Term
| What is the first antibody released by B-cells at the initial insult of a new infection? |
|
Definition
|
|
Term
| What antibody is released at the second exposure? |
|
Definition
|
|
Term
| If you do a test and find that IgM is present, what does it mean? |
|
Definition
| PRIMARY INFECTION- SOMETHING NEW |
|
|
Term
| What are some capabilities of IgG? |
|
Definition
Opsonization, crossing the placenta-
IgG is the immunity that mom gives the baby |
|
|
Term
| What regions of IgM and IgD are identical, and what regions are different? |
|
Definition
| IgM and IgD both have the same antigen binding specificity, but the membrane region (CONSTANT REGION) is different on each |
|
|
Term
| What does it mean if you do a test and find both IgM and IgD? |
|
Definition
| You are looking at Naive B-cells |
|
|
Term
| Which antibodies can activate complement? |
|
Definition
| Both IgG and IgM can activate complement |
|
|
Term
| What happens with IgG opsonization? |
|
Definition
| IgG binds to a pathogen and BRINGS IT TO A PHAGOCYTE |
|
|
Term
|
Definition
| Antibody-dependent cellular cytotoxicity- similar to opsonization but we are BRINGING A VIRALLY INFECTED CELL TO AN NK CELL TO DIE |
|
|
Term
| What region of the antibody gives biological activity? |
|
Definition
|
|
Term
| What region of the antibody plays a role in opsonization? |
|
Definition
The Fc region of the antibody bind with the FcReceptor- THIS IS THE CONSTANT REGION
-don't forget that C3b complement protein is a major opsonin |
|
|
Term
| What is the story with ADCC? |
|
Definition
| A virus infects a cell, the cell expresses non-self proteins on its surface, these non-self proteins are recognized by antibodies, and the viral infected cell is brought to NK cells for destruction |
|
|
Term
| What is the difference between the T-cell receptor and B-cell antibodies? |
|
Definition
T-cell receptors are not reproduced, and are NOT bivalent-
T-cell receptors cannot recognize free antigen- they must have antigen presented to them on MHC |
|
|
Term
| What is the function of Helper T-cells? |
|
Definition
-express CD4 and bind to antigen + Class II MHC
-release cytokines that direct macrophages to kill bacteria
-make IL-4 and IL-5 which help B-cells produce antibodies- specifically, these cytokines help with class switching from IgM to Ig-whatever-is-needed |
|
|
Term
| Where does Interferon γ come from and what does it do? |
|
Definition
Interferon γ is made by Helper T-cells and it DIRECTS MACROPHAGES TO KILL BACTERIA
***Interferon γ turns macrophages into the incredible hulk*** |
|
|
Term
| What is the function of Cytotoxic T-cells? |
|
Definition
These are direct killing machines:
-they express CD8 and bind to antigen+Class I MHC
-they are cytotoxic- they directly lyse and kill infected cells |
|
|
Term
| How do Cytotoxic T-cells prompt apoptosis? |
|
Definition
The TC binds to Fas expressed on the viral infected cell, and a signal is sent to the viral infected cell to kill itself
-A CALCIUM DEPENDENT ENDONUCLEASE CHOPS UP CELLULAR DNA AND THE CELL DIES |
|
|
Term
| In what fraction of the serum do we find antibodies? |
|
Definition
|
|
Term
| What are the functions of antibodies? |
|
Definition
-Opsonization
-Neutralization of viral infections
-ADCC |
|
|
Term
| What types of chains make up an antibody? |
|
Definition
| 2 identical heavy chains and 2 identical light chains |
|
|
Term
| How many domains do light chains have? |
|
Definition
2 Domains- 1 variable and 1 constant
VC |
|
|
Term
| How many domains do heavy chains have? |
|
Definition
| 4-5 domains: 1 variable and 3-4 constant |
|
|
Term
| What types of bonds hold antibodies together? |
|
Definition
|
|
Term
Which region of the antibody binds to antigen?
Which region is bound to cellular receptors and is bioactive? |
|
Definition
Fab binds to antigen and is variable
Fc binds to cellular receptors |
|
|
Term
| How many classes of heavy chain are there, and what do we call them? |
|
Definition
There are 5 classes of heavy chain-
These make different ISOTYPES
They are: μ,δ,γ,α,ε- we call them M,G, D, A, and E |
|
|
Term
| What segments make up the heavy chain? |
|
Definition
Variable (V), Diverse (D), Joining (J)
These are randomly selected by the developing B-cell |
|
|
Term
| What segments make up the light chain? |
|
Definition
| Variable (V) and Joining (J) |
|
|
Term
| What segments (VJD) have the most variability? |
|
Definition
| There are 100's of V segments, but only several D and J segments |
|
|
Term
| What are the 2 classes of light chain? |
|
Definition
| (κ and λ)- these DO NOT DETERMINE ISOTYPE |
|
|
Term
| What is the gene locus for the heavy chain? |
|
Definition
|
|
Term
| What is the λ gene locus for the light chain? |
|
Definition
|
|
Term
| What is the κ gene locus for light chains? |
|
Definition
|
|
Term
| What segment does the heavy chain have that the light chain is missing? |
|
Definition
The D segment-Diverse segment
LIGHT CHAINS HAVE NO D |
|
|
Term
| At what level do the antibody recombinatorial events occur? |
|
Definition
|
|
Term
| Which chain segment rearrangement occurs during B-cell development in the bone marrow? |
|
Definition
| V (variable) rearrangements take place in an ORDERED sequence during B-cell development in the Bone Marrow |
|
|
Term
| Which chains rearrange first? |
|
Definition
| Heavy chains rearrange first, followed by light chains |
|
|
Term
| What enzymes facilitate rearrangements in B and T cells? |
|
Definition
| RECOMBINASES- RAG1 and RAG2 |
|
|
Term
| What are the clinical consequences of a defect in antibody gene rearrangement? |
|
Definition
| SCID- severe combined immunodeficiency |
|
|
Term
|
Definition
-deletion of RAG1 and RAG2
-rearrangement only effects variable region
-SCID looks like Graft-vs Host Disease (GVHD) |
|
|
Term
| What are 5 mechanisms to generate receptor diversity? |
|
Definition
-existence in genome of multiple VDJ segments (B and T cells)
-VDJ recombination with RAG1 and RAG2
-N-nucleotide addition
-combinatorial association of heavy and light chains
-Somatic Hypermutation- increases specificity |
|
|
Term
| What is N-nucleotide addition? |
|
Definition
-the end result of RAG action is a hairpin in the AA chain
-this is cleaved and TdT adds nucleotides at random between D and J junction
-these nucleotides are non-templated |
|
|
Term
| What does the presence of TdT signify? |
|
Definition
| This is an early marker of B and T cell development |
|
|
Term
| What is allelic exclusion? |
|
Definition
-How we get antigenic specificity
-even though B-cells are diploid, they only express the rearranged heavy chain genes from 1 chromosome and the light chain genes from 1 chromosome
-if heavy chain from mom's DNA is productive, the heavy chain from dad's doesn't do anything |
|
|
Term
| What are some important things about IgG? |
|
Definition
-it's the best of all antibodies
-Opsonization
-ADCC
-activation of CLASSICAL complement pathway
-can cross placenta
-has 4 isotypes |
|
|
Term
| What is the predominant antibody in serum? |
|
Definition
|
|
Term
| What are some important things about IgM? |
|
Definition
-ALWAYS THE FIRST ANTIBODY
-first antibody in neonates
-can activate CLASSICAL complement pathway
-pentameric in serum- J chain in the middle
-High avidity, low affinity |
|
|
Term
| How many binding sites are there on IgM? |
|
Definition
| 10 (remember, it is pentameric) |
|
|
Term
| What are some important things about IgA? |
|
Definition
-PREDOMINANT ANTIBODY IN SECRETIONS
-mucosal surfaces, saliva, tears, nasal fluids, sweat, colostrum, breast milk
-DIMER- J chain in the middle
-breast feeding transfers IgA |
|
|
Term
| What protects IgA in secretions? |
|
Definition
A piece that blocks enzymes from degrading it by creating STERIC HINDERANCE across the dimeric antibody
-this piece is secreted by epithelial cells |
|
|
Term
| What are some important things about IgE? |
|
Definition
-Important for TYPE I HYPERSENSITIVITY
-binds to Mast Cells and Basophils
-specific for parasites |
|
|
Term
| What are some important things about IgD? |
|
Definition
| -only real function is it's role as part of the B-cell receptor |
|
|
Term
| What are the only 2 antibodies that trigger complement activation? |
|
Definition
|
|
Term
| If a patient presents with recurrent mucosal infections, we should suspect a problem with what? |
|
Definition
|
|
Term
| What are the 2 stages of B-cell development and where do they occur? |
|
Definition
-Antigen Independent- development of B-cells from PHSC's in the bone marrow
-Antigen Dependent- the education of B-cells in the primary and secondary lymphoid tissue- results in mature B-cell that become either plasma cells or memory cells |
|
|
Term
| What are the intermediates of B-cell development? |
|
Definition
| PHSC->Lymphoid Progenitors->Progenitor B-cells (PRO-B)->Precursor B-cells (PRE-B)->Immature B-cells->Mature B-cells to memory or plasma cells |
|
|
Term
| What cells in the bone marrow secrete important cytokines for B-cell development? |
|
Definition
|
|
Term
| At which stage in B-cell development do we start to see IL-7 and what does it do? |
|
Definition
| Pre-B stage; IL-7 is important in B and T-cell development and helps with Differentiation |
|
|
Term
| At which stage do we see RAG1/2? |
|
Definition
| rearrangement through PRE-B |
|
|
Term
|
Definition
|
|
Term
| When does the light chain rearrangement occur? |
|
Definition
|
|
Term
| When do we first see expression of IgM? |
|
Definition
|
|
Term
| When do we first see expression of IgD? |
|
Definition
|
|
Term
| What are some important events during the Pro-B stage? |
|
Definition
-heavy chain rearrangements
-CD19 and CD20 show up, but still no receptors |
|
|
Term
| What are some important events in the Pre-B stage? |
|
Definition
-cytoplasmic mu- IgM heavy chian before light chain rearrangment- BEFORE Ab SURFACES
-CYTOPLASMIC MU IDENTIFIES THE PRE-B STAGE |
|
|
Term
| What are some important events during the immature B-cell stage? |
|
Definition
-first time cells can read antigen
-selection for B-cells
-IgM+, IgD- |
|
|
Term
| How can we use our knowledge of B-cell development to stage lymphoma? |
|
Definition
Look at biomarkers to see at which stage the cancer is happening-
i.e. if CD19+, IgM+, IgD-, we would be looking at Immature B-cells |
|
|
Term
| What are the parts of the B-cell receptor and what does it do? |
|
Definition
| IgAlpha and IgBeta- these are accessory molecules embedded in the membrane on either side of the antibody that are responsible for SIGNAL TRANSDUCTION |
|
|
Term
| What is necessary for Heavy Chains to surface? |
|
Definition
|
|
Term
| What are the components of the special surrogate light chain that occurs before the light chain surfaces? |
|
Definition
|
|
Term
| What happens if a B-cell recognizes "self antigen"? |
|
Definition
| Clonal Deletion and Apoptosis |
|
|
Term
| What do T-cell dependent antigens require? |
|
Definition
| Direct contact of a B-cell with a Helper T-cell for B-cell activation |
|
|
Term
| What proteins trigger B-cell activation in the case of T-cell dependent antigens? |
|
Definition
CD40 binds to CD40Ligand on the TH cell
-THIS HELPS B-CELLS MAKE BETTER ANTIBODIES |
|
|
Term
| What are T-cell INDEPENDENT antigens? |
|
Definition
Mitogens that induce B-cell activation:
-No help from T-cells
-Weaker
-IgM is the only antibody formed
-no memory response
-no class switching |
|
|
Term
| What can be generated only with T-cell dependent response? |
|
Definition
IgG, from class switching
-not a polyclonal activator |
|
|
Term
| What protein interaction on B-cells and TH cells is critical for class switching? |
|
Definition
|
|
Term
| What happens in the Germinal Center of secondary lymphoid tissue? |
|
Definition
-class switching
-affinity maturation
-differentiation into Memory B-cells or Plasma Cells |
|
|
Term
| Which Ab has higher affinity? |
|
Definition
|
|
Term
| What happens to antibody affinity as the immune response progresses? |
|
Definition
| Affinity INCREASES during an immune response |
|
|
Term
| What is affinity maturation? |
|
Definition
DNA polymerase gets overworked and misses some tiny point mutations which occur in the rearranged VDJ's
-the net effect is increased affinity |
|
|
Term
| What is Hyper IgM Syndrome? |
|
Definition
T-cells do not express CD40L, so the bond to CD40 cannot happen, so there is NO CLASS SWITCHING
-the only Ab that can be made is IgM |
|
|
Term
| What type of class switching is caused by IL-4? |
|
Definition
|
|
Term
| What type of class switching is caused by IL-5? |
|
Definition
|
|
Term
| If B-cells cannot be activated, what proteins are probably at fault and what do they do? |
|
Definition
| IgAlpha and IgBeta- they initiate a signal cascade that includes ITAM18, Syk, etc |
|
|
Term
| Which B-cell CD marker is critical for Epstein Barr? |
|
Definition
|
|
Term
| What makes up the B-cell co receptor and what happens if it is missing? |
|
Definition
| CD19, CR2, TAPA-1- if missing, more antigen is needed to activate B-cells |
|
|
Term
| What is the principal function of the B-cell co-receptor? |
|
Definition
| Lower the threshold of antigen needed to activate the B-cell |
|
|
Term
| What CD marker on the T-cell connects to B7 on the B-cell? |
|
Definition
|
|
Term
| What type of enzymes have an important role in B-cell cycle regulation? |
|
Definition
|
|
Term
| What happens when B-cells are turned on but cannot be turned off? What is this called? |
|
Definition
| Cancer; Constitutive Activation |
|
|
Term
| What are the 3 major steps for T-cell dependent antigens to activate B-cells? |
|
Definition
-Bonding of the B/T conjugate
-CD40 binds with CD40L *ABSOLUTE REQUIREMENT
-B-cell progression signal is induced by cytokines from the Helper T-cell |
|
|
Term
| What cytokines activate B-cell class switching, maturation, and differentiation? |
|
Definition
From Helper T-cells:
IL-2, IL-4 and IL-5 |
|
|
Term
| What is considered the HALLMARK of humoral immunity? |
|
Definition
|
|
Term
| What region of the antibody is rearranged during class switching? |
|
Definition
|
|
Term
| What are some symptoms of Hyper IgM Syndrome and what is it's cause (again)? |
|
Definition
Recurring infections
Chronic diarrhea because there is no IgA
Caused by mutation in CD40L on TH cells |
|
|
Term
| What activates B-cells to mature into plasma cells? |
|
Definition
| Follicular Dendritic Cells deliver IL-1, CD23 |
|
|
Term
| What activates B-cells to mature into memory cells? |
|
Definition
The activated B-cell binds to Ag complexes on the Follicular Dendritic Cell membrane
-CD40/CD40L interaction |
|
|
Term
| What is the gene locus for HLA (MHC)? |
|
Definition
|
|
Term
| What are the features of Class I MHC? |
|
Definition
Has A, B and C types
Works with Cytotoxic T-cells
Highly Polymorphic |
|
|
Term
| What are the features of Class II MHC? |
|
Definition
Has DP, DQ, and DR types
Works with Helper T-cells |
|
|
Term
| What is unique about the alleles for HLA (MHC)? |
|
Definition
| -CODOMINANCE- both alleles are contributing |
|
|
Term
| What type of antigen does Class I HLA present? |
|
Definition
|
|
Term
| What type of antigen does Class II MHC present? |
|
Definition
|
|
Term
| Where is Class I HLA expressed? |
|
Definition
|
|
Term
| What are the parts of the Class I HLA protein? |
|
Definition
Alpha chain and Beta2 microglobulin
-alpha 1 and alpha 2 domains make a cleft and bind to short peptides |
|
|
Term
| What happens if Beta2 Microglobulin is mutated or deleted? |
|
Definition
NO CLASS I BONDING because Beta2 microglobulin is required for proper folding of the molecule
-This means there will be no Cytotoxic T-cell activity |
|
|
Term
| Where is Class II HLA expressed? |
|
Definition
| ANTIGEN PRESENTING CELLS- macrophages, B-cells, dendritic cells |
|
|
Term
| What makes up the Class II MHC protein? |
|
Definition
Alpha and Beta Chain
Can handle larger peptides |
|
|
Term
| Key elements of ENDOGENOUS antigen processing and presentation |
|
Definition
-viral proteins cut by PROTEOSOMES
-HLA is in the ER and peptides in cytoplasm
-TAP1 and TAP2 load HLA by making tunnels that use ATP to pierce the ER
-the HLA Class 1+ Antigen travels to surface by vesicular transport
-SMALL PEPTIDES
-very unstable |
|
|
Term
| Key elements of EXOGENOUS antigen processing and presentation |
|
Definition
-Class II is only on antigen presenting cells, which also have Class I
-Class II is locked by INVARIANT CHAIN until the exogenous antigen is phagocytosed into the cell and the Class II is exocytosed by the ER
-when they meet, the environment breaks off the INVARIANT CHAIN and they can bond-
-this bubble is called a phagolysosome |
|
|
Term
| What happens if cells are missing Class I MHC? |
|
Definition
| They will be attacked by NK cells that do not recognize them as self |
|
|
Term
| What cytokines increase expression of Class II MHC, and how? |
|
Definition
| IFNγ, TNF- induce transcription factors that bind to promotors of MHC genes |
|
|
Term
| What happens when CMV binds to Beta2 Microglobulin? |
|
Definition
| Prevents assembly of MHC Class I |
|
|
Term
| What is the most important inflammatory cytokine? |
|
Definition
|
|
Term
| What is the function of IL-8? |
|
Definition
| Chemoattractant for NEUTROPHILS |
|
|
Term
|
Definition
| Cell uses cytokine to interact with another cell, OR ITSELF |
|
|
Term
|
Definition
| Cell interacts with cytokine |
|
|
Term
|
Definition
Cell secretes cytokine into circulation to effect a distant cell
-Good example is EPO- made in the kidney but works in the bone marrow |
|
|
Term
|
Definition
Cytokine does multiple things:
IL-4 works on B-cells, thymocytes, and Mast cells |
|
|
Term
|
Definition
Multiple cytokines do the same thing:
IL-2,4,5 all cause B-cells to proliferate |
|
|
Term
|
Definition
Multiple cytokines act in conjunction:
e.g. IL-4,5 induce B-cells to class switch to IgE |
|
|
Term
|
Definition
Cytokines can shut stuff off:
-like blocking class switching, shutting down TNF-α, etc. |
|
|
Term
| What is the function of IL-2? |
|
Definition
ACTIVATES T and B-CELLS and NK CELLS and helps them proliferate
-it is made by T-cells and is autocrine regulated |
|
|
Term
| What are the functions of IL-4 and 5? |
|
Definition
To help B-cells differentiate Ig via class switching
-IL-4-> IgM to IgG and IgE
-IL-5-> IgM to IgA |
|
|
Term
| Mutations in the chain of the IL-2 receptor lead to: |
|
Definition
| SCID- Bubble Boy Syndrome |
|
|
Term
| INF Alpha is used to treat: |
|
Definition
|
|
Term
| INF Beta is used to treat: |
|
Definition
|
|
Term
|
Definition
ACTIVATES MACROPHAGES
-stimulates intracellular killing
-inhibits TH2 response
-can be used to treat chronic infections and TB |
|
|
Term
| What 3 cytokines promote inflammation and fever? |
|
Definition
| Pyrogenic Cytokines- IL-1, IL-6,TNF-α |
|
|
Term
| What effect does TNF-α have on dendritic cells? |
|
Definition
| It stimulates migration of dendritic cells to lymph nodes and promotes their maturation- INITIATES ADAPTIVE RESPONSE |
|
|
Term
|
Definition
| Macrophages, T-cells, Fibroblasts |
|
|
Term
| What are the uses of TNF-α inhibitors? |
|
Definition
Use monoclonal antibodies to inhibit TNF alpha in cases of arthritis or autoimmunity-
-supressing TNF alpha can down-regulate inflammation but leaves the patient immunocompromised |
|
|
Term
| What are Monoclonal antibodies? |
|
Definition
| Antibodies that are specific to ONE EPITOPE on a single antigen |
|
|
Term
| What are Polyclonal Antibodies? |
|
Definition
| Antibodies that can bind to MULTIPLE EPITOPES on a single antigen |
|
|
Term
|
Definition
It acts on PLASMA CELLS to drive antibody production
-it can help class-switch to IgG |
|
|
Term
| What is the clinical use of IL-6 inhibitors? |
|
Definition
| To treat Rheumatoid Arthritis |
|
|
Term
| What is the clinical use of IL-2 inhibitors? |
|
Definition
| Blocking IL-2 signalling is useful for immunosuppression after transplantation |
|
|
Term
| What is the clinical use of IL-4 inhibitors? |
|
Definition
| Monoclonal Ab against IL-4 can treat serious allergies (REMEMBER ALLERGIES ARE CONNECTED TO IgE) |
|
|
Term
| What is the function of IL-10? |
|
Definition
It is the most potent cytokine
IT SHUTS DOWN THE IMMUNE RESPONSE
-made by macrophages
-down-regulates pro-inflammatory cytokines |
|
|
Term
| What is the function of IL-12? |
|
Definition
This is the first cytokine made after interaction with pathogen
-made by macrophages
-induces TH cell differentiation into TH1 cells
-SYNERGIZES with IL-18 to induce IFN gamma from TH1 cells |
|
|
Term
| What do chemokines do? Give an example |
|
Definition
Chemokines attract leukocytes to inflammation-
-a good example is IL-8, which attracts neutrophils |
|
|
Term
| What is the function of IL-3? |
|
Definition
This is a major growth factor for WBCs
-STIMULATES PHSC to generate MYELOID PROGENITORS- these end up making erythrocytes, megakaryocytes, granulocytes, dendritic cells, and monocytes
-secreted by basophils and T-cells |
|
|
Term
| What is the function of IL-7? |
|
Definition
Growth factor for T and B cells
-helps with lymphocyte differentiation |
|
|
Term
| What do high levels of IL-7 signify? |
|
Definition
|
|
Term
| What is the function of GM-CSF? |
|
Definition
Granulocyte/monocyte growth factor
-Boosts immunity during chemotherapy |
|
|
Term
| What is the function of M-CSF? |
|
Definition
|
|
Term
| What is the function of G-CSF? |
|
Definition
NEUTROPHIL PRODUCTION from granulocytes
-use this to boost neutrophils before a bone marrow transplant |
|
|
Term
| What is the function of erythropoietin (epo)? |
|
Definition
| Growth factor for Red Blood Cells |
|
|
