Immunologie-P1 Flashcards

1
Q

T cells monitor _____ compartments (intracellular/extracellular) for antigens derived from pathogens.

A

intracellular

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2
Q

What are the 2 major subsets of T cells, based on cell surface expression of __ and ___ co-receptors?

A
CD4+ = helper T cells
CD8+ = cytotoxic T lymphocytes
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3
Q

Do T cells recognize native antigen?

A

NO.

They must first see peptide Ag presented by MHC molecules on APC cells.

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4
Q

What are the professional APCs?

A
  1. Dendritic cells
  2. Macrophages
  3. B cells
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5
Q

What is the TCR (T cell receptor) composed of?

A

1 alpha chain

1 beta chain

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6
Q

How do T cells only recognize foreign antigens?

A

Thymus deletes T cells that respond to self-antigens, so this results in having mature T cells that are specific for FOREIGN antigens.

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7
Q

Which parts of the TCR interact directly w/both MHC molecules and peptide antigens presented by MHC molecules?

A

Hypervariable regions of TCR (alpha and beta chains)

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8
Q

How is TCR generated randomly through DNA rearrangement?

A

You select “Cassetes” (different snippets of different alleles) on each gene (A and B). Recombination occurs and the DNA is rearranged. It undergoes transcription, splicing, and translation.

Process of recombination occurs with recombinase gene. (deficiency in recombinase = no T Cell receptors)

Once it is recombined, then you have copies of that TCR. Set. Then clonal expansion.

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9
Q

How does the TCR engage peptide:MHC complexes presented by APC?

A
  • hypervariable region (part of alpha and beta chains) interact directly with peptide:MHC complex. The alpha and beta chains recognize the antigen in the context of the MHC molecule. So alpha and beta chains recognize the POLYMORPHIC regions of the MHC molecules.
  • Once the TCR binds the peptide:MHC complex, CD8 and CD4 co-receptors engage the NONpolymorphic regions of MHC I and MHC II, respectively.
  • There is also a complex of proteins associated with the TCR, called a complex w/CD3 and zeta chain proteins. These, along with the TCR, form the TCR COMPLEX.

When the TCR binds to MHC:peptide complex, it induces T cell signaling through CD3 and zeta chain proteins. These form Signal 1. - crucial for T cell priming.

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10
Q

What is Signal 1?

A

Induced T cell signaling through CD3 and zeta chain. This occurs once…

(1) the TCR binds the peptide:MHC complex through the alpha and beta chains recognizing the polymorphic regions of the MHC molecule.
(2) the CD4 and CD8 co-receptors engage with the NONpolymorphic regions of MHCI and II.
Then (3) you have induced T cell signaling. Signal 1.

remember this is a respective process (CD4 T cell vs. CD8 T cell).

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11
Q

What is the involvement of CD4 and CD8 co-receptors in antigen recognition by T cells?

A
  • CD4 and CD8 are NOT co-stimulators. They are co-receptors that stabilize binding.
  • CD3: important for signaling
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12
Q

What is Signal 2?

A
  • Signal 2 = costimulation.
  • It is produced by interaction between B7 (on the APC) and CD28 (on the T-cell).
  • B7 is only expressed by professional APCs that have recently been activated/matured.
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13
Q

What happens if a T cell encounters a peptide:MHC on a cell that is not a professional APC?

A
  • They receive Signal 1, but not Signal 2.
  • Leads to anergy (T cell inactivation).
  • This prevents T cells that may recognize self-antigens from attacking uninfected tissues.
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14
Q

How does a Th cell (CD4) get activated?

A
  1. Foreign body gets phagocytosed and is presented on MHC Class II molecule.
  2. It is recognized by TCR on Th cell (Signal 1)
  3. Costimulatory signal given by interaction of B7 (on APC) and CD28 (on Th) [Signal 2].
  4. Th cell is activated to produce cytokines.
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15
Q

How does a CTL (CD8 cell) get activated?

A
  1. Endogenously synthesized (viral or self) proteins presented on MHC I and recognized by TCR on CTL.
  2. IL-2 from Th cell activates the CTL to kill the virally-infected cell.
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16
Q

What are examples of other costimulatory molecules?

A
  • B7-1 : CD28 *Note - B7-1 is also called CD80
  • B7:2 : CD28 *Note - B7-2 is also called CD86
  • B7-1 / B7-2 : CTLA-4 –> this is a suppressor. Competes against CD28.
  • ICAM-1 : LFA-1 (adhesion)
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17
Q

B7-1 is also called…

A

CD80

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18
Q

B7-2 is also called…

A

CD86

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19
Q

What is the purpose of inducing anergy?

A

Anergy = T-cell inactivation

Purpose: to make sure that the T-cell won’t respond to self-antigens (prevent T-cells that may recognize a self-antigen from attacking uninfected tissues).

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20
Q

What circumstances lead to peripheral tolerance?

A

Peripheral tolerance is when T-cells encounter self-antigen. Because there is no costimulation, anergy is induced, and the T-cells remain inactive.

On the other hand, if a T- cell is stimulated by an infected professional APC, it would see both signals. Then if it saw this antigen on an epithelial cell, it would be activated to kill this infected epithelial cell.

21
Q

How do integrins help form the immunological synapse?

A
  1. When a T-cell recognizes an antigen-presenting cell, it initially binds due to the integrins (integrin on T-cell binds to ligand on APC).
  2. Then, when the TCR binds to the peptide:MHC complex, this activates the integrins.
  3. The APC is then stimulated to produce chemokines (sml chemotactic molecules).
  4. The chemokines help recruit and activate integrins.
  5. The integrins cluster together, increasing the affinity of the integrins.
  6. This leads to a stronger T-cell:APC adhesion, creating the immunological synapse.
  7. Increases the T-cell response by recruiting additional MHC molecules and TCR’s into the synapse – they can interact for a longer period of time.
22
Q

What is a cytokine, and who makes it?

A
  • Small protein molecule that is used in cellular communication, often in immunomodulatory molecules.
  • Made by all types of immune cells, also by other cells in the body
23
Q

What is the role of IL-2 in T-cell activation?

A

1) When a TCR binds to a peptide:MHC complex and receives costimulation, the TC produces IL-2. CD4 cells predominantly produce IL-2, but CD8 cells can also produce it.
2) The IL-2 will bind to IL-2 receptor on its own cell (TC)
3) This causes the cell to proliferate –> clonal expansion.

  • IL-2 acts both in an autocrine and paracrine fashion.
  • All T-cells constitutively express the low-affinity IL-2 receptor, but upon activation, they begin expressing the high affinity IL-2R, which gives them a better ability to respond to IL-2.
24
Q

What is the inhibitory function of CD28- CTLA4 interactions?

A

1) When the T-cell becomes activated (TCR binds cognate peptide:MHC complex and costimulation occurs), it starts expressing CTLA-4.
* CTLA-4 is an inhibitory molecule.

2) CTLA-4 also binds B7 (CD80 or CD86). It binds B7 more avidly than does CD28. So it outcompetes CD28.
3) The T-cells receive an INHIBITORY signal –> this can dampen or terminate the T-cell response.

Purpose: to control T-cell activation after infection has been cleared.

25
Q

How do bacterial super-antigens activate T-cells in a non-specific manner?

A
  • The superantigen interacts w/the variable region on the B-chain of the TCR. –> leads to antigen-non-specific T-cell activation.
  • Since the superantigen binds to ALL TCR’s, it leads to polyclonal activation
  • Activates 80% of total T-cell compartmente (compared to how a peptide:MHC complex might activate 0.001% of body’s T-cells)
  • The super-antigen-activated T-cells release lots of cytokines –> huge immunological cascade.
26
Q

What are super-antigens?

A

A class of antigens, often derived from bacteria, that cause non-specific activation of T-cells.

27
Q

In the thymus, is there a ___ (high or low) rate of death of T cells?

A

high rate.

So only a few of the double + T thymocytes will mature to single positive T cells that express EITHER CD4+ or CD8+.

28
Q

What is positive selection in the thymus?

A

When the T-cells are selected for those that do bind MHC-self-peptide. Those that cannot bind to its selecting element (MHC + self-peptide) will die from neglect (the T cell needs signaling from the TCR to express survival genes).

29
Q

Which cells are responsible for + selection?

A

Thymic epithelial cells in the cortex (“nurse cells”)

30
Q

What is negative selection in the thymus?

A

T-cells are selected based on whether their TCR binds TOO STRONGLY to MHC Class I:peptide or MHC Class 2:peptide complexes.
If they bind too strongly, they might be autoreactive (activated by self-Ag and would cause autoimmunity). These are induced to die.

31
Q

Where does negative selection in the thymus occur?

A

medulla or medullary-cortical junction

32
Q

What is AIRE?

A

transcriptional regulator, allows expression of “non” thymic genes that provide peptides for MHC I molecules and thus negative selection.

33
Q

Tolerance

A

The host is tolerant of their own tissue antigens.

34
Q

Central tolerance

A

Self-reactive T cells are clonally deleted in the thymus (primary lymphoid tissue).

35
Q

Peripheral tolerance

A

Autoreactive T cells sometimes escape deletion in the thymus and migrate to the periphery. But they recognize self-antigen on non-APCs, so these T-cells don’t get costimulation for presentation. So they are not activated to respond.

36
Q

What is ignorance?

A

Autoreactive T cells not activated in tissues where they are excluded (where the naive T cells don’t routinely circulate - like testes, epidermis).

37
Q

What is anergy?

A

Autoreactive T cells that engage peptide:MHC won’t be responsible when they do not have co-stimulation (when they are not on an APC).

38
Q

Regulatory T cells express what?

A

CD4
CD25 (IL-2 receptor)
Foxp3 transcription factor

39
Q

What are regulatory T cells involved in?

A
  • normal process of immune shutdown after antigen has been eliminated
  • suppression of autoreactive T cells
40
Q

What is affinity maturation?

A

A B cell’s repeated exposure to a protein antigen results in the production of antibodies with increasing affinity for the antigen. Leads to production of Ab with improved capacity to bind to and neutralize microbes and their toxins.

41
Q

What is isotype switching?

A

This is when some B cells, when they are being differentiated, begin to produce antibodies of different heavy-chain isotypes (classes). These are then specialized to fight different types of microbes.

42
Q

What are the 2 classes of membrane-bound antibodies that naive B cells express?

A

IgM and IgD

43
Q

What are the phases of the humoral immune response?

A
  1. Naive B-cells with IgM+, IgD+ recognize antigens.
  2. W/the help of helper T cells (CD4+), the B cells become activated to proliferate.
  3. They give rise to clonal expansion.
  4. The activated B cells differentiate into antibody-secreting plasma cells.
  5. Some of the activated B cells undergo heavy-chain isotype switching and affinity maturation.
44
Q

Protein antigens are processed and presented by ______ and recognized by _______.

A
  • Protein Ag processed/presented by APCs (macrophages, dendritic cells)
  • Protein Ag recognized by helper T cells.
45
Q

What are T-dependent antibody responses vs. T-independent antibody responses?

A
  • T dependent antibody responses: protein antigens and the antibody responses to these antigens
  • T independent antibody responses: nonprotein antigens and the antibody responses to them. Ex: polysaccharides, lipids, other non-proteins.
46
Q

Antibodies produced in response to protein antigen show _______ (more or less) isotype switching and affinity maturation?

A

more isotype switching and affinity maturation –> so most specialized responses generated under influence of helper T cells.

47
Q

What type of antibody response do follicular B cells make?

A

They make up most of the T-dependent, class-switched, high-affinity Ab responses to protein antigens.

Give rise to plasma cells

Live in/circulate through follicles of lymphoid organs.

48
Q

What is the difference between primary antibody response and secondary Ab response?

A
  1. Lag after immunization: Primary = 5-10 days; Secondary = 1-3 days
  2. Peak response: Primary = smaller; Secondary = larger
  3. Antibody isotype: Primary: IgM > IgG. secondary: Relative increase in IgG (or in some situations, IgA or IgE)
  4. Ab affinity: Primary response = lower average affinity, more variable. Secondary = higher average affinity (affinity maturation)
49
Q

Describe a secondary response in terms of isotype switching and affinity maturation.

A

Increased isotype switching and affinity maturation - b/c repeated stimulation by a protein Ag would lead to an increase in # and activity of helper T cells.