain
What occurs during the double positive phase of T cell rearrangement?
VJ of alpha chain
Alpha:beta and gamma:delta refer to what?
T cell receptors
Cells that fail to recognize the MHC molecules on the thymic epithelium never progress further than which stage?
Double-positive stage
Positive and negative selection refer to (B/T) cells.
T cells in the thymus
In the white pulp of the spleen (B/T) cells are clustered aroudn the central arteriole.
T cells; B cell areas are located farther out
Follicular dendritic cells (are/are not) leukocytes; (are/are not) phagocytic; (do/do not) express MHC class II proteins.
not leukocytes; not phagocytic; do not express MHC class II
How do follicular dendritic cells express antigen?
capture in the form of immune complexes (complex of antigen, antibody, complement); remain on surface
The Reed-Sternberg cell of Hodgkin's disease is a (B/T) cell.
B cell
What is a naïve T cell?
mature recirculating T cells that have not yet encountered their specific antigens
What are dendritic cells?
Antigen-presenting cells that ingest and present antigen to T cells
Macrophages display MHC class (I/II) molecules.
II
Cytotoxic T cells are MHC class (I/II).
I
Th1 and Th2 are CD (4/8) cells.
CD4
What is the difference between Th1 and Th2 cells?
Th1 – pathogens inside macrophage & dendritic cell vesicles stimulate; Th2 – extracellular antigens stimulate
Th(1/2) cells induce B cells to make IgG antibodies.
Th1
(CD8/Th1/Th2) activate the microbicidal properties of macrophages.
Th1
(CD8/Th1/Th2) activate B cells to produce IgM antibodies.
both Th1 and Th2
(CD8/Th1/Th2) cells stimulate production of different isotypes of Ig, including A & E.
Th2
What are the only cells that express both classes of MHC as well as the co-stimulatory cell-surface molecule?
dendritic cells, macropahges, and B cells
Where is antigen presented to naïve T cells?
peripheral lymphoid tissues (dendritic cells travel)
What are the most potent antigen-presenting cells for naïve T cells
dendritic cells
(L/P/E) selecin is expressed on leukocytes. (L/P/E) selectin is expressed on vascular endothelium.
L – leukocytes; P, E on vascular endothelium
In addition to antigen-specific receptor and CD4 or 8 co-receptor binding, what else is necessary to trigger T cells into action/
Co-stimulatory signal
How is a state of anergy for T cells created?
antigen binding to the T cell receptor in the absence of co-stimulation; (anergy – T cell becomes refractory to activation by specific antigen even presented by APC)
What is a B7 molecule?
Co-stimulatory molecule necessary for T cell activation
What are Langerhans' cells of the skin?
immature dendritic cells
After a macrophage ingests an organism, it presents its peptides on MHC class (I/II) molecules.
class II
The proliferation and differentiation of T cells is driven by which IL?
IL2 (Hot T-Bone stEAk)
How do cyclosporin A and FK506 (tacrlimus) suppress adaptive immune responses?
inhibit IL2 production
How does rapamycin (sirolimus) work?
inhibit signaling through the IL2 receptor
What is the difference between a naïve T cell and an armed effector T cell in the context of encountering its specific antigen?
no need for co-stimulation for armed effector T cell
When does a CD4 T cell decide whether to be a Th1 or Th2 cell?
after encounter with antigen
Th(1/2) leads to cell-mediated immunity and production of opsonizing antibodies (IgG); Th(1/2) leads to humoral immunity, especially IgM, IgA, and IgE.
Th1 – cell-mediated immunity; Th2 – humoral immunity
A Th(1/2) mediated immunity in the context of leprosy is a disaster.
Th2 – disaster b/c antibodies produced cannot reach intracellular bacteria
The main cytokine released by CD8 effector T cells is what? What can it do?
IFN-gamma; block viral replication or lead to the elimination of virus from infected cells without killing them
What happens to the DNA of cells undergoing apoptosis?
fragmentation of nuclear DNA into 200-BP pieces by nucleases that cleave between nucleosomes
What cytotoxic proteins are in the lytic granules of CD8 (cytotoxic) T cells?
perforin, granzymes, & granulysin
Mycobacteria can be eliminated when the macrophage is activated by a (CD8/Th1/Th2) T cell.
Th1
Macrophage activation is the principal effector action of (CD8/Th1/Th2) cells.
Th1
How is PCP pneumonia addressed by T cells?
activation of macrophages by Th1 cells; cause of death in AIDS b/c deficiency of CD4 T cells
What is the most characteristic cytokine produced by armed Th1 cells on interacting with their specific target cells?
IFN-gamma
Why are Th2 cells inefficient macrophage activators?
produce IL-10 (deactivate macrophages); do not produce IFN-gamma
Helper T cells that triger B cell activation into plasma cells are what?
Th2 class of CD4 cells (also Th1 T cells, but a lesser extent)
How can antibodies lead to the phagocytosis of pathogens?
recognized by Fc receptors on phagocytic cells; complemenet system
What leads to somatic hypermutation and isotype switching?
interaction of B cells with helper T cells
B cells present antigen in MHC class (I/II)-bound molecules.
II
T/F. All B-cell responses require armed peptide-specific helper T cells.
F. many microbial constituents, such as bacterial polysaccharides, can induce antibody production in the absence of helper T cells
What happens to the CD4 T cell before it activates the B cell.
interact with antigen-presenting dendritic cell or macrophage to becomes armed helper T cell
T/F. The B cell that a T helper cell activates produces antibodies to the same protein that the T cell recognizes a part of.
F. can be different
What are haptens?
small chemical groups that cannot elicit antibody responses on their own ; when coupled to a carrier protein, they become immunogenic
Which cytokines made by armed effector T cells are responsible for activating B cells?
CD40 ligand & IL4
What is the most abundant Ig in plasma?
IgG
Where do proliferating B cells go?
germinal center
Where does somatic hypermutation and isotype switching occur?
germinal center
What types of DNA changes does somatic hypermutation involve?
single bp changes (1/1000 per cell division)
Where do plasma cells produce antibody?
after becoming plasma cell, it moves to the bone marrow
T/F. Antibodies cannot be produced without isotype switching.
F. IgM antibodies produced before isotype switching
Which class of Ig is bound avidly by receptors on mast cells?
IgE
Where are the principal sites of IgA synthesis and secretion?
gut, respiratory epithelium, lactating breast, salivary & tear blands
Which Ig are transferred from mother to baby?
IgA in breast milk; IgG across plaenta
What is passive immunization?
transfer of antibodies directly to protect against a toxin
Antibodies initiate complement activation by which pathway?
classical pathway
Which Ig can initiate the classical complement activation pathway?
IgM & IgG
Which component of the complement cascade binds to the Fc region of IgM or IgG bound to a pathogen?
C1q
Cells with viral proteins on their surface bound by antibodies are destroyed by what?
NK cells
What causes inflammation?
activation of resident macrophages; secretion of cytokines and chemokines (esp. TNF-alpha); activation of complement
CD4 T cells stimulated in the presence of IL-12 and IFN-gamma tend to develop into Th(1/2) cells. Why
Th1; IFN-gamma inhibits the proliferation fo Th2 cells
CD4 T cells activated in the presence of IL-4 and IL-6 tend to differentiate into Th(1/2) cells.
Th2; IL-4 inhibit the generation of Th1 cells
What is the difference between Th1 and Th2 T cells?
Th1 – activate macrophages; Th2 – activate B cells
IL-10, a product of Th(1/2) cells, can inhibit development of Th(1/2) cells.
product of Th2; inhibit development of Th1
IFN-gamma, a product of Th(1/2), can inhibit development of Th(1/2) cells.
product of Th1; prevent activation of Th2
Large amounts of peptide that achieve a high density on the surface of antigen-presenting cells tend to stimulate a Th(1/2) response; low density elicits a Th(1/2) response.
High – Th1; Low – Th2
What are examples of pathogens that evade complete clearance and persist for the life of the host?
Leishmania, Toxoplasma, and herpes viruses
The dominant antibody isotype of the mucosal immune system is Ig what?
IgA
T/F. In blood, IgA is found as a dimer.
monomer in blood. Dimer in mucosal secretions.
What are M cells?
specialized epithelial cells in Peyer's patches (small intestine) with microfolds on their lumenal surface
What are Th3 T cells? What do they do? What do they secrete?
regulatory T cells; actively suppress antigen-specific responses; produce IL-4, IL-10, TGF-beta
Which IL's maintain memory T cells?
IL7 (in general); IL15 for CD8 T cells
Maximal levels of memory T cells occur how long after an infection? Memory B cells?
T – 5 days; B – 1 month
T/F. T cell receptors undergo somatic hypermutation.
F. do not
How can the response of an Rh- mother be prevented when she has an Rh+ child? Will it work when she has memory B cells to the Rh antigen?
Anti-Rh antibody given to the mother before her reaction; not work if already has memory B cells b/c more sensitive and higher affinity
What is the difference between antigenic drift and antigenic shift in the context of influenza?
Drift – point mutations in genes encoding hemagglutinin & neuraminidase; shift – reassortment of segmented RNA genome & related animal influenza viruses
How does trypanosomes escape the immune system and cause sleeping sickness?
changes in major surface anitgen occurs repeatedly within a single infected host
Why is it difficult for CD8 T cells to respond to viral infections in neurons?
neurons carry very low levels of MHC class I molecules (helps b/c neurons do not regenerate or regenerate slowly)
How does toxoplasma make itself invisible to the immune system?
generate its own vesicle
Which is worse: tuberculoid or lepromatous leprosy?
lepromatous worse: cell-mediated immunity profoundly depressed
Increased risk of infection by pyogenic bacteria can be caused by what?
deficiency of antibody, complement, or phagocytic function
What is special about pyogenic bacteria that allows their escape from macrophage sand neutrophils?
have polysaccharide capsules
What gene is defective in Bruton's X-linked agammaglobulinemia and how is disease caused?
Bruton's tyrosine kinase; lead to arrest at the pre-B-cell stage
When do infants start to produce IgG?
6-12 months of age
Defects in the membrane-attack components results exclusively in suscewptibility to what?
Neisseria species
What's wrong in chronic granulomatous disease?
phagocytes cannot produce superoxide radical (NADPH oxidase system)
What's wrong in Chediak-Higashi syndromein the context of immunodefiiency? What is the clinical presentation of this disease?
problem with vesicle formation; cannot fuse lysosomes with phagosomes; partial albinism, abnormal platelet function
Severe combined immunodeficiency is associated with what defect?
T cell defects
What's wrong in DiGeorge's syndrome?
thymic epithelium fails to develop normally
Epstein Barr virus infects what cells?
B cells
Why do people with epstein-barr virus infections not develop cancer usually?
actively controlled by cytotoxic T cells
Surgical removal of the spleen is associated with a lifelong predisposition to overwhelming infection by what?
Strep. Pneumoniae
What cells do HIV infect?
CD4 T cells, dendritic cells, and macrophages
What component of the HIV virus binds to CD4?
gp120
What are the two major co-receptors for the HIV virus?
CCR5 and CXCR4 (on activated T cells)
What component of the HIV virus causes fusion of the viral envelope to the plasma membrane?
gp41
Infection of CD4 T cells via _____ occurs early in the course of infection; late in infection, infection occurs via _____ .
Early – CCR5; Late – CXCR4
What characterizes a lentivirus?
Lenti – slow; slow replication
What is the half-life of the HIV virus in productively infected cells?
2 days
What are early infections when the CD4 T cell count is low in AIDS?
Candida & Tuberculosis
What are late infections when the CD4 T cell count is low in AIDS?
varicella zoster, B-cell lymphomas; Kaposi's sarcoma
What are the infections in the final stages of AIDS infection?
Cytomegalovirus & M. avium complex
Allergy is caused by which Ig?
IgE
IgE is involved in protection against what?
parasitic worms
Which type of hypersensitivity is allergy?
Type I hypersensitivity
IgE binds to the surfaces of what cells?
mast cells
IgE antibody production requires Th(1/2) cells that produce which IL's?
Th2 cells; IL4 & 13
IgE antibody production can be inhibited by Th(1/2) cells that produce ___ .
Th1 cells; IGN-gamma
Which IL's favor development of a Th2 response?
4, 5, 9, 10, 13
Which factors favor a Th1 response?
IL-12, Th1
What is atopy?
exaggerated tendency to mount IgE responses to a wide variety of environmental allergens
IgE is fixed on the surfaces of what cells?
mast cells, basophils, eosinophils
Which IL causes increased production of eosinophils?
IL-5
Systemic anaphylaxis due to penicillin is due to which Ig?
IgE
In desensitization to allergy, what is the mechanism behind treatment?
shift antibody response away from one dominated by IgE toward one dominated by IgG
What are type II hypersensitivity reactions?
drug binds to cell surface and serves as a target for anti-drug IgG antibodies
What are type III hypersensitivity reactions?
deposition of antigen:antibody aggregates or immune complexes in particular tissues and sites
What is an Arthus reaction?
immune complex binds to leukocytes; local inflammatory response with increased vascular permeability; polymorphonuclear leukocytes to enter the site from local vessels
Serum sickness is an example of a type what hypersensitivity reaction? What is serum sickness? What is its timeframe?
III (3); injection of large quantities of a poorly catabolized foreign antigen; 7-10 days after injection b/c switch from IgM to IgG
What occurs in type 4 hypersensitivity reactions?
Delayed-type hypersensitivity; antigen-specific effector T cells (CD4 Th1 and CD8)
The tuberculin test is an example of which type of hypersensitivity?
4; delayed-type hypersensitivity
How does the immune system distinguish self ligands from nonself ligands?
encounter when lymphocyte is immature; high and constant concentration of ligand, binding in the absence of co-stimulatory signals
Antibodies against what are present in Graves' disease?
Thyroid-stimulating hormone
Antibodies against what are present in Hashimoto's thyroiditis?
thyroid peroxidase
What is epitope spreading?
antoimmunity to a single epitope can lead to more widespread autoimmunity
What are the immunologically privileged sites in the human?
brain, eye, testis, uterus
Which cytokines do Th1 cells secrete?
IGN-gamma and TNF-alpha
What are CD4 CD25 T cells?
regulatory T cell; suppresses immune response
Hashimoto's thyroiditis is a result to autoantibodies against what?
thyroid peroxidase and thyroglobulin
Graves' disease is an example of which type of hypersensitivity? What's the problem in this disease?
Type 2; antibody binding to thyroid stimulating hormone receptor; excessive production of thyroid hormone
Goodpasture's syndrome is an example of a type what hypersensitivity reaction? What's the problem?
Type 2; antibody against basement membrane collagen
In autoimmune diabetes mellitus, what causes damage to the insulin-secreting beta cells?
CD8 T cells
How long does it take for an allograft to be rejected? What about a second graft?
10-13 days; 6-8 days
One sibling in how many should be HLA-identical?
1 in 4
What are minor histocompatibility antigens?
polymorphisms in proteins inside the cells of different members of a species
What causes direct allorecognition in the context of tissue transplant?
donor antigen-presenting cells leaving the grafting and migrating to regional lymph nodes; activate host T cells
What causes indirect allorecognition in the context of tissue transplant?
uptake of allogeneic proteins by the recipient's own antigen-presenting cells and presentation to T cells
What causes hyperacute graft rejection?
preexisting alloantibodies
What is the half0life for functional survival of renal allografts?
8 years
How does the mixed lymphocyte reaction work?
lymphocytes from a potential donor are mixed with irradiated lymphocytes from the potential recipient; look for T cell division
In general, how to steroids work?
bind intracellular receptors that regulate transcription of specific genes
What are side effects of corticosteroids?
fluid retention, weight gain, diabetes, bone mineral loss, thinning of skin
What are the three cytotoxic drugs most commonly used as immunosuppresants/
azathioprine, cyclophosphamide, mycophenolate
How does azathioprine work?
block de novo synthesis of adenosine & guanosine monophosphate; inhibit DNA synthesis
How does cyclophosphamide work?
alkylates DNA (nitrogen mustard)
What are side effects of cyclophosphamide?
bladder: hemmorhage & neoplasia
How do cyclosporin and tacrolimus work?
inhibit calcineurin (phosphatase); reduce expression of IL-2
How does rapamycin work?
block signal transduction triggered by ligation of growth factor receptors; blocks proliferation of T cells
Regulatory T cells secrete what to downregulate the immune response?
IL-10 and TGF-beta
What is herceptin (trastuzumab)?
huanized monoclonal antibody that targets growth factor receptor; used in breast cancer
T/F. CD8 T cells are generated by inactivated viruses. Why/how?
F. not generated; inactivated viruses do not produce proteins in the cytosol, so cannot be presented by MHC class I molecules
IL-12 encourages a Th1(1/2) response.
Th1
What are Toll-like receptors important for?
Dorso-ventral patterning & host defense
What is the difference between jawed fish and jawless vertebrate fish in terms of immune system?
jawed fish can mount adaptive immune response; jawless cannot