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Beck - Immunology - Exam 2
Sepsis, Immunogens, Antigen Presentation and Recognition, Immunoglobin, and Lymphocyte Development
144
Immunology
Undergraduate 4
11/13/2012

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Term
Septic Shock
Definition
systemic inflammation in response to blood-borne pathogens
Term
SIRS
Definition
Systemic Inflammatory Response Syndrome
systemic activation of the innate immune response, typically due to bacterial infections
Term
MOD
Definition
Multi-Organ Dysfunction Syndrome
altered organ function due to septic shock
Term
DIC
Definition
Disseminated Intravascular Coagulation
massive coagulation of microvessels
Term
How is severe septic shock treated?
Definition
with antibiotics and management of symptoms
Term
Two functions of Dendritic Cells
Definition
1. inducing tolerance
2. stimulating specific T and B-cells
Term
Affinity maturation
Definition
proliferation of Memory B cells in the germinal center and subsequent mutation of the antibody variable region
Term
Immunogen
Definition
antigens that are able to induce an immune response
Term
Antigen
Definition
molecules that are able to be recognized by the immune system
Term
Properties of an Immunogen
Definition
1. Foreign
2. High Molecular Weight
3. Chemically Complex
4. Presentable
Term
Carrier
Definition
an immunogen that binds with an antigen to initiate an immune response to that antigen
Term
Hapten
Definition
an antigen that can now be recognized by the immune system since it is bound to a carrier
Term
Which biomolecules are presentable?
Definition
1. Carbohydrates (hapten)
2. Lipids (on CD1)
3. Nucleic Acids (hapten)
4. Proteins
Term
Epitope
Definition
region of antigen recognized by an antibody
Term
Linear epitopes
Definition
fragments of protein
Term
Conformational epitopes
Definition
found in folded proteins and are only recognizable by B-cells
Term
Cross-reactivity
Definition
response to the same epitope on different proteins
Term
Cross-protection
Definition
ability to respond to new proteins through cross-reactivity
Term
MHC I
Definition
presents intracellular peptide antigens
Term
MHC II
Definition
presents phagocytosed peptide fragments
Term
Compare MHC I and MHC II
Definition
MHC I: narrow pocket (8-10 aa); bonds to CD8; one transmembrane protein; cytoplasmic peptides
MHC II: open-ended pocket (13-17 aa); bonds to CD4; two transmembrane proteins; phagocytosed peptides
Term
CD1
Definition
MHC of gammma:delta T cells
presents glycolipids (deeper pocket)
Term
Calnexin
Definition
holds alpha-MHC Class I protein in place in the ER
Term
Calreticulin
Definition
holds the empty MHC Class I protein in the ER
Term
Tapasin
Definition
binds to MHC Class I in the ER to bring it near to the TAP complex
Term
TAP complex
Definition
complex of proteins that takes cytoplasmic peptides and secretes them into the ER
Term
ERAAP
Definition
cleaves proteins and assists with MHC Class I binding
Term
Cellular proteosome
Definition
protein eating machine that completely degrades faulty proteins
Term
Immunoproteosome
Definition
Following exposure to interferons, the cellular proteosome becomes more active and leaky for better presentation of peptides by MHC Class I
Term
Three methods of viral evasion of MHC Class I
Definition
1. Block TAP complex
2. Inhibit MHC Class I loading
3. Degradation of MHC Class I
Term
Two functions of Invariant Chain
Definition
1. Prevention of peptide binding to MHC Class II in the ER
2. Targeting of MHC Class II to acidic endosomes
Term
CLIP
Definition
Class II Invariant Chain Peptide
Remnant of invariant chain that remains weakly bound to the antigen binding pocket of MHC Class II after acidification
Term
HLA-DM
Definition
prevents MHC Class II from binding weakly to proteins, including CLIP
Term
HLA-DO
Definition
interferes with HLA-DM and prevents naive B cells from expressing MHC Class II antigens until exposure to INF-gamma
Term
Two key features of MHC-antigen complex
Definition
1. Stability
2. Rapid removal of empty MHC
Term
MHC
Definition
Major histocompatibility complex
Term
HLA
Definition
human leukocyte antigen
Term
Polygeny
Definition
multiple copies of genes are present
Term
Polymorphism
Definition
espression of multiple alleles
Term
HLA-G
Definition
replaces MHC Class I in placenta and inhibits NK cell killing of placental cells
Term
HLA or MHC haplotype
Definition
particular combination of HLA alleles in an individual
Term
HLA-E
Definition
presents MHC Class I
Term
Superantigens
Definition
stabilize the interaction between the TCR and MHC resulting in tremendous levels of T-cell activation
Term
Humoral immunity
Definition
immunity mediated by antibodies
Term
Antibody
Definition
protein in the serum that combines specifically with an antigen
Term
Immunoglobins
Definition
antibodies
Term
B-cell Receptor
Definition
membrane bound antibodies/immunoglobulins
Term
Five functions of antibodies
Definition
1. Neutralization
2. Agglutination
3. Complement activation
4. Opsonization
5. ADCC
Term
Light chain domains
Definition
1. variable domain (VL)
2. constant domain (CL)
Term
Heavy chain domains
Definition
1. variable domain (VH)
2. 3-4 constant domains (CH)
Term
Fab
Definition
antigen binding domain of an antibody

http://upload.wikimedia.org/wikipedia/commons/thumb/e/e2/2fab_fc.svg/200px-2fab_fc.svg.png
Term
Fc
Definition
immune system interaction (communication) region of an antibody

http://upload.wikimedia.org/wikipedia/commons/thumb/e/e2/2fab_fc.svg/200px-2fab_fc.svg.png
Term
Antigen Binding Domain
Definition
combination of the VL and VH
Term
Immune System Interaction Region
Definition
occurs via the heavy chain
Term
Hypervariable region
Definition
variable region within the variable domains that are exposed to the antigen
Term
CDR
Definition
complementarity determining regions
hypervariable regions that determine the ability of the antibody to bind the antigen
Term
Five different classes of antibody
Definition
1. IgG
2. IgM
3. IgD
4. IgA
5. IgE
Term
Isotype
Definition
antibodies that differ in structure, but are identical in their variable region
Term
Idiotypes
Definition
antibodies of the same class, but with different variable regions
Term
Allotypic
Definition
antibodies produced from different alleles
Term
Heavy Chain Genes
Definition
mu, delta, gamma, epsilon, and alpha
Term
J chain
Definition
protein used to link IgA into dimers and IgM into pentamers
Term
How many subclasses of IgG are there?
Definition
four
Term
IgG
Definition
four subclasses
most abundant antibody class
classical pathway of complement activation
only antibody transported across placenta
Term
IgG4
Definition
makes a bivalent antibody
Term
IgA
Definition
second most abundant
present in mucous and secretions
monomer, dimer or trimer
two subclasses
alternate pathway of complement activation
Term
How many subclasses of IgA are there?
Definition
two
Term
sIgA
Definition
dimeric IgA that binds to a secretory peptide
Term
secretory component
Definition
protein that bind sto dimeric IgA and allows it to be secreted thru the mucousal epithelium
Term
IgM
Definition
first response antibodies
largest, pentamer
stimulate macrophages
classical pathway of complement activation
Term
IgD
Definition
bound to B-cell membranes
Term
IgE
Definition
bound to mast cells and basophils
involved in allergic-type reactions
Term
ADCC
Definition
antibody dependent cell cytotoxicity
Term
Opsonization
Definition
coating of the pathogen with antigen
leads to clearance of the pathogen by Fc and Complement receptors on phagocytic cells
Term
Seven Purposes of Fc Receptors
Definition
1. Promotion of phagocytosis
2. Activation of phagosome
3. Promotion of cell killing (ADCC)
4. Activation of the immune cell (esp. NK cells)
5. Antibody level regulation
6. Degranulation of mast cells
7. Antibody transport
Term
Gamma globulin
Definition
pooled IgG from thousands of individuals
Term
Two forms of artificial passive immunity
Definition
1. Pooled IgG
2. Specific IgG
Term
Bone marrow
Definition
site of pre-B cell maturation
Term
Ssites of pre-T-cell maturation
Definition
thymus and intestinal cryptopatches
Term
Stromal cell
Definition
stimulates pre-lymphocyte to stay alive and rearrange the BCR/TCR genes
Term
RAG 1/2
Definition
first genes expressed in the rearrangement process
Term
Heavy chain genes are composed of what regions?
Definition
V, D and J
Term
Light chain genes are composed of what regions?
Definition
V and J
Term
Antibody diversity theories
Definition
1. germ line theory
2 somatic mutation theory
Term
V(D)J recombinase
Definition
RAG complex
binds to RSSs and loops out DNA and brings two joining regions in proximity to one another
Term
RSSs
Definition
Recombination Signal Sequences
sites of RAG complex binding and DNA cleavage
Term
DNA-PK
Definition
DNA-Dependent Protein Kinase
cuts a strand one or two bases from its end and unfolds it, leaving a small overhang for joining between the two strands
Term
TDt
Definition
terminal deoxynucleotidyl transferase
attaches additional bases to both pieces of DNA until there is a match between them
Term
Steps in the process of recombination
Definition
1. V(D)J recombinase binds to RSSs and loops out DNA
2. DNA is cleaved at RSSs
3. 3'OH attacks the second strand, cleaving the DNA
4. DNA-PK cuts and unfolds strands
5. TDt attaches bases until a match is made
6. Non-matching nucleotide overhangs are cleaved off
Term
P-nucleotides
Definition
Palindromic nucleotides
derived from hairpins
Term
N-nucleotides
Definition
random nucleotides
added by TDt
Term
Combinatorial diversity
Definition
due to different possible combinations of variable regions
Term
Junctional diversity
Definition
due to differences between N-nucleotides
Term
Steps of TCR Rearrangement
Definition
1. D-J rearrangement
2. V-DJ rearrangement
3. Verification of Function
4. Proliferation
5. Rearrangement of light chain
6. MHC Class Selection
7. Negative Selection
Term
Allelic exclusion
Definition
process where only one allele is recombined at a time
none on TCR alpha or gamma
Term
Negative selection
Definition
too much signalling from a lymphocyte results in apoptosis
Term
B220
Definition
CD45R
first surface marker of B-cell development
Term
CD45
Definition
B220
first surface marker of B-cell development
Term
Main B-cell stages
Definition
1. Pro-B cell
2. Pre-B cell
3. Immature B cell
4. Transitional B cell
5. Mature B cell
6. Anergic B cell
Term
B-1 B cell
Definition
CD5+ B cell found in the peritoneum that produces a lot of IgM and is T-cell independent
Term
Pro-B cell
Definition
in the process of rearranging the heavy chain
Term
Pre-B cell
Definition
expresses the heavy chain with a surrogate light chain and is in the process of rearranging the light chain
Term
Immature B cell
Definition
expresses only IgM and undergoes negative selection
Term
Transitional B cell
Definition
short-lived cell that has left the bone marrow but not yet arrived in the lymphoid tissue
Term
Mature B cell
Definition
Naive B cell
can be activated by T cells and expresses both IgM and IgD
Term
Anergic B cell
Definition
naive B cell that was inactivated by a dendritic cell and T cell
Term
Marginal Zone B cell
Definition
CD1+ B cell that recognizes lipid antigens and promotes clearance of immunogenic self antigens
Term
Major Steps of B-cell Development
Definition
1. Pro-B cell expresses RAG 1/2
2. Rearrangement of heavy chain
3. Proliferation of Pre-B cell
4. Recombination of the light chain
5. Immature B cell
6. Bone marrow screening
7. Transitional B-cell
8. Mature/Naive B-cell
Term
The substitute light chain is composed of what two proteins?
Definition
lambda5 and VpreB
Term
What are the proteins that make up the pre-BCR?
Definition
Heavy chain, lambda5, VpreB, Ig alpha, and Ig beta
Term
Order of light chain recombination
Definition
try each kappa light chain gene (one maternal or paternal gene), then lambda light chain genes
Term
Receptor editing
Definition
further rearrangement of the light chain to make a BCR that is not auto-reactive
Term
Ignorant B-cells
Definition
slightly autoreactive B-cells that do not bind tightly enough to host antigens to induce anergy, but are never activated by T-cells
Term
Thymocytes
Definition
multipotent stem cells in the thymus that can develop into T-cells or NK cells
Term
Major steps of T-cell development
Definition
1. Stem cells enter the cortex of the thymus
2. Nurse cells induce them to become CD44+ DN thymocytes (DN1)
3. CD44- DN thymocytes (DN2) rearrange TCR beta and become commmited T-cells
4. CD44- pre-TCR+ DN thymocytes express pre-TCR
5. CD44- double positive thymocytes express pre-TCR and CD4 and CD8
6. Rearrangement of both TCR alpha genes
7. Positive selection of a TCR
8. Single positive thymocytes screened for interaction w/ MHC I or II and become CD8+ or CD4+
9. Negative selection
3.
Term
Thymic stroma
Definition
thymic 'nurse' cells'
induce thymic lymphoblasts to become DN1 thymocytes
Term
DN1
Definition
CD44+ double negative thymocytes
Term
DN2
Definition
CD44- double negative thymocytes
Term
DN3
Definition
pre-TCR expression
Term
DN4
Definition
proliferation before rearrangement of TCR-alpha
Term
Pre-TCR
Definition
expresses the TCRbeta and pTalpha which allows for the testing of the TCRbeta rearrangement
Term
Positive selection
Definition
screens for TCRs that can interact with MHC Class I or MHC Class II
Term
Negative selection
Definition
screens for TCRs that interact with host antigen displayed by antigen presenting cells in the thymus
Term
Cortical epithelial cells
Definition
antigen presenting cells that express both MHC Classes with a variety of self peptides to drive positive selection
Term
In which region of the thymus do dendritic cells reside?
Definition
the junction of the cortex and medulla
Term
AIRE
Definition
autoimmune regulator gene that is important for the expression of non-thymic genes in the thymus
Term
Hassal's corpuscle
Definition
contain degenerating epithelial cells rich in cytokeratins
Term
Regulatory T-cells
Definition
CD4+ CD25+ autoreactive T-cells that inhibit TE cell responses in the periphery
Term
gamma:delta t-cells
Definition
invariable T-cells present in fetuses
Term
tolerance
Definition
the lack of an immune response to self-antigens
Term
autoimmune polyglandular syndrome
Definition
autoimmune disease affecting multiple glands resulting in reduced thyroid function
Term
rheumatoid factor
Definition
antibodies to self IgG that are sometimes developed because there is so much IgG present in the body BCR is never cross-linked and inactivated
Term
immunologically priveleged sites
Definition
areas of the body that do not allow entry of immune cells
Term
sympathetic opthalmia
Definition
one eye is damaged and an immune response develops leading to an autoimmune response to the second eye
Term
Three features of immune priveleged sites
Definition
1. extracellular fluid is maintained separately
2. naive B and T cells are generally excluded
3. foreign antigens are bound to host factors that lead to very specific immune responses
Term
Th3 and Tr1 T cells
Definition
mucosal immune cells that are involved in tolerance to food and normal flora
Term
Steps of lymph node development
Definition
1. Recruitment of dendritic cells
2. DCs recruit T cells and B cells
3. B cells stimulate development of follicular DCs or M cells
4. FDCs recruit large quantities of B cells
5. local signals cause B and T cells to become tissue specific
Term
Four groups of antigen presenting cells
Definition
1. monocytes
2. dendritic cells
3. lymphocytes
4. facultative APCs
Term
Monocytes
Definition
also known as macrophages, Kupffer cells or microglial cells
found in blood and tissues, esp. lungs
Term
Dendritic cells
Definition
bone-marrow derived
found in tissues and lymphoid tissue
induce anergy and activation
express internalized antigen by both MHC I and II
Term
Lymphocytes as APCs
Definition
All B cells are phagocytic and some T cells can be stimulated to be so, too
Term
Facultative APCs
Definition
cells, such as eosinophils, that can be induced to become APCs under the right conditions
Term
Follicular Dendritic Cells
Definition
maintain antigen on the surface to upkeep the immune response in the lymph node
Term
Antigen maintenance in the lymph node
Definition
1. follicular dendritic cells: antibody bound antigen
2. marginal zone macrophages: hold sugar antigen
3. tissue DCs: maintain tissue antigen
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