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NSUCOM - Immunology Exam 1
From Dr. Davis's Notes
189
Immunology
Professional
01/20/2011

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Cards

Term
Humoral immunity involves which cells?
Definition
B cells and CD4+ TH2 cells
Term
Cell mediated immunity involves which cells?
Definition
CD4+ TH1 and CD8+
Term
Secretion of IFN upregulates what? What causes it’s secretion?
Definition
MHC Class I molecules and viral infections (respectively)
Term
What do cytokines upregulate?
Definition
MHC II. Those produced by CD4+ TH1 cells produce cytokines which active macrophages and upregulate the expression of Fc receptors on macrophages, NK cell and neutrophils. Cytokines recruit neutrophils and other leukocytes to the infected areas
Term
What does TLR4 recognize, stimulate, and do?
Definition
LPS, NF-κB, upregulates cytokine production and other molecules for B/T cell activation
Term
What amino acids comprise the hinge region?
Definition
Pro, Ser, Thr
Term
Where is the hinge region found, and what isotypes is it absent?
Definition
Between CH1 and CH2…not found in IgM or IgE
Term
Where does pepsin cleave an antibody?
Definition
Below the S-S bond at the hinge, producing 1 fragment (Fab)2
Term
What isotypes is the J chain associated with?
Definition
Polymeric → IgA and IgM (not hexameric IgM though)
Term
What is J chain required for?
Definition
Polymerization and interacts with poly-Ig receptor for transcytosis
Term
Which domains of the Ab do not interact?
Definition
CH2 due to steric hinderence of CHO
Term
Which part of the Ab makes contact with epitopes?
Definition
The hypervariable regions of the variable domain, AKA CDR’s (complement determining regions)
Term
Which isotypes have subclasses and how many?
Definition
IgG = 4 and IgA = 2
Term
Where is IgM found as a monomer?
Definition
As a BCR on mature B cells
Term
What isotype is the most efficient in activating the complement pathway?
Definition
IgM
Term
What is the only isotpye made by the fetus?
Definition
IgM until 4-6 months of age when they can make other Ig’s
Term
What is the primary structural characteristic used to determine the different subclass of IgG?
Definition
The hinge region
Term
Why does IgG have such a long half life?
Definition
Due to the recycling of it
Term
What is the only isotype able to cross the placental barrier?
Definition
IgG (IgG1>3>2>4)
Term
Which IgG subclasses activate complement?
Definition
1,2, and 3
Term
When does the production of IgG take place in an infant?
Definition
4-6 months of age
Term
When can IgG participate in ADCC?
Definition
When bound by Fc receptors on NK cells
Term
What is the best opsonin?
Definition
IgG1
Term
Which IgA subclass is predominate in serum?
Definition
Iga1 with ratio of 5:1
Term
Which IgA subclass is directed towards polysaccharide epitopes? Protein epitopes?
Definition
2 and 1
Term
Which Ig is the most abundant made? Which is the most abundant in tissues and serum?
Definition
IgA (>60% of the 3g of antibody made per day) and IgG respectively
Term
What is the most predominate isotype found in secretions and mucosal surfaces?
Definition
IgA
Term
What isotypes are found in gingival cervicular fluid?
Definition
Monomeric IgA, IgG and IgM
Term
Monomeric IgA is mostly found in …
Definition
serum
Term
Polymeric IgA is found…
Definition
In secretions in it’s dimer form (secretory component helps protect it from cleavage by enzymes)
Term
Where is secretory IgA mostly secreted from?
Definition
Minor and major salivary glands
Term
Where is IgE found?
Definition
Bound to surface of mast cells, basophils and eosinophils by its Fc(epsilon) receptor
Term
What does IgE do when it binds an antigen?
Definition
Degranulation releasing granules
Term
Which isotype plays a role in protection against parasites?
Definition
IgE by binding epitopes of the parasite and releasing granules to kill parasite directly
Term
What is the function of IgD?
Definition
B cell activation as a BCR
Term
What happens to a B cell is IgD is missing?
Definition
Self reactive B cells can enter lymphoid organ and proliferate
Term
Hematopoetic stem cells can become…
Definition
Stem cells, myeloid cells, lymphoid cells or erythroid cells
Term
Name some cells from the myeloid lineage
Definition
Monocytes/macrophages, dendritic cells, and granulocytes (basophil, eosinophil, mast cell, neutrophil)
Term
Name some cells from the lymphoid cell lineage
Definition
T cell, B cell, NK cell
Term
Name some cells from the erythroid lineage
Definition
Platelets and RBCs
Term
What surface receptors do monocytes/macrophages have?
Definition
CR3 – complement receptor 3 for Cb3
Fc – for Fc portion of IgG and IgE antibodies
Term
Macrophages can be activated from their resting state by:
Definition
PAMPs (LPS, mannose) Opsinization IFN-γ (produced by Th1, CD8+, and NK cells)
Term
What are the functions of macrophages?
Definition
Phagocytosis, antigen presenation, production of soluble mediators, and ADCC
Term
What cytokines does a macrophages secrete when it phagocytoses a pathogen?
Definition
IL-1, IL-6, and TNF-α
Term
When a target is coated with IgG, what do macrophages do?
Definition
Kill the target directly without phagocytosis via ADCC
Term
What is immunopathology?
Definition
The release of enzymes causing damage to nearby neighbors of infected cells (“innocent bystanders”)
Term
What is the best phagocyte we have?
Definition
Neutrophils
Term
What is the functions of neutrophils?
Definition
Phagocytosis and cytokine production
Term
What are defensins and what cells secrete these?
Definition
Defensins poke holes in membranes to kill phagocytosed pathogens. Neutrophils release these.
Term
What cells have an oxidative burst?
Definition
Neutrophils and macrophages
Term
What cytokines do neutrophils produce?
Definition
Proinflammatory cytokines – IL-1, IL-6, TNF-α, and IL-8 (IL-8 is the only additional one it secretes vs. macrocrphages)
Term
what cytokines do dendritic cells produce?
Definition
IL-1β, IL-12 and TNF-α
Term
what are the functions of dendritic cells?
Definition
phagocytosis, antigen presentation, negative selection (where they present self antigens to developing T cells in thymus), and cytokine production
Term
where are follicular dendritic cells found?
Definition
germinal cetners and follicles of lymphoid tissues
Term
T or F: Follicular dendritic cells are phagocytic
Definition
Flase, they are NOT phagocytic
Term
T or F: Dendritic cells present to T cells and Follicular Dendritic Cells present to B cells
Definition
True
Term
What is the function of FDC's?
Definition
They bind the whole antigen-antibody complex via the Fc portion of the antibody, and present the "unprocessed" antigen to B cells in lymphoid germinal centers
Term
T or F: FDCs express MHC molecules
Definition
False, they do not express MHC molecules
Term
CD4+ T cells differentiate into ____ who's effector function is to _______
Definition
T helper cells.
Produce cytokines
Term
CD8+ T cells differentiate into ______ whos effector function is to ____
Definition
T cytotoxic cells who kill infected host cells or tumor cells
Term
Are CD4 and CD8 expressed exclusively or mutually on T cells?
Definition
mutually
Term
what cytokines inhibit TH2 differentiation?
Definition
IFN-γ, produced by TH1 cells
Term
What cytokines prevent differentiation of TH1 cells?
Definition
IL-4 and IL-10 (produced by TH2 cells)
Term
Which cytokines favor TH1 differentiation?
Definition
IL-12 (produced by DCs, macrophages, and neutrophils)
Term
TH1 cells produce what cytokines?
Definition
IL-2, IFN-γ, and TNF-β
Term
TH1 cells stimulate which T cells?
Definition
CD8+
Term
TH1 cells stimulate isotype switching in B cells to produce which isotypes?
Definition
IgG2, IgG3, and IgA
Term
TH2 cells produce what cytokines?
Definition
IL-4, IL-5, IL-6, IL-10
Term
What cells do TH2 cells stimulate?
Definition
B cells to produce antibodies
Term
Which isotypes does TH2 cells stimulate B cells to produce?
Definition
IgG1, IgE, and IgA
Term
The presentation and severity of disease is determined by what?
Definition
the predominance of TH1 vs TH2 phenotypes
Term
What is the function of CD8+ T cells?
Definition
to kill target cells through release of cytotoxic enzymes such as host cells with intracellular pathogens, tumor cells or incompatible grafted/transplanted tissues
Term
Naive B cells have which BCRs present?
Definition
IgM and IgD
Term
CD40 is found where?
Definition
B cell surface
Term
CD40 interacts with _____ to _____.
Definition
CD40L on T cells to provide second activating signal for B cells and signals the B cell to undergo isotype switching
Term
CD80 or CD87 are found where?
Definition
B cell surface
Term
CD80/86 interact with _____ to _____.
Definition
CD28 on T cells to provide second activating signal for T cell
Term
What are the functions of B cells?
Definition
Production of antibodies (plasma cells), immunologic memory (memory B cells), antigen presentation (antigen binds to BCR and is phagocytosed and presented to T cell via MHC molecule)
Term
NK cells are part of (adaptive or innate) immune system
Definition
both
Term
how do we identify NK cells?
Definition
Fc-γ receptor and IL-2R receptor (receptor for IL-2 that proliferates at low levels of IL-2). Do NOT have TCR or BCR
Term
what is the function of NK cells?
Definition
direct killing of target cells by release of cytotoxic enzymes and production of IFN-γ
Term
IFN-γ has what functions?
Definition
antiviral effects (protects cell) and stimulates cytotoxic activity of Tc cells and macrophages
Term
NK kill via ADCC when...
Definition
Fc-γ receptors on surface bind IgG coated antigen
Term
Where is the site that blood-borne pathogens are processed and presented?
Definition
Spleen
Term
what ways can a antigen enter a lymph node?
Definition
via the lymph either as soluble antigen or within phagocyte
Term
what are M cells?
Definition
specialized mucosal epithelial cells that delivery pathogens across mucosa into MALT
Term
the majority of lymphocytes are found where?
Definition
lymphoid tissues
Term
what do naive T cells have that allows them to enter lymph nodes?
Definition
T selectin
Term
Once a T cell is activated in a lymph node, what happens?
Definition
it loses its L selectin receptors and will not reenter other lymph nodes, but leave the lymph node and reenter circulation to find tissues that are colonized by infectious microorganisms
Term
Where is the one place in the body where lymphocytes do not circulate through secondary lymphoid tissue in both blood and lymph?
Definition
the spleen
Term
What is psoriasin?
Definition
small fatty acid that has antibacterial and chemotactic properties
Term
what substances lower the pH of skin to 4?
Definition
sebum and fatty acids (some bacteria use sebum as a nutrient)
Term
what do keratinocytes do in regards of the immune system?
Definition
produce cytokines that stimulate cutaneous inflammation and produce chemokines that attract monocytes to site of injury
Term
what does mucus contain?
Definition
glycoproteins, proteoglycans and enzymes
Term
what does normal flora do to protect us?
Definition
prevents binding by occupying sites, utilizes nutrients that bacteria would normally use, and secretes bacteriocins that are toxic to bacteria
Term
where are lysozymes and lactoperoxidases found?
Definition
tears, mucus and saliva
Term
where are anti-microbial peptides (defensins) found and what are they most effective against?
Definition
found in mucosal secretions and cytoplasmic granules of phagocytes. effective against gram negative bacterial and enveloped viruses
Term
what does lactoferrin do? transferrin?
Definition
both bind free iron. lactoferrin in mucosal secretions and transferrin in the blood...making it unavailable to bacteria
Term
what is rubor?
Definition
redness
Term
what is dolor?
Definition
pain
Term
what is calor?
Definition
heat
Term
define tumor?
Definition
swelling
Term
what is the function of inflammation?
Definition
remove or limit spread of injurious agent, clean up the damage, repair tissue
Term
inflammation involves what?
Definition
vasodilation and vascular permeability (from cytokines, kinins and histamine), phagocyte migration (neutrophils in 30-60min, monocytes in 4-6 hours), increased phagocytosis, cytokines upregulate adhesion molecules to guide neutrophils/monocytes where to go, and plasmin to remodel/repair
Term
Mannose binding lectin binds what and activates what?
Definition
mannose on bacertia/fyeast to activate the lectin pathway of the complement system
Term
C-reactive protein binds what? and activates what?
Definition
binds LPS on bacteria/fungal walls, acts as opsonin and initiates classical complement pathway (by binding C1q)
Term
what regulates fevers?
Definition
hypothalamus
Term
what does the leader sequence do and what is it comprised of?
Definition
it traffics the protein to a cytoplasmic compartment and is comprised of mainly hydrophobic amino acids
Term
what does the leader sequence do and what is it comprised of?
Definition
it traffics the protein to a cytoplasmic compartment and is comprised of mainly hydrophobic amino acids
Term
the variable light chain is constructed from what genes?
Definition
variable gene encodes the first 95 AAs (CDR1, CDR2 and first part of CDR3)
joining gene encodes the last 13 AA (last part of DCR3)
Term
what genes encode the variable Heavy chain?
Definition
variable gene (CDR1 and CDR2)
diversity gene (first part of CDR3)
joining gene (last part of CDR3)
Term
what are recombination signal sequences
Definition
DNA sequences that regulate the recombination of genes for Variable Light and Variable Heavy chains
Term
how does κ light chain rearrangement differ from λ light chain?
Definition
Both chains have leader sequences directly preceding the gene. However in the κ chain, there are J-κ genes located just downstream of the V-κ genes, and upstream from the C-κ genes. λ light chains have the V-genes upstream followed by sequences of JC-genes (4 of them) to provide 4 different λ-light chains.
In the lambda chain, the C-lambda genes precede the 4 J-lambda genes, so there are 4 different types of lambda L chains)
Term
What is the gene rearrangement sequence in the κ light chains regarding VJC?
Definition
V-J, then VJ-C
Term
What is the gene rearrangement in the λ light chains regarding VJC?
Definition
J-C and then V-JC
Term
after rearrangement of the κ or λ light chains, what do they do?
Definition
they travel to the ER where they join the H chains to make a complete Ig molecule
Term
what do RSS's do?
Definition
located within introns, they dictate the distance and rotation of the DNA when brining antibody genes together and prevent V genes from recombining with J genes (in H Chains)
Term
What do recombinase activating genes do?
Definition
binds to RSS's and creates nicks in the DNA to remove the intervening DNA and allow the two genes to become juxtaposed
Term
Which spacer (12 or 23) is associated with the V-κ gene? The J-κ?
Definition
12 and 23 respectively
Term
which spacer (12 or 23) is associated with the V-λ gene? the J-λ gene?
Definition
23 and 12 respectively
Term
what is combinatorial diversity?
Definition
random arrangement of VDJ genes of H chains and VJ genes of L chains
Term
what is combinatorial association?
Definition
random association of H and L chains
Term
when does junctional diversity occur?
Definition
during Ig gene rearrangement
Term
Junctional diversity only affects which CDR?
Definition
CDR3
Term
What are the 3 functions of Junctional diversity?
Definition
P-nucleotide addition, Junctional flexibility, and N-Nucleotide addition
Term
N-Nucleotide addition occurs due to what enzyme?
Definition
TdT, terminal deoxynucleotidyl transferase...which can add to an exposed end 1-10 nucleotides, which then a polymerase can use to fill in the gap.
Term
Where does N-Nucleotide addition occur?
Definition
only in H chains since TdT is not present in pre-B cells during L chain rearrangement
Term
what is the only mechanism to generate diversity that occurs after gene rearrangement and after exposure to an antigen?
Definition
Somatic Hypermutation SHM
Term
what does SHM do?
Definition
introduces point mutations into the V regions
Term
What CDRs are affected by SHM?
Definition
All CDRs
Term
What is affinity maturation?
Definition
produce antibodies with a higher affinity for the antigen
Term
Where does SHM and affinity maturation take place?
Definition
in the follicle of the secondary lymphoid organ
Term
What happens during Pro-B cell stage?
Definition
RAG is upregulated to initiate VDJ rearrangement
VDJ rearrangement in variable heavy chain occurs
expression of Ig(alpha) and Ig(beta)
Term
what happens during the LARGE pre-B cell stage?
Definition
synthesis and expression of μ chain with surrogate light chains 14.1 and V preB
Igα and Igβ signal successful rearrangement of H chain genes, and H chains undergo several rounds of cell division to increase number
Term
what do Igβ and Igα do in a mature B cell?
Definition
signal to the nucleus that a antigen binded to the BCR
Term
where are Igα and Igβ located?
Definition
associated with membrane Ig molecules in ALL cells of the B lineage, until it becomes a plasma cell
Term
What happens during the small pre-B cell stage?
Definition
Upregulation of RAG genes cause L chain gene rearrangement. Expression of surrogate L chain genes (14.1 and V preB) cease. More μ chain is made but stored in ER.
Term
what is the pre-B cell receptor complex?
Definition
μ chain, 14.1, V preB, Igα, Igβ
Term
What separates immature B cells from small pre-B cells?
Definition
The L chains pair with the μ chains and form a complete BCR (IgM + Igα and Igβ).
Term
before leaving the bone marrow, what do immature B cells have to do?
Definition
interact with self antigen for self tolerance and either undergo 1. apoptosis 2. become anergic or 3. attempt receptor editing
Term
what happens to the immature B cells after leaving the bone marrow?
Definition
acquires additional surface (IgD, CR1, CR2, CD40 and L-selectin) molecules to classify it as a mature B lymphocyte
Term
A immature B cell expresses what? a mature B cell?
Definition
IgM + Igα and Igβ. IgM and IgD + Igα and Igβ
Term
What does B cell activation by TI antigens NOT result in?
Definition
memory
Term
Do antibodies undergo affinity maturation when activated by a TD antigen?
Definition
yes, they do NOT under affinity maturation when activated by a TI antigen
Term
B cell's required second signal to become activated into plasma cells comes from?
Definition
IFN-γ
Term
what are mitogens?
Definition
TI-1 antigens that tend to be components of bacterial cell walls and can activate B cells through mitogen receptors regardless of antigen specificity and do not require BCR cross linking
Term
_____ can only activate antigen specific mature B cells
Definition
TI-2 antigens
Term
Which provide a greater titer of antibodies? TI or TD antigens?
Definition
TD
Term
Describe TI-2 antigens
Definition
large structures with repeating epitopes that binding of the many epitopes by BCR cross linking generates a very strong intracellular activation signal.
Term
what happens to people who can not respond to TI-2 antigens?
Definition
highly susceptible to infection by encapsulated bacteria and suffer from immunodeficiency called Wiskott-Aldrich syndrome
Term
The bulk of pathogen specific antibody responses are produced through what kind of antigen activation? where does this occur?
Definition
TD activating B cells in secondary lymphoid tissues
Term
what region of the lymph node are DCs retained so that their processed antigens are able to be sampled by the T cells passing through?
Definition
paracortical region
Term
what is the second required signal for B cell activation?
Definition
CD40 and CD40L interaction
Term
after a B cell is activated in the lymph node, where does it migrate?
Definition
to the follicle of the lymph node so that a germinal center develops
Term
where does clonal expansion, SHM and affinity maturation, isotype switching, and differentiation into plasma/memory cells happen for B cells?
Definition
in the germinal center of the B cell while in the follicle of the lymph node????
Term
how long do plasma cells secrete antibodies?
Definition
2-4 weeks and then undergo apoptosis
Term
what does activation of a CD4+ T cell do?
Definition
release cytokines that help activate B cell and lead to further differentiation of the activated T cell to a TH1 or TH2 cell
Term
what does the CD40-CD40L interaction do?
Definition
increases expression of MHC II, CD80 and CD86 on B cells
Term
Which molecule is upregulated first when CD40 and CD40L interact?
Definition
CD86
Term
CD80 preferentially binds what? what does it do and what does this stimulate?
Definition
CTLA4, and when it does, it terminates activation of the T cell. Can bind CD28 and when it does, it provides 2nd activation signal for T cell. Stimulates a TH1 response
Term
How does hyper-IgM syndrome happen?
Definition
When people who lack functional CD40L undergo very little isotype switching, making them more susceptible to certain types of infectious agents
Term
What does CD86 preferentially bind to? what happens when it binds and what does it stimulate?
Definition
prefers CD28, and provides 2nd activation signal for T cells and stimulates a TH2 response
Term
What does CD28 do?
Definition
found on T cells and when it interacts with CD80 or CD86 on B cells, it provides the required co-stimulatory signal for full activation of the T cell
Term
What does CTLA-4 do?
Definition
found on T cells, and is upregulated upon T cell activation. It interacts with CD80 and CD86 and terminates activation of the T cell
Term
isotype switching involves specialized sequences called _____ and are found ______
Definition
switch regions. upstream (5') of each CH gene (except δ)
Term
What two steps are required for the development of T cells?
Definition
1. Selection FOR self MHC and 2. selection AGAINST those having receptors recognizing self-antigens
Term
what is MHC restriction (aka self-MHC restriction)?
Definition
the ability of T cells to recognize only our own MHC molecules
Term
what type of TCR is more numerous and more diverse than the other form?
Definition
αβ TCR
Term
which type of TCR is found in specific tissues and interacts with the non-classical MHC molecules such as CD1?
Definition
γδ TCR
Term
The V region of which TCR genes are encoded by V & J genes?
Definition
αβ
Term
the V region of which TCR genes are encoded by V, D & J genes?
Definition
γδ
Term
which TCR genes do not follow allelic exclusion?
Definition
α...so it is possible to have two different TCRs on the same T cell with two different α chains and the same β chain
Term
The TCR genes begin rearrangement with which genes?
Definition
D-J genes
Term
How does a T cell prevent it from having both types of TCR present on it?
Definition
the δ genes are located between the α genes so that when α genes rearrange, the δ genes are deleted and prevents a T cell from having both TCR types
Term
Which genes DO NOT undergo SMH, isotype switching, or combinatorial association?
Definition
TCR genes
Term
In what ways do TCR genes generate diversity?
Definition
Combinatorial Diversity (any V with any D with any J, etc.) and Junctional diversity (P-nucleotide addition, etc)
Term
Which portion of the TCR interacts with the MHC molecules and diversifies at a lower rate?
Definition
CDR1 and CDR2
Term
Where does most of the diversity take place in the TCR's CDR?
Definition
in the portion that interacts with epitopes, CDR3
Term
How does the TCR create additional diversity in the CDR3 region?
Definition
more J genes available and the 12 bp and 23 bp spacers are arranged so that the V can skip the D genes to rearrange directly with the J genes, or there can be multiple D genes involved (VJ or VDDJ, etc)
Term
T or F: TCRs follow the 23/12 rule
Definition
False, the 12/23 rule
Term
which genes do TCRs begin rearrangement with?
Definition
D-J genes, i.e. the β and δ genes
Term
What is positive selection?
Definition
Where thymocytes (double positive, CD4+ and CD8+) are subjected to thymic stromal cells expressing MHC Class I and II molecules on their surface and eliminating those thymocytes who do not interact with the MHC molecule via apoptosis. If MHC Class I interacts with CD8 co-receptor, then CD4 disappears, and vice versa.
Term
what kind of cells do CD4+ become? CD8+?
Definition
CD4+ = cytokine secreting cells
CD8+ = cytotoxic effector cells
Term
What is negative selection and where does it take place?
Definition
presentation of self-peptides complexed to either MHC Class I or II molecules, to the the single positive thymocytes by the DCs & macrophages at the cortico-medullary junction of the thymus. Those that bind strongly will die by apoptosis, and those that bind weakly will survive because they recognize the MHC but not the peptide. They will exit the thymus as a mature, single-positive T cell.
Term
What is different about γδ TCR thymocytes?
Definition
they exit thymus without being "educated", following the rearrangement of their genes. Some express CD8 co-receptors but not CD4 receptors.
Term
where are CD3 and ζ (zeta) chains found? what do they do?
Definition
they are made during the T cell development and form part of the pre-TCR and full TCR complexes. Upon successful rearrangement of the β chain genes, they are chaperoned by the CD3 and zeta chains to the surface to for the pre-TCR complex.
Term
what does the pre-TCR complex consist of?
Definition
β chain, CD3 and ζ chains
Term
what is a full TCR complex?
Definition
αβ TCR, CD3 and ζ chains) on the surface
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