Immunobio lectures 9-13 Flashcards

1
Q

What are the hallmark features of immunological memory?

A

Longevity, rapid and robust response upon re-exposure, stemness (self-renewal), and enhanced effectiveness compared to the primary immune response.

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2
Q

What is the role of immunological memory in vaccination?

A

Vaccines aim to induce immunological memory so that upon real infection, the immune system can respond rapidly and effectively, often preventing disease.

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3
Q

What type of antigen typically triggers a T-independent B cell response, and what is the resulting antibody?

A

Multivalent non-protein antigens (e.g., polysaccharides) trigger a T-independent response, producing mainly low-affinity IgM antibodies.

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4
Q

What type of antigen elicits a T-dependent B cell response and why is T cell help crucial?

A

Protein antigens elicit T-dependent responses. T cell help (via CD40L and cytokines) is crucial for class switching, affinity maturation, and memory formation.

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5
Q

How do B and T cells interact during a T-dependent response?

A

B cells present antigen via MHC II to T cells, leading to CD40-CD40L interaction and cytokine signaling, activating B cells for proliferation and differentiation.

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6
Q

What signals are necessary for B cell isotype class switching?

A

CD40-CD40L interaction and cytokines (e.g., IL-4, IFN-γ) from helper T cells guide the switch to specific antibody isotypes.

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7
Q

What are the functional roles of different antibody isotypes (IgG, IgA, IgE)?

A

IgG: Neutralization, opsonization, complement activation; IgA: Mucosal immunity; IgE: Defense against parasites, allergy mediator

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8
Q

What two zones exist in the germinal center and what occurs in each?

A

Dark Zone: B cell proliferation and somatic hypermutation; Light Zone: Affinity selection via follicular dendritic cells (FDCs) and T follicular helper (TFH) cells

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9
Q

What is somatic hypermutation and where does it occur?

A

It’s the process of introducing point mutations in variable regions of BCR genes to increase antigen affinity. It occurs in the dark zone of the germinal center.

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10
Q

How are high-affinity B cells selected in the germinal center?

A

B cells compete for antigen on FDCs and T cell help; only those with high-affinity receptors receive survival signals and differentiate further.

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11
Q

What is the difference between long-lived plasma cells and memory B cells?

A

Plasma Cells: Secrete antibodies for extended periods (often in bone marrow); Memory B Cells: Quiescent, rapid responders upon antigen re-exposure

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12
Q

How do primary and secondary antibody responses differ?

A

Primary: Slower, lower magnitude, mostly IgM; Secondary: Faster, higher magnitude, mostly high-affinity IgG (or IgA/IgE)

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13
Q

What are the three major subsets of memory CD8+ T cells?

A

Central Memory (T_CM), Effector Memory (T_EM), Resident Memory (T_RM)

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14
Q

Where are T_CM cells located and what is their main role?

A

Found in secondary lymphoid organs; they proliferate upon antigen re-exposure and can generate new effector T cells.

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15
Q

What is the functional characteristic of T_EM cells?

A

They circulate through peripheral tissues and rapidly exert effector functions like cytotoxicity upon encountering antigen.

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16
Q

What distinguishes T_RM cells from other memory T cells?

A

T_RM cells are non-circulating and permanently reside in tissues (e.g., skin, mucosa), providing rapid local protection at entry points.

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17
Q

What cytokines maintain memory T cells in the absence of antigen?

A

IL-7 and IL-15 are critical for the long-term maintenance and homeostatic proliferation of memory T cells.

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18
Q

What is the role of follicular dendritic cells (FDCs) in the germinal center?

A

FDCs present native antigen to B cells in the light zone, allowing selection based on receptor affinity.

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19
Q

What is the role of T follicular helper (TFH) cells in B cell memory formation?

A

TFH cells provide essential survival and differentiation signals (via CD40L and cytokines) that drive affinity maturation and memory/plasma cell fate.

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20
Q

Why is memory B cell response faster and more robust than naïve B cell response?

A

Memory B cells have undergone prior selection and affinity maturation, allowing for quicker activation and production of high-affinity, class-switched antibodies.

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21
Q
A
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22
Q

What are cytokines?

A

Low-molecular-weight proteins produced by one cell that act on itself or another cell by binding to surface receptors; regulate immune responses.

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23
Q

Are cytokines stored in cells before use?

A

No. They are rapidly synthesized and released after stimulation; gene transcription is transient and mRNA is unstable to limit synthesis.

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24
Q

How do cytokines exert their effects?

A

By binding to specific membrane receptors made of one or more transmembrane proteins with extracellular domains for binding and intracellular tails for signaling.

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25
What are the major types of cytokines?
Interleukins (IL-1 to IL-37), Interferons (IFNs), Tumor Necrosis Factors (TNF), and growth factors (e.g., GM-CSF).
26
How are cytokines categorized based on source?
Lymphokines (from lymphocytes), monokines (from monocytes/macrophages), and by function: innate vs. adaptive.
27
What are key mechanisms that regulate cytokine activity?
Regulated receptor expression, short half-life in body fluids, and need for proximity to establish concentration gradients.
28
What are common properties of cytokines?
Pleiotropism, redundancy, synergy, and antagonism.
29
What are the 3 functional categories of cytokines?
1) Mediators/regulators of innate immunity, 2) Mediators/regulators of adaptive immunity, 3) Stimulators of hematopoiesis.
30
Which cytokines are key in innate immunity?
IL-12, TNF, IL-1, IL-6, and type I interferons.
31
Which cytokines are key in adaptive immunity?
IFN-γ (type II IFN) and IL-4.
32
What are the types and roles of interferons?
Type I (α, β, etc.): antiviral; Type II (γ): phagocyte activation; Type III (λ): antiviral. Type I and III made by tissue/innate cells, Type II by lymphocytes.
33
What is the function of IFN-γ?
Activates phagocytes, upregulates MHC I & II, induces antimicrobial substances like nitric oxide.
34
What stimulates TNF production?
Primarily LPS from bacteria. Produced by macrophages, DCs, Th1 cells, and others.
35
What are TNF's local functions?
Recruits neutrophils/monocytes, activates endothelial cells, induces IL-1, enhances integrin affinity, helps DC migration.
36
What are TNF's systemic effects?
Fever (via hypothalamus), acute-phase protein production (liver), cachexia (muscle/fat wasting).
37
How does TNF cause septic shock?
High levels reduce myocardial contractility, induce intravascular thrombosis, and cause metabolic issues like hypoglycemia.
38
What are chemokines?
Chemotactic cytokines that guide leukocyte migration; classified into CC, CXC, C, and CX3C families.
39
What induces chemokine production?
Microbial products and cytokines like IL-1, IL-17, and TNF.
40
How do chemokines affect leukocytes?
They increase motility, are required for DC migration to lymph nodes, and recruit leukocytes into tissues.
41
What role do chemokines play in HIV?
CCR5 and CXCR4 chemokine receptors act as co-receptors for HIV entry into cells.
42
How do integrins respond to chemokines?
Chemokines activate integrins, increasing their affinity for ligands and mediating cell adhesion.
43
Describe leukocyte recruitment into tissues.
Multistep: selectin-mediated rolling, chemokine-induced integrin activation, firm adhesion, transmigration.
44
What is the role of chemokines in lymphoid tissue organization?
They guide positioning of lymphocyte populations, e.g., CCL21 attracts naïve T cells via CCR7.
45
What are the two major types of killer lymphocytes?
Cytotoxic T lymphocytes (CTLs, CD8+) and Natural Killer (NK) cells
46
What are the main functions of killer lymphocytes?
Kill infected or tumor cells and secrete cytokines like IFN-γ
47
What activates CD8+ T cells?
Antigen presentation by dendritic cells on MHC I in peripheral lymphoid organs
48
What are the effector functions of CD8+ T cells?
Direct cytotoxicity (killing infected/tumor cells) and cytokine production
49
What molecules do CTLs use to kill target cells?
Perforin and granzymes (mainly granzyme B), and Fas ligand (FasL)
50
What is the role of perforin?
Facilitates delivery of granzymes into target cells by disrupting membranes
51
What is the role of granzyme B?
Activates caspases to induce apoptosis
52
How do CTLs avoid self-damage during killing?
Targeted granule release and protective enzyme cathepsin B degrades stray perforin
53
Name the two mechanisms used by CTLs to kill target cells.
1. Granule-mediated apoptosis (perforin + granzymes), 2. Fas–FasL interaction (activates caspases)
54
Which method is dominant in CTL-mediated killing?
Perforin and granzyme B pathway
55
Which cytokine is primarily produced by CD8+ T cells?
Interferon gamma (IFN-γ)
56
What is the role of CD8+ derived IFN-γ?
Activates macrophages, aids in microbe clearance, and contributes to inflammation
57
What is unique about NK cell activation?
They kill without needing antigen-specific priming (natural response)
58
What are the key functions of NK cells?
Early defense against viruses, tumor surveillance, and IFN-γ production
59
What are the two main ways NK cells recognize targets?
1. Missing-self (loss of MHC I on target), 2. Stress-induced self (upregulation of activating ligands)
60
What receptors regulate NK cell activation?
Inhibitory receptors (detect MHC I) and activating receptors (detect stress or antibody)
61
What molecules do NK cells use to kill?
Perforin and granzymes, like CTLs
62
What is ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity)?
NK cells recognize antibody-coated cells via FcγRIII (CD16) and kill them
63
How do NK cells contribute to the adaptive immune response?
By producing IFN-γ, which enhances macrophage function and shapes T cell responses
64
What is the main difference between CTL and NK cell recognition?
CTLs recognize specific antigens via TCR + MHC I; NK cells recognize absence or stress signals
65
What is the 'lytic hit'?
The delivery of cytotoxic granule proteins (perforin + granzymes) to a target cell
66
What types of antigens can B cells recognize?
B cells can recognize native antigens, including whole proteins, carbohydrates, lipids, nucleic acids, and peptides.
67
What types of antigens can T cells recognize?
T cells can only recognize peptide antigens that are presented on MHC molecules.
68
What is the role of Antigen Presenting Cells (APCs)?
APCs are the link between innate and adaptive immunity, presenting antigens to T cells.
69
What are the 4 steps of T cell activation?
1. Antigen recognition 2. Activation 3. Clonal expansion 4. Differentiation
70
What is the immunological synapse?
A structured interface between a T cell and an APC where signaling occurs during activation.
71
What is the two-signal hypothesis for T cell activation?
Signal 1: TCR binds to MHC-peptide complex Signal 2: Co-stimulatory molecules are engaged
72
What happens if TCR engages MHC-peptide without co-stimulation?
The T cell may become anergic (unresponsive) or undergo apoptosis.
73
What is cross-presentation?
It is when exogenous antigens are presented on MHC class I molecules, allowing activation of CD8+ T cells.
74
What are the co-stimulatory molecules involved in T cell activation?
CD28 on T cells binding to B7 molecules (CD80/86) on APCs.
75
Why is T cell activation tightly regulated?
To prevent inappropriate immune responses and ensure activation only occurs in the presence of pathogens.
76
What are the two main subsets of CD4+ T helper cells discovered by Mosmann and colleagues in 1986?
Th1 and Th2
77
What cytokines are secreted by Th1 cells?
IFN-γ and IL-2
78
What cytokines are secreted by Th2 cells?
IL-4, IL-5, and IL-13
79
What transcription factor drives Th1 differentiation?
T-bet (TBX21)
80
What innate cytokine promotes Th1 development?
IL-12
81
What transcription factor drives Th2 differentiation?
GATA-3
82
What innate cytokine promotes Th2 development?
IL-4
83
Which CD4+ T cell subset is involved in defense against intracellular pathogens?
Th1
84
Which CD4+ T cell subset is involved in defense against helminths and allergic responses?
Th2
85
What is the main effector function of IFN-γ in Th1 responses?
Activates macrophages to kill intracellular microbes
86
What is the role of IL-4 in Th2 responses?
Stimulates B cell class switching to IgE and promotes eosinophil recruitment
87
What kind of macrophage is activated by Th1 cells?
Type I macrophage (M1)
88
What kind of macrophage is activated by Th2 cells?
Type II macrophage (M2)
89
How do CD4+ T cells help B cells?
By providing cytokines and co-stimulatory signals that promote class switching and affinity maturation
90
What experiment showed the functional dichotomy between Th1 and Th2 cells?
Leishmania major infection in BALB/c (susceptible, Th2-dominant) vs. C57BL/6 (resistant, Th1-dominant) mice
91
What are the implications of the Th1/Th2 paradigm in disease?
Explains susceptibility/resistance to infections and the pathogenesis of autoimmune and allergic diseases
92
What does T-bet overexpression in Th2 cells cause?
Switches them to a Th1-like phenotype with IFN-γ production
93
What does GATA-3 overexpression in Th1 cells cause?
Switches them to a Th2-like phenotype with IL-4 production
94
What is the primary source of antigen for CD4+ T cells?
Exogenous antigens presented on MHC class II
95
Why is co-stimulation important in T cell activation?
It ensures that T cells respond only to foreign antigens in the presence of danger signals