Immunology (Bbd Exam I)

Front 1

CD4

Back 1

1. Receptor protein that says its a T Helper Cell

Front 2

CD3, CD28

Back 2

1. Bind with B7.1 and B7.2

Front 3

LFA-1

Back 3

1. Binds with ICAM-1

Front 4

Proteins involved in binding T Cell recognition

Back 4

CD3, CD4, CD28, B7.1, B7.2, ICAM-1, LFA-1

Front 5

Name the states of B-cell activation

Back 5

1. Contact and recognition of microorganism
2. Activation signals through BCR and via T-helper Cells
3. Clonal expansion and differentiation
4. Antibody secretion
5. Isotype switching
6. Affinity maturation

Front 6

What are the three B-cell subsets and what are their locations?

Back 6

1. B-1 Cells: primitive B-cells, make IgM, recognize polysaccharides and lipids, located in mucosa and peritineum
2. B-2 Cells: conventional B-cells, make different isotypes, located in secondary lymph tissue, recognize proteins
3. Marginal Zone B-cells: primitive function, located in spleen white pulp

Front 7

Which immunoglobulins are primarily secreted during primary/secondary response?

Back 7

1. Primary - IgM (lower levels)
2. Secondary - IgG (higher levels)

Front 8

What are the 4 major transcription factors in B-cell signaling?

Back 8

1. NFkB
2. ***NFAT***
3. AP1
4. Myc

**these factors play a role in cytokine production**

Front 9

Describe the NFAT pathway

Back 9

1. Cross-linking of antigen/Ig
2. Tyrosine phosphorylation events
3. Biochemical intermediates (PLC, Ras, GTP/GDP)
3. Enzyme activation (Ca dependent Kinase, PKC, ERK)
4. Activation of transcription factors (NFkB, NFAT, AP-1, Myc)
5. Production of necessary cytokines

Front 10

What role does compliment play in B-cell responses?

Back 10

1. Compliment receptors (CR2 and C3d) help in the signal cascade with B-cell activation

(C3d binds microbe, CR2 is a membrane-bound receptor on B-cells)

Front 11

What three events happen when the T-helper cell and the Activated B-2 cell meed in the lymph node?

Back 11

1. Isotype switching
2. Affinity maturation (with the help of an APC - dendridic cell)
3. Amplification (via cytokines secreted from T-helper cell)

Front 12

Which receptors aid in "communication" of B-cells and T-helper cells?

Back 12

1. CD40 receptor on the B-cell
2. CD40L receptor on the T-helper cell

**this aids in B-cell proliferation/maturation

Front 13

Name the Major Ig classes and their general functions

Back 13

1. IgM - compliment fixation
2. IgG - Opsonization, viral neutralization
3. IgE - Mast cell degranulation, helminthes
4. IgA - Mucosal immunity (transport through epithelial cells)

Front 14

Name the cytokines involved in isotype switching that are secreted from a T-helper cell to induce changes in secreted immunoglobulins from a mature B-cell

Back 14

1. No cytokines - IgM secreted
2. IFN gamma - IgG and subclasses secreted
3. IL-4 - IgE secreted
4. TGF beta - IgA

Front 15

During isotype switching, which regions of the BCR are modified?

Back 15

1. NOT the variable regions... those remain constant to recognize the programmed antigen
2. they DO modify the CONSTANT region of the HEAVY CHAIN in Ig isotype switching

Front 16

During affinity maturation, what region of the antibody (BCR) undergoes mutation when it comes in contact with the antigen over and over again?

Back 16

CDR1, CDR2, and CDR3

**hypermutations in the CDRs increase affinity to the antigen with repeated exposures**

Front 17

During inhibition of B-cell response, which receptor binds the antigen-bound antibody back to the T-cell?

Back 17

1. the Fc receptor... which leads to inhibition of B-cell response

Front 18

Discuss active vs. passive immunity

Back 18

1. Passive immunity - transfer of pre-formed antibodies from an already immune individual
2. Active immunity - could be from natural infection (chicken pox), or vaccination; your body undergoes an immune response and develops memory B-cells

Front 19

How do antigens end up in the secondary lymph organs?

Back 19

1. They migrate there to be discovered by B and T-cells. They can either migrate there as free microbes or be carried by dendritic cells that have already picked up the antigen
2. **remember** they have to squeeze through the HEV in the lymph node to enter the lymph tissue

Front 20

What is the main function of the spleen in the immune response?

Back 20

1. Blood borne antigens are trapped here and concentrated in dendritic cells and macrophages in the spleen

Front 21

In general, name the membrane bound receptors involved in signal transduction in B-cells.

Back 21

1. B-cell receptor complex - Proteins IgAlpha, IgBeta... I think compliment is involved too (C3d on microbe, and CR2 which is membrane bound to the B-cell

Front 22

In general, name the membrane bound receptors involved in signal transduction in T-cells.

Back 22

1. The TCR complex involves Proteins CD3 and Zeta (which are not in direct contact with the MHC/Antigen/TCR - but are associated with it (the signal cascade actually starts from the CD3/Zeta proteins in activation of the T-cell

Front 23

In the signal transduction cascade, what role does CALCINEURIN play?

Back 23

1. Calcineurin dephosphorylates (which ACTIVATES) proteins, and begins cascade of the NFAT pathway (Nuclear Factor of Actaviting T-cells)

Front 24

Antibody Structure...

Back 24

1. composed of a heavy and light chain (2 heavy/2 light)
2. Heavy chain has 1 variable and 3 constant regions
3. Light chain has 1 variable and 1 constant region

**also remember that each variable region has 3 HYPERvariable regions**

Front 25

HYPERVARIABLE regions are what determine the complimentarity of the antibody, what are these regions referred to as?

Back 25

1. CDR1, CDR2, and CDR3 (CDR3 has the greatest variability and is located at the junction of the V/C regions)

**this hypervariability allows for the identification of the millions of antibodies out there**

Front 26

What varieties do the light chains possess?

How is that clinically relevant?

Back 26

1. Kappa and Lambda varieties
2. LCDD (Light Chain Deposition Disease) where light chains are deposited into multiple organs - 80% are due to Kappa chains

Front 27

Define "cross reactivity"

Back 27

1. when an antigen that elicits an immune response looks "close enough" to that of another antigen, so the immune system acts on that tissue/microbe as well (can be good as in HSV or bad as in autoimmune disease)

Front 28

Describe the TCR structure

Back 28

1. Looks very similar to the Fab (Fc) region of an antibody
2. same numbers of V and C regions (3/1) with 3 CDR regions within the variable regions
2. Composed of Alpha/Beta chains rather than Heavy/light chains (can also be gamma/delta chains)

**TCRs do NOT undergo affinity maturation**

Front 29

Which cytokine is associated with SCID and why?

Back 29

1. IL-7 - it is involved in the proliferation of B, T, and NK cells in the Bone marrow and Thymus
2. NOT TO BE CONFUSED with IL-2 which is involved in clonal expansion of B and T-cells (secreted by CD4 T-cells as cytokines)

Front 30

What to V, D, J, and C stand for?

Back 30

1. V - Variable region genes; many
2. Diversity gene segment
3. Joining gene segment
4. Constant region; one or a few

Front 31

Cytokines
Stimulates Eosinophils

Back 31

IL-3
IL-5
GM-CSF

Front 32

Cytokines
Stimulates Mast Cells

Back 32

IL-3 (SCF)
IL-9

Front 33

Cytokines
Stimulates IgE production

Back 33

IL-4
IL-9
IL-13

Front 34

Cytokines
Suppresses T-Helper 2 reactions

Back 34

IL-2
IL-10
IL-12
IF-gamma

Front 35

In regards to T-cell and B-cell selection, what is AIRE?

Back 35

1. AIRE is Autoimmune Regulator Enzyme - it causes apoptosis of the T-cells that bind to self antigens in primary lymph organs with HIGH AFFINITY

**has clinical relevance**

Front 36

What is APS-1 (a syndrome)?

Back 36

1. APS-1 is Autoimmune Polyendocrine Syndrome 1 - its caused by a mutation in AIRE (if AIRE is defective, negative selection in the primary lymph organs will be disabled and T and B cells with high affinity to self will be "let through" to peripheral tissues, thus causing autoimmune disorders of multiple organs

**inhibits "central tolerance"**

Front 37

Associated disorders of APS-1 are...

Back 37

1. Hypoparathyroidism
2. ADDISONS DISEASE (Adrenal failure)
3. Ovarian failure

Front 38

What are the main mechanisms of peripheral T-cell tolerance?

Back 38

1. Activation-induced cell death (AICD)
2. T-cell anergy (just lowering "sensitivity" of T-cell to it's epitope)
3. Suppression by cytokines released by T-reg cells

Front 39

Normally, when we recognize a "self-antigen" we utilize the active-induced cell death (AICD) mechanism... describe this mechanism -

Back 39

1. Normally, IL-2 would be secreted if a naive T-cell recognized a foreign antigen. If a naive T-cell recognizes a self-antigen, then IL-2 is inhibited

Front 40

What is Autoimmune Lympho-Proliferative Syndrome (ALPS)?

Back 40

1. ALPS happens when there is a deficiency in the activation-induced Cell Death pathway (Specifically, a defect in the Fas/FasL mechanism)
2. leads to accumulation of T/B-cells in lymph tissues

Front 41

What is the Fas/FasL mechanism?

Back 41

1. It is another mechanism related to the Activation-Induced Cell Death (AICD) pathway whereas these tumor necrosis related proteins are expressed on self reactive b/t-cells and leads to apoptosis.

***if you have a defect in the Fas protein, you'll have Autoimmune Lympho--Proliferative Syndrome ALPS)***

Front 42

Normally, if a T-cell came in contact with a self-antigen, would the peripheral tolerance mechanism be...
a. an allergic response where the APC B-7 receptor interacted with the T-cells CTLA-4 receptor
b. an allergic reaction whereas the APC CTLA-4 interacted with the T-cells B7 receptor
c. an anergic reaction whereas the APC B7 interacted with the T-cells CTLA-4 receptor
d. an anergic reaction where the APC CTLA-4 interacted with the T-cells B7 receptor

Back 42

Answer is C

**ANERGIC MECHANISM**
**CTLA-4 is an INHIBITORY T-cell receptor**

Front 43

What cytokine and Gene do we need to adequately produce T-reg cells?

Back 43

1. Cytokine - IL-2
2. FOXp3 - Transcription factor that encodes for T-reg cells

**Mutation in FOXp3 leads to severe autoimmune disease (IPEX)

Front 44

What is the function of T-reg cells?

Back 44

1. To INHIBIT effector cells

Front 45

What is "receptor editing"?

Back 45

1. During central tolerance development of a B-cell, the screening process involves the same steps as in T-cell negative selection with 2 main differences... ONE - this process occurs in the Bone Marrow... TWO - before the B-cells undergo apoptosis due to high affintiy to self-antigen, they have the chance to switch their IgM light chain to one with a different variable regoin to "save their lives"... at this point they're released into the periphery as anergic cells

Front 46

What diseases result in defective B-cell and CD4 T-cell tolerance?

Back 46

1. Systemic Lupus Erythematosus (SLE)
2. Rheumatoid Arthritis