Final Exam Flashcards

1
Q

somatic recombination

A
  • recombination signal sequence (RSS) binds to RAG enzyme & directs enzyme to cut DNA between the gene segments
  • RSS’s flank every V, D, & J gene segment in a v controlled sequence (“12/23 rule”)
  • occurs in B cells & T cells
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2
Q

somatic hypermutation

A
  • the adaptive immune system’s way of evolving with the current pathogen that it’s faced with
  • the AID enzyme initiates an increased point mutation throughout the heavy- and light- chain V regions (not C regions) - this results in changes in the nucleotide sequence coding for CDR loops
  • occurs in B cells
    (Ig affinity maturation = somatic hypermutation + clonal selection)
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3
Q

isotope switching

A
  • aka “class switching”
  • DNA rearrangement that matches the rearranged V region with a new C region
    1. antigen binding of the antibody does not change
    2. function of the antibody molecule changes
    3. no junctional diversity
  • occurs in B cells
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4
Q

Correctly identify whether the following processes occur in T lymphocytes, B lymphocytes, neither, or both:

A

somatic recombination – Both B and T
junctional diversity – Both B and T
somatic hypermutation – B isotype switching - B
affinity maturation - B

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5
Q

positive selection

A
  • ensures that only T cells are able to bind to MHC 1 or 2 are released to the periphery
  • Double-Positive thymocytes undergo (+) selection in inner cortex of thymus - Only cells that are positively selected are allowed to continue their maturation.
  • determines if T cells are CD4+ or CD8+
  • occurs in αβ T cells only
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6
Q

negative selection

A
  • T cells: weeds out the cells that “bind too tightly” to self-antigens (γδ T cells don’t undergo negative selection)
  • immature αβ T cells undergo (-) selection in medulla of thymus
  • B cells: undergo “self-tolerance” in the bone marrow before getting secreted into secondary lymphoid tissue - immature B cell must not bind to any self-Ag (binds soluble self-Ag = anergy) (binds solid self-Ag = apoptosis)
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7
Q

two-signal hypothesis

A
  • T cell must receive a minimum of two signals from the APC to respond to antigen
  • on surface of naive T cell: TCR & CD28
  • on surface of APC: MHC-II & B7
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8
Q

linked recognition (aka cognate interaction)

A
  • Tfh cells activate naive B cells for antibody production - T cell and B cell must be specific for the same Ag (“linked recognition”)
    1. Tfh recognizes a peptide derived from the B cell’s antigen
    2. naive B cell and Tfh exchange signals that begin the process of B-cell activation (activates somatic hypermutation & affinity maturation)
  • CD40L on Tfh injects CD40 into B cell
  • cytokines secreted from Tfh bind to a BCR
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9
Q

CD4+ T cell effector phenotypes:
Th1

A

Th1
Cytokines that induce differentiation: IL-12, IFN-γ
Defining TF (Transcription Factor): T-bet
Characteristic cytokines: IL-2, IFN-γ
Function: Activate macrophages

Th2
Cytokines that induce differentiation: IL-4
Defining TF: GATA-3
Characteristic cytokines: IL-4, IL-5
Function: Activate cellular & antibody response to parasites

Th17
Cytokines that induce differentiation: IL-6, IL-21
Defining TF: RORγt
Characteristic cytokines: IL-17, IL-6
Function: Enhance neutrophil response to extracellular bacteria

Tfh
Cytokines that induce differentiation: IL-6, TGF-β, IL-21
Defining TF: Bcl6
Characteristic cytokines: IL-21
Function: Activate B cell maturation of antibody response

Treg
Cytokines that induce differentiation: TGF-β
Defining TF: FoxP3
Characteristic cytokines: TGF-β, IL-10
Function: Suppress other effector T cells, limits inflammation

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10
Q

CD4+ T cell effector phenotypes: Th17

A
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11
Q

CD4+ T cell effector phenotypes:
Th2

A
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12
Q

CD4+ T cell effector phenotypes:
Tfh

A
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13
Q

CD4+ T cell effector phenotypes:
Treg

A
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14
Q

The signature cytokines produced/secreted by:
Tc, Th1, Th2, Th17, Treg and Tfh cells

A

Type: Tc (Cytotoxic T Cells)
Cytokines:
- Cytotoxins (Perforin, Granzymes, Granulysin, Serglycin)
- Cytokines:
ING-gamma, LT, IL-2
Function: Kill virus-infected cells

Type: Th1 (T Helper 1 Cells)
Cytokines: IFN-γ, IL-2, TNF-α, LT
Function: Help macrophages to suppress intracellular infections

Type: Th2 (T Helper 2 Cells)
Cytokines: IL-4, IL-5, IL-10, IL-13, TGF-β
Function: Help basophils, mast cells, eosinophils, and B cells respond to parasite infections

Type: Tfh (Follicular Helper T Cells)
Cytokines: IL-21, IL-4, IFN-γ
Function: Help B cells become activated, switch isotype, and increase antibody affinity

Type: Th17 (T Helper 17 Cells)
Cytokines: IL-17, IL-21, IL-22, IL-26
Function: Enhance the neutrophil response to fungal & extracellular bacterial infections

Type: Treg (Regulatory T Cells)
Cytokines: TGF-β, IL-10, IL-35
Function: Suppress the activities of other effector T cell populations

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15
Q

Identify the cells which function as professional antigen-presenting cells and phagocytes.

A

antigen-presenting cells:
- B cells
- dendritic cells
- macrophages

phagocytes:
- macrophages

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16
Q

Identify the common CD markers used to identify human T cells (including subsets), B cells, and NK cells by flow cytometry.

A

B cells: CD19 or CD20

total T cells: CD3

T helper cells: CD3 + CD4

Tc cells: CD3 + CD8

NK cells: CD16 and/or CD56 (CD3 negative)

17
Q

Which cells express MHC-I & MHC-II?
What is the ultimate function of classical MHC molecules?

A

MHC-I:
- all nucleated cells except erythrocytes

MHC-II:
- all APCs (macrophage, DC, B cell)

TCRs can only recognize antigen if they are expressed within a MHC molecule

18
Q

Compare and contrast innate and adaptive immunity.

A

Innate Immunity

Response Time: Fast response (minutes to hours)
Function: Fixed function (does the same thing regardless of pathogen)
Specificity: Limited specificity
Adaptability: Constant during response, will not improve as infection lingers or with repeat exposure (does not adapt)
Adaptive Immunity

Response Time: Slow response (days to weeks)
Function: Variable (B/T cell antibodies react to specific pathogens)
Specificity: Specific and Selective
Adaptability: Body’s response improves with every exposure due to memory

19
Q

Compare and contrast active and passive immunity.

A

Active Immunity

Definition: The adaptive immune system is a subsystem of the overall immune system composed of highly specialized, systemic cells (B lymphocytes and T lymphocytes) and processes that eliminate or prevent pathogen growth.
Response Time: Much slower than innate immunity.
Characteristics: Has a variable ability to recognize pathogens from cell to cell, possesses numerous highly selective specificities, and improves during the immune response.

Passive Immunity
Definition: Passive immunity is the transfer of B cell immunity in the form of antibodies.
Occurrence: Can occur naturally (e.g., from mother to fetus via the placenta) or artificially (e.g., when antibodies that are specific to a pathogen or toxin are transferred to a person that is not immune, such as anti-venom for spider or snake bites).

20
Q

Compare and contrast primary and secondary immunity.

A

-Primary Immunity
Activation: B and T lymphocyte activation for first antigen exposure.

B Cell Development: Naive B cell becomes an antibody-producing plasma cell.

Antibodies: Production of low-affinity IgM antibodies.

-Secondary Immunity
Activation: Rapid and aggressive activation due to second exposure.

Regulation: Negative signal preventing naive B cell activation.

Memory Cells: Memory B cell binds pathogens to become antibody-producing plasma cell.

Antibodies: Production of high-affinity IgG antibodies.

21
Q

Compare and contrast cell-mediated and humoral immunity.

A

-Cell-Mediated Immunity
Antibodies: No antibodies are involved.

Cells: Involves phagocytes and antigen-specific cytotoxic T-lymphocytes.

Cytokines: Release various cytokines in response to antigens.

-Humoral Immunity
Antibodies: Antibody-mediated immunity by macromolecules.

B Lymphocyte Activation: The result of B lymphocyte activation.

22
Q

Compare and contrast B-1 and B-2 B cells.

A

-B-1 Cells
Location: Populates cavities (lungs, fetus, internal organs).

Function: Focus on tissue maintenance and repair.

Regeneration: Self-renewing.

Immunoglobulins: High spontaneous Ig production and IgM secretion.

Mutation Rate: Low somatic hypermutation.

Antigen Response: Responds to carbohydrate antigens.

-B-2 Cells
Presence: Only present after birth.

Origin: Replaced from bone marrow.

Immunoglobulins: Low Ig production but secretes IgG.

Mutation Rate: High levels of somatic hypermutation.

Antigen Response: Responds to lipids and proteins.

23
Q

Compare and contrast T-independent and T-dependent B cells responses.

A

-T-Dependent Response
Overall Response: T-dependent antigens refer to B-cell antigens that require T-cell help for proper response, accounting for more than 90% of responses.

Main Isotype Produced: Possible IgG (primarily B-2 B cells), but the body will produce whatever is needed to fight the pathogen.

Isotype Switching/Affinity Maturation: Involves isotype switching and somatic hypermutation (affinity maturation).

B Cell Activation: Ag-specific B cell activation.

Memory Response: Memory response induced.

-T-Independent Response
Overall Response: T-independent antigens cause B cell responses in the absence of T cell help, accounting for less than 10% of responses.

Main Isotype Produced: IgM (primarily B-1 B cells), with antibodies being low-affinity.

Isotype Switching/Affinity Maturation: No somatic hypermutation, with minimal isotype switching, meaning no affinity maturation occurs.

B Cell Activation: Polyspecific B cell activation.

Memory Response: No memory response induced.

24
Q

Compare and contrast αβ and γδ T cells.

A

90% αβ
10% γδ

-α:β T Cells
CD Expression: CD4 65%, CD8 35%

Target Antigens: Peptides presented by MHC-I or MHC-II molecules

TCR Junctional Diversity: Large

Abundance in Blood/Lymph: 70% of blood lymphocytes, little abundance in tissue

Overall Function: Adaptive immunity

-γ:δ T Cells
CD Expression: Mostly CD4- CD8-, around 70%

Additional CD Expression: CD8αα ~30% of gut intraepithelial lymphocytes (IEL)

Target Antigens: Self-proteins resembling MHC-I molecules and non-peptide small molecules presented by MHC-I-like and other cell-surface proteins

TCR Junctional Diversity: Small to medium

Abundance in Blood/Lymph: 5% of blood lymphocytes, big abundance in tissue

Overall Function: Tissue homeostasis of gut mucosal endothelium

25
Q

Describe the structures of the BCR and TCR

A

-BCR (B-Cell Receptor)
Structure: Heterotetrametric (2 heavy and 2 light chains)

Antigen Binding Sites: 2

Antigen Specificity: Binds to proteins, glycoproteins, lipoproteins

Signaling Molecules: Associated with Igα & Igβ signaling molecules (cannot signal on its own in response to antigen binding)

Somatic Recombination: Occurs in the bone marrow

-TCR (T-Cell Receptor)
Structure: Heterodimer (1 TCRα & 1 TCRβ chain)

Antigen Binding Sites: 1

Antigen Specificity: Binds to peptide fragments in MHC

Co-Receptors and Signaling: Associated with CD4 or CD8 co-receptors and CD3 signaling complex

Somatic Recombination: Occurs in the thymus

26
Q

List:
- the five main antibody isotypes
- their main characteristics
-> the FcR they bind to

A

IgG:
- most abundant in serum & body fluids
- can cross placenta
- neutralization
- opsonization
- sensitize for NK killing
- bind (fix) complement
-> FcɣRI, FcɣRIIA, FcɣRIIB2, FcɣRIIB1, FcɣRIII

IgE:
- sensitize mast cells
-> FcεRI

IgA:
- highest concentration in mucus (dimer)
- monomer is found in blood
- neutralization
-> FcαR1

IgM:
- the biggest (molecular weight)
- pentamer
- bind (fix) complement

IgD:
- primarily found in respiratory tract

IgG, IgA, & IgM compose 99% of all antibody in blood/body fluids

27
Q

List the ultimate function(s) of each FcR

A

Phagocytosis: FcɣRI, FcɣRII-A, FcαR1

Inhibitory: FcɣRII-B1, FcɣRII-B2

Granule exocytosis: FcεRI

ADCC: FcɣRIII - otherwise known as CD16

28
Q

Identify the molecules that lead to formation of C3 convertases (in order of binding/activation), the C3 and C5 convertases and the MAC of the 3 pathways of complement activation.

A

C3 convertase:
- alternative: iC3Bb & C3bBb
- classical & lectin: C4b2a

C5 convertase: (just add 3b)
- alternative: C3bBb3b
- classical & lectin: C4b2a3b

C5 activation by alternative C5 convertase creates MAC (C5-C9)

29
Q

List primary and secondary lymphoid tissues.

Describe the general characteristics of secondary lymphoid tissues and why this is essential for efficient adaptive immune responses.

A

primary: thymus & bone marrow
secondary: (primarily) lymph nodes & spleen

Secondary lymphoid tissue: maintain mature naïve lymphocytes and initiate an adaptive immune response
- naive T cell interacts with APC in secondary tissue & induces T cell activation
- GALT, BALT, MALT

30
Q

For serology testing, identify the usefulness of specific detection of antigen versus antibody.

A

serology:
- study of non-cellular components in blood (serum)
- for infectious disease in which the organism isn’t easily cultured, this means:
“detection of pathogen antigen or host antibody to the pathogen”

31
Q

For antibody detection, identify the significance of specific detection of IgM, IgG or IgE isotypes of antibody for either immune response staging or categorization.

A

IgM: Indicates a current or recent infection

IgG: Indicates a current or past infection with some sort of immunity present

IgE: Indicates an allergic response or a parasitic infection