Final Exam Flashcards
somatic recombination
- 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
somatic hypermutation
- 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)
isotope switching
- 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
Correctly identify whether the following processes occur in T lymphocytes, B lymphocytes, neither, or both:
somatic recombination – Both B and T
junctional diversity – Both B and T
somatic hypermutation – B isotype switching - B
affinity maturation - B
positive selection
- 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
negative selection
- 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)
two-signal hypothesis
- 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
linked recognition (aka cognate interaction)
- 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
CD4+ T cell effector phenotypes:
Th1
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
CD4+ T cell effector phenotypes: Th17
CD4+ T cell effector phenotypes:
Th2
CD4+ T cell effector phenotypes:
Tfh
CD4+ T cell effector phenotypes:
Treg
The signature cytokines produced/secreted by:
Tc, Th1, Th2, Th17, Treg and Tfh cells
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
Identify the cells which function as professional antigen-presenting cells and phagocytes.
antigen-presenting cells:
- B cells
- dendritic cells
- macrophages
phagocytes:
- macrophages
Identify the common CD markers used to identify human T cells (including subsets), B cells, and NK cells by flow cytometry.
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)
Which cells express MHC-I & MHC-II?
What is the ultimate function of classical MHC molecules?
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
Compare and contrast innate and adaptive immunity.
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
Compare and contrast active and passive immunity.
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).
Compare and contrast primary and secondary immunity.
-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.
Compare and contrast cell-mediated and humoral immunity.
-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.
Compare and contrast B-1 and B-2 B cells.
-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.
Compare and contrast T-independent and T-dependent B cells responses.
-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.
Compare and contrast αβ and γδ T cells.
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
Describe the structures of the BCR and TCR
-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
List:
- the five main antibody isotypes
- their main characteristics
-> the FcR they bind to
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
List the ultimate function(s) of each FcR
Phagocytosis: FcɣRI, FcɣRII-A, FcαR1
Inhibitory: FcɣRII-B1, FcɣRII-B2
Granule exocytosis: FcεRI
ADCC: FcɣRIII - otherwise known as CD16
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.
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)
List primary and secondary lymphoid tissues.
Describe the general characteristics of secondary lymphoid tissues and why this is essential for efficient adaptive immune responses.
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
For serology testing, identify the usefulness of specific detection of antigen versus antibody.
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”
For antibody detection, identify the significance of specific detection of IgM, IgG or IgE isotypes of antibody for either immune response staging or categorization.
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
