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SJSU Immunology - Exam 2

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What is immunogenicity?
Ability to induce humoral and/or cell mediated response.
What is antigenicity?
Ability to bind to an antibody or a TCR.
An immunogen targets which phase of the B/T cell cycle? Which phase does an antigen target?
Immunogen targets the mature B/T cell while the antigen targets the plasma and memory Th cells.
What are some properties that contribute to immunogenicity?
1. Foreigness
2. Molecular size
3. Chemical composition and complexity
4. Antigen processing and presentation

5. Genotype
6. Experimental Immunogen
7. Adjuvants
What is the foreigness property of immunogenicity?
* Recognize non-self antigen
* Tolerance of self antigen
* The greater the difference between two species, the greater the difference between antigens
What is the molecular size property of immunogenicity?
* Most active immunogens are 100 kDa or greater
* if 5-10 kDa, then poor immunogens
What is the chemical complexity property of immunogenicity?
* Homopolymers (one type of sugar, one type of amino acid) lack immunogenicity
* Heterogeneity (different amino acids and sugars) are more immunogenic
* All four levels of protein organization are related
What is the antigen presentation and processing property of immunogenicity?
* T cells are the target of antigen presentation
- Macrophages readily phagocytose large, insoluble macromolecules
- Degraded and presented by MHC II
* Cannot degrade D-amino acids due to incompatibility with enzymes = poor immunogenicity
What are good antigens?

What do you stimulate?
Proteins and polysaccharides

The humoral immune response
What are bad antigens?

How do you transform them into good antigens?

What do they then stimulate?
Lipids and nucleic acids

Couple to carrier molecules like proteins or polysaccharides

The cell mediated immune response
What is the genotype property of immunogenicity?
* MHC gene products play a role in determining response to antigen
* Genes that encode B/T cell receptors and regulatory pathway

--> genetic variability plays an important in immunogenicity
What is the experimental immunogen property of immunogenicity?
* Low and high does induce tolerance, but repeated administration over a few weeks induces strong immune response

* Parietal administration:
- Intravenous (spleen)
- Intrdermal (lymph)
- Subcutaneous (lymph)
- Intramuscular
- Intraperitoneal
What is the adjuvants property of immunogenicity?
* Adjuvants help to boost immune response when antigen has low immunogenicity or small amount available:
- Release antigen slowly (persistance)
- Co-stimulatory signals enhanced (CD40-CD40L, B7-CD28)
- Local inflammatory response increases; attract phagocytes and lymphocytes
- Non-specific proliferation of lymphocytes
How can lipids be recognized as antigen?
Two ways:
1. Humoral response through binding to carrier molecules such as KLH and BSA
2. Cell mediated response through presentation by MHC-like molecule CD1 to TCR
Which bacterium make use of lipids on their surfaces?

What are some examples of lipids used in humans?
TB and Leprosis

Steroids and Vitamin E
What is an epitope?
Discrete sites on immunogens that bind to membrane receptors on B/T cells or antibodies.
B and T cells recognize what kind of an antigen?
B cells recognize a soluble antigen with epitopes that are highly accessible -- most often at the amino terminal end

T cells recognize the internal epitope of insoluble molecules presented by MHC -- most often at the carboxyl terminal
How does an epitope and antibody bind?
Both must have complementary shapes in order for weak, non-covalent interactions to occur
What are some characteristics of epitopes and binding sites?
* Epitope must not be bigger than the binding site
* Small epitopes fit within the deep pockets of the binding site
What are some examples of globular and small antigens?
Globular -> HEL and anti-HEL
Small -> Angiotensin II
Why are B cell epitopes located on flexible regions of the immunogen?
To maximize complementarity between the epitope and the binding site
What is an immundominant epitope?
It is one of several different epitopes found on complex proteins.

The difference is that the immunodominant epitope induces a more pronounced immune response than the others.
B cell epitopes are associated with _________________
hydrophilic amino acids on the protein surface -- usually 15 to 22 amino acids long
What are sequential and non-sequential epitopes?
sequential -> contiguous amino acids sequences of a linear antigen that fit directly into the antibody -- PROCESSING NOT NEEDED

non-sequential -> non-contiguous amino acids that are far apart in the primary structure but close together in the tertiary structure -- PROCESSING NEEDED
B and T cells are attracted to, respectively, ___________ and _____________ epitopes.
External and internal
T cells recognize this type of peptide presented by MHC II molecules.
Short linear amino acid sequences; mostly hydrophobic
What is the signifance of the open and closed loop experiment done on HEL protein in terms of epitope structure?
open loop = loss of tertiary epitope sequence and structure -- no inhibition of HEL by anit-HEL

closed loop = normal tertiary epitope sequence and structure -- inhibition by anti-HEL
What is the trimolecular complex?
MHC - Peptide - TCR
Can MHC bind to denatured protein and present it?
Yes
Does the T cell recognize soluble, native antigen?
No
What is a hapten?
Molecules that can combine specifically with the products of an immune response but CANNOT induce formation of said response.
How can a hapten induce antibody formation?
Hapten needs to conjugate with a carrier molecule to induce the formation.

The antibody will then target the hapten, the carrier, and the hapten-carrier complex.
How do you create hapten-carrier conjugates?
1. Isomerization
2. Protein binding
3. Penicillin
Are drugs hapten?

Can they induce immune response by themselves?

Do some drugs trigger allergic reactions by inducing IgE production?
No

No

Yes
What are mitogens?
Substances that are capable of non-specifically inducing DNS synthesis in T and B cells through interaction with cell surface molecules.

E.g. Lectins derived from plants
What is the difference between a mitogen and antigen?
A mitogen can stimulate more cells due to non-specificity
What is a superantigens?
They are also mitogens for T cells. These substances bind to the variable region of the beta chain of TCR and cross link to the MHC II on APCs.

Leads to antigen independent activation of T cells.
What is Pattern Recognition Receptor Proteins?
PRR recognizes the overall molecular pattern or motif.
PRR is produced by whom?
Pathogens and not the host
Where are PRR found?
PRR is found on MBL (mannose binding lectin), CRP (c reactive protein), APC, dendritic cells, and macrophages.

MBL and CRP bind to the microbial surface and promote opsonization.
What is a scavenger receptor?

What is a toll-like receptor?
Scavenger receptor is found on macrophages and dendritic cells; it aids in phagocytosis of gram+ and gram- bacteria

Toll-like receptor causes cytokine activation and release; promotes inflammatory response
What are some non-covalent forces?
H bond, ionic bond, van der waals forces, hydrophobic interactions.

They all lead to exclusion of water.
What is the affinity constant K?
It measures the strength of binding 1 epitope and 1 binding site.

High K = strong bind, readily associates

Low K = weak bind, readily disassociates
How do you determine antibody affinity?
Look to antibody and ligand experiment in aqueous container, separated by membrane.
What is avidity?
The strength of multiple interactions between a multivalent antibody and antigen (IgM).

It is often a better measure of binding capacity in biological systems.
Can an antibody with low affinity have higher avidity than an antibody with high affinity?
Yes, look at the pentameric IgM. IgM has low affinity towards antigens but high avidity as when a single antigen binds it facilitates better binding at the other sites.
What is cross reactivity?

What is an example of cross reactivity?
An antibody that is elicited by one antigen can cross react with an unrelated antigen.

An example is the ABO blood group that contains anti antibodies towards foreign blood proteins.

Another example strept. pyogenes whose M proteins can activate antibodies to cross react with myocardial and skeletal muscle proteins.
What is an example of a superantigen?
Staph bacteria causing toxic shock syndrome that cross links 1/5 of T cells resulting in high levels of cytokines
What factors make an epitope immunodominant?
1. Availability of the epitope to the receptor on T or B Cells
2. Hydrophilicity and hydrophobicity of the amino acids
3. Mobility - temperature factor
4. Linear versus assembled epitope
What occurs during the primary response of B cell interaction with antigen?
1. Initial lag
2. Increase in IgM, plateau, and decline
3. IgM predominant in circulation
4. Activation of naive lymphocytes:
- Clonal selection
- Clonal expansion
5. Production of antibody by plasma cells
6. Production of memory B cells
What occurs during the secondary response of B cell interaction with antigen?
1. Shorter lag time
2. Larger antibody population
3. Antibody lasts longer
4. IgG predominant
- Higher affinity
- Class switching, affinity maturation
5. Easier activation of memory cells
What are the three phases of B cell development?
1. Generation (naive)
2. Activation (non-naive)
3. Differentiation into plasma and memory cells
B cells can be found in which portions of the embryo?
* Fetal liver
* Fetal bone marrow
* Yolk sac
Which Ig does a mature B cell present on its cell surface when it leaves the bone marrow?
IgM and IgD
Pro B cells express what receptor on the surface?
CD45R
Differentation into pre B cell requires what?
Physical contact with bone marrow stromal cells
What are the interactions between stromal cells and pro B cells that induce pro B cells to become pre B cells?
* VCAM1 on stromal cells interact with VLA4 on pro B cells
* Stem cell factor (SCF) on stromal cells interacts with c-Kit on pro B cells
* c-Kit is activated (tyrosine kinase) allowing the cells to divide and differentiate
What interactions occur between stromal cells and pre B cells?
* Pre B cells express IL7 receptor and stromal cells release IL7
- Stimulates maturation
* Downregulation of adhesion molecules and detachment results
* Pre B cells require IL7 anyway
* IgM is the only mIg expressed on cell surface
What happens as the pre B cell leaves the bone marrow (and stromal cells)?
* Ig gene rearrangement occurs
- RAG1 and RAG2 expressed
- TdT expressed in pro B cell with N nucleotides added during heavy chain development (V to DJ rearrangement)
These co-receptors exist in pro B cells?
Ig alpha and beta heterodimer
Pre B cell receptor is associated with this heavy and light chain.
Mu heavy chain and the surrogate light chain of Vpre-B (v like) and lambda 5 (c like)
Ligands from stromal cells prevent rearrangement of the other heavy chain in pre B cells, this is action is called ___________
Allelic exclusion
The surrogate light chain in pre B cells gives way to ____________________
Gene rearrangement of the light chain
These transcription factors are important for B cell development.
1. E2A
2. EBF (Early B cell factor)
3. BSAP (B cell specific activator protein)
4. SOX-4
What happens when an immature B cell reacts with a self antigen? (See self reactive cells)

What happens when a mature B cells reacts?
Apoptosis

B cell proliferation is stimulated
Why does an immature B cell undergo apoptosis when cross-linking og mIgM occurs?

See self reactive cells
The B cell should not recognize self antigen to the degree that is does.
- Undergoes negative selection and clonal deletion
How does one go about rescuing self reactive cells?
Through light chain editing where the cell in question:
1. Arrests
2. Allows RAG1 and RAG2 to edit out incorrect light chain segments
What are the two types of antigens that the B cell will see through its development cycle?
1. Thymus independent
2. Thymus dependent
How do thymus independent antigens activate the B cell without Th cell participation?
TI-1 = polyclonal activators, such as mitogens (e.g. LPS)

TI-2 = extensive cross-link of mIg
How do thymus dependent antigens activate B cells?
Through direct contact with Th cells:
CD40 - CD40L interaction
Cross link with antigen to mIgm
What occurs after antigen challenge in terms of efferent lymphatic cellular output?
1. Usual number of cells leaving efferent lymphatics
2. Cells shutdown for 24 hours (accumulation in node, no leaving)
3. Antigen non-specific cells leave 24 to 48 hours after stimulation
4. Antigen stimulated blast cells leave to go to other nodes at 72 hours
How does antigen arrive at the lymph node?
1. Antigen arrives by afferent lymphatics, macrophages, or APCs
- Macrophages pickup antigen at sinuses
2. Interdigitating dendritic cells endocytose antigen in T cell area
3. During primary response, B cells are activated by antigen in T cell area
4. Later, follicular dendritic cells hold antigen for B cells
Do germinal centers form the first time a lymph node has been challenged with antigen?
No
When are germinal centers seen in the lymph node?
When specific B cells are recruited and activated
To initiate B cell response, an antigen must cross link two mIg receptors. True or false.
True
In order to cross link mIg receptors on B cells, an antigen must have ______________
at least 2 epitopes
What are Ig alpha and beta heterodimer?
Signal transducing heterodimer that contain an ITAM sequence on their tail end.

The ITAM sequence is activated by the cross-linking of the mIg.
The B cell co-receptor is this large complex.

What attaches to each member of the complex?
CD19, CR2, TAPA-1

CR2 + C3d + antigen
CD19 + Ig alpha and beta -> increase signal transduction
How is antigen presented in terms of MHC and Th cell?
1. Macrophage presents antigen to Th cell
2. IL1 produced by macrophage to signal Th cell (IL1-R)
3. Th cell produces IL2 to auto-stimulate itself (IL2-R)
4. Th cell migrates to edge of follicles, next to B cells
What is the interaction between Th cells and interdigitating dendritic cells?
The interdigitating dendritic cells in the paracortical areas interact with Th cells. These cells are NOT phagocytic; antigen is taken up through ENDOCYTOSIS.

These cells are efficient APC as they have long dendritic processes with which a number of Th cell can interact.
What is the interaction between Th cell and B cells?
1. The Ig receptors on B cells recognize antigenic determinants and are cross-linked
2. The Ig and antigen are endocytosed by the B cell
3. The antigen is processed and presented through MHC II
4. The B cell is a more efficient APC than macrophage -- evident during low concentration of antigen
5. Th cell and B cell interaction causes Th cell orientation of Golgi to point towards B cell
6. Cytokines from Th cell are released toward B cell
7. Proliferation and differentiation of plasma cell and memory B cells
How do B cells and Th cells physically interact?
Interaction of adhesion molecules such as CD4 binding to MHC IIand LFA1 binding to ICAM1.

CD40 molecule on B cells and the CD40L molecule on Th cells and Antigen + BCR drives B cell from G0 to G1
When is CD40L produced in Th cells
When the Th cell is activated
Which two adhesion molecules have a co-stimulator effect on B cells and Th cells?
CD40 and CD40L
B7 and CD28
What is needed to activate the B cell besides adhesion molecules, BCR and it's co-receptor, and cross-linking of the Ig?
Cytokines also act as co-stimulatory signals; e.g. IL4.
What are the four interactions a B cell needs to send it beyond G1 and into S?
1. Cross-link of Ig
2. Cytoplasmic signaling by BCR and it's co-receptor
3. Interaction of adhesion molecules (CD40 - CD40L CD4 - MHC II, LFA-1 - ICAM1)
4. Cytokines (IL4, ...)
What signals are needed for proliferation of B cells?
IL2, IL4, and IL5

IL2: acts on IL2-R; high affinity receptor composed of alpha, beta, and gamma chains

IL4: induces beta chain

IL5: induces alpha chain; constitutively present with low affinity
What signals are needed for B cell differentiation into plasma cells?
IL2: J chain production for sIgM

IL6: IgM secretion

IL2, IL4, IL5: plasma cell production of antibody
What signals cause class switching?
IFN gamma -> IgG2a
IL4 -> IgG1 -> IgE
IL5 + TGF beta -> IgA
What are the characteristics of a plasma cell?
1. Extensive RER
2. Many ribosomes
3. Extensive Golgi apparatus
4. Absence of mIg
5. End cell of B cell development
Where are primary follicles found?
Unstimulated secondary lymphoid tissues.
How early are primary follicles found?
Second trimester in the human fetus.
Lymphoid tissues which are continuously stimulated with antigens are known as _______________________
Secondary follicles with germinal centers.
What is necessary for development of secondary follicular responses?
T cells
What are the different areas within a secondary follicle?
* Dark zone
* Basal light zone
* Apical light zone
* Follicular mantle
What occurs in follicles containing germinal centers?
1.B cell + Th cell -> germinal center
2. B cells blasts move to Dark zone and become centroblast
3. Centroblasts do not have mIg
4. Centroblasts undergo somatic hypermutation to become centrocytes
- centrocytes reexpress mIg
5. With correct affinity maturation, centrocytes interact with ab-ag complexes
- can become either plasma cells (IL1, BSAP) or memory cells (move to apical light zone)
6. Plasmablasts form b/c of IL1, BSAP
7. Centrocytes internalize iccosomes producing memory cells of different Ig classes
What is needed for memory cells to be produced from centrocytes?
1. Internalization of iccosomes
2. Need Th activation
3. CD40 + CD40L
4. Need high concentrations of BSAP
5. Need low concentration of antigen
Class I and II MHC are what type of molecules?
Classical molecules
Class III MHC produces what type of proteins?
Complement proteins C2, C3, C4
Class I MHC contains which regions and what proteins do these regions produce?

Class II MHC contains which regions and what proteins do these regions produce?
Class I: A (HLA-A), B (HLA-B), C (HLA-C)

Class II: DP (HLA-DP), DQ (HLA-DQ), DR (HLA-DR)
What are the histocompatability genes in mice and humans called?
H-2 and HLA
On which cells can Class I MHC be found?

On which cells can Class II MHC be found?
Class I: All nucleated cells

Class II: On APC
Is the HLA complex polymorphic?
Yes
What does it mean if the HLA complex is polymorphic?
Each of the HLA regions in Class I and II contain several alternative genes with each gene having one allele from both the mother and father
Are HLA gene alleles co-dominantly expressed on the cell surface?
Yes
Describe the Class I MHC.
* 1 glycoprotein chain
* Part of the Ig superfamily b/c Ig domain structure present
* Two proteins chains held by non-covalent bonds
Describe the Class II MHC.
* 2 glycoprotein chains
* Part of the Ig superfamily b/c Ig domain structure
* Two protein chains help by disulfide bonds
The alpha chain of Class I MHC is encoded by ________________
MHC genes
In Class I MHC, alpha 1 and 2 are ____________ and are a good ____________ for antigen.
variable, peptide binding cleft
Alpha 3 in Class I MHC is _______________ across specifies and interacts with ____________
conserved, CD8 molecule
The alpha chain in Class I MHC has a cytoplasmic tail. True or False.
True
The variable cleft in Class I MHC is found where?
In the region between alpha 1 and 2
Describe the beta 2 chain in Class I MHC.
* Encoded by a different set of genes other than MHC genes
* Associated with MHC I through non-covalent bonds
* The absence of beta 2 causes MHC I to not be expressed
How many glycoprotein chains are in MHC II?
2
Does MHC II have both an alpha and beta chain?
Yes
What are the members of the alpha and beta chain of MHC II?

Which combinations are constant and which are variable?
alpha: alpha 1, 2
beta: beta 1, 2

constant: alpha & beta 2
variable: alpha & beta 1
May MHC II exist in dimeric form? If yes, how many TCRs and CD4s can it interact with?
Yes, 2 TCRs and 2 CD4s
Which members of the MHC II chains make up the peptide binding cleft?
alpha and beta 1
In order for a Tc response to occur, what must happen?
* Peptide of virus placed in MHC I
* MHC I interact with TCR
* CD8 on Tc cell interact with alpha 3
* CD3 must be present as well
In order for a Th response to occur, what must happen?
* Peptide associated with MHC II
* MHC II interacts with TCR
* CD4 interacts with beta 2
* CD3 must be present as well
What is physically different of peptides bound to Class I groove and those bound to Class II groove?
Class I: peptides are arch like
Class II: peptides are at constant elevation
The TCR on CD8+ Tc cell recognize what?
8-9 amino acid sequence
What type of bond occurs between peptide and the Class I groove?
Hydrogen bonding
Is the binding between Class I groove and peptide stable?
Yes
Are most MHC I molecules found unbound or bound to peptide?
Bound to peptide
What amino acids are found on the amino and carboxyl terminal of the binding cleft?
Amino: serine, valine
Carboxy: leucine, isoleucine
The TCR on CD4+ Th cell recognize how many amino acids?
13 to 18
Class I MHC picks up antigen that is ____________________ and this antigen then goes through the _______________ pathway.
Endogenous, cytosolic
Class II MHC picks up antigen that is ____________________ and this antigen then goes through the _______________ pathway.
Exogenous, endocytic
What are endogenous proteins?
viral peptides, self antigen from tumor cells
How are viral peptides in the cytosolic pathway cut?

How small are they cut?
Through the use of proteosome/proteinase found in the LMP

8 to 9 amino acids
Which subunits make up the proteosome? Where are their genes located?
LMP2, LMP7: MHC gene cluster

LMP10: non-MHC protein
What induces the LMP and its subunits to form?
IFN gamma
What is RMA-S?
It is a mutant cell line that expresses little to no MHC I on the surface.

The problem is with TAP being defective
How do you restore a defective TAP to its original function?
Transfect with gene encoding working transporter protein
Describe TAP.
* It is composed of a heterodimer (TAP1, TAP2)
* The cytoplasmic tails of the heterodimer project into the RER
* It includes an ATP binding domain
What does TAP stand for?
Transporter Associated with antigen Processing
What is the role of Calnexin?
It helps to assemble MHC I by associating with the free alpha chain. It does this by folding the alpha chain next to the TAP protein.

It dissociated when beta 2 binds
What is the role of Calreticulin and TAPAsin?
It brings MHC closer to the TAP and allows the peptide to bind with the binding site.

Both dissociate from the MHC-peptide complex and allow movement towards Golgi.
How many acidic compartments does the endocytic pathway have?

What are they?
3 compartments:

Early endosome
Late endosome
Lysosome
How many amino acids long do the acidic compartments of the endocytic pathway breakdown viral peptides?
13 to 18 amino acids
What is the function of the invariant chain in the endocytic pathway?
To prevent endogenous and unwanted peptides from binding.

To help with folding of MHC II alpha and beta chains, their exit from the RER, and routing through Golgi.
What other terms are used to name the invariant chain?
Ii, CD74
What do the three pairs of class II alpha and beta chains pair with?
A preassembled trimer of the invariant chain.
When does the invariant chain of the Class II become degraded?

What remains afterwards?
In the Golgi Complex

The CLIP (Class II associated invariant chain peptide)
Which MHC molecule exchanges the antigen peptide for CLIP?
HLA-DM (non-classical molecule)
What are the two types of TCR?
TCR1: gamma, delta
TCR2: alpha, beta
Which of the two types of TCR is more prevalent?
TCR2
Which portion of the antibody does the TCR resemble?
Fab
Is TCR a member of the Ig superfamily?
Yes
Do TCRs contain both variable and constant regions? How many CDRs does the variable region contain? Which of the CDRs is the most diverse?
Yes, 3, CDR3
What type of bond connects the two chains of the TCR (alpha and beta)?
Disulfide bonds
What is different about the gamma/delta TCR?
* Does not recognize peptide antigen; recognizes lipids and carbohydrates instead
* Does not interact with MHC; instead required CD1 gene family
A microbial phospolipid binds in which TCR and at which position?
gamma/delta TCR, deep cleft
What is the difference in angles between alpha/beta and gamma/delta TCR?
149 degree for a/b
111 degree for g/d
Which of the chains on the TCR are light chain and which are heavy chain?
light chain: alpha, gamma
heavy chain: beta, delta
Are the alpha and delta chain genes on the same chromosome?

Are the delta chain genes within the alpha chain genes?
Yes

Yes
Which is more diverse the beta or the delta chains and why?
Beta chain is more diverse because it contains more J gene segments while the delta chain contains less J and C gene segments.
What are the five types of diversity seen in TCRs?
1. Combining gene segments
2. Combining chain segments
3. Combining different delta segments
4. Use of alternative triplets
5. Use of nucleotide additions (N and P)
With what accessory molecules is the T cell associated with and what are their functions?
CD3: Couples to TCR and acts as signal transduction.

CD4/CD8: Binds to the MHC protein; co-receptor for activation.

CD18 (LFA1): Adhesion molecule

CD45: Possible down-regulation by removing phosphate groups.
How many domains does CD4 have? What are they?
4; D1 to D4
CD8 is made up of what domains?
alpha/beta heterodimer
When a lymphoid progenitor cell leaves the bone marrow, which molecules are expressed and which are not expressed?
Expressed: CD44, CD25, and c-Kit

Not expressed: CD4, CD8, CD3, alpha/beta or gamma/delta heterodimer
What is the function of the CD44 molecule, the c-Kit receptor, and CD25 molecule?
CD44: adhesion molecule used in homing to the thymus

CD25: alpha chain of the IL2 receptor

c-Kit: receptor for stem cell growth factor
When is the first time that the CD3 molecule is expressed?
During the pre T cell phase when the beta chain is created on the cell surface.
What is the function of the CD3 molecule?
It is used as a signal transduction protein much like Ig alpha/beta in B cells.
When the alpha/beta chains rearrange, which two genes are turned on immediately before hand?
RAG1 and RAG2
Which rearranges first the gamma/delta or alpha/beta chains in TCR?
gamma/delta
At what phase in the T cell development cycle, can a T cell recognize ligand in the thymus? How does it send a signal?
pre T cell, CD3 molecule
Propose two models that explain the transformation of double positive cells to single positive lineage.
Instructive model: an engagement signal for either CD4+ or CD8+ is sent resulting in the downregulation of the other.

Stochastic model: downregulation of CD4+ or CD8+ is a random process that cannot be readily explained.
Upon interaction with antigen, T cell genes can be grouped in three categories. What are they?
Immediate genes: transcription factors

Early genes: IL2, IL2R, IL3, IL6, IFN gamma

Late genes: various adhesion molecules
What two signals are needed to activate a T cell?
1. Ag + TCR-CD3
2. B7 + CD28 (costimulatory signal)
Which inhibitory signal regulates the function of the B7-CD28 costimulatory signal?
CTLA4 + B7
B7 + CD28 costimulatory signal on T cell activation leads to what?
IL2 and IL2 receptor expression; IL2 self-stimulates the T cell leading to proliferation of either Effector or Memory cells
What is a superantigen and what does it do?
Superantigens have the unique capacity to crosslink MHC class II molecules on antigen presenting cells simultaneously with T-cell receptors on helper TH cells, bringing these cells together and falsely inducing their activation.
Gamma/delta T cells are made up of which gamma and delta subtypes?
gamma 9 and delta 2

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