post-transcriptional control of gene expression pt1

Question 1

What determines T cell survival during selection?

Answer 1

TCR affinity for self-MHC:
Low affinity: T cells die by neglect.
High affinity: T cells undergo negative selection.
Intermediate affinity: T cells survive and are positively selected.

Question 2

What are Tregs, and how do they arise?

Answer 2

Regulatory T cells (Tregs) suppress immune responses and prevent autoimmunity.
nTreg: Develop in the thymus from high-affinity self-reactive T cells.
iTreg: Induced in peripheral tissues.

Question 3

What mechanisms ensure B cell tolerance?

Answer 3

Clonal deletion: Self-reactive B cells are deleted in the bone marrow.
Receptor editing: Self-reactive immature B cells can rearrange light chain genes to remove self-reactivity.
Anergy: Self-reactive B cells become unresponsive if they encounter non-multivalent self-antigens.

Question 4

What happens to self-reactive immature B cells in the bone marrow?

Answer 4

They are deleted, undergo receptor editing, or become anergic before entering circulation.

Question 5

What role do Tregs play in immune regulation?

Answer 5

Tregs secrete suppressive cytokines (TGF-β, IL-10) and suppress other T cell responses via cell-cell contact or cytokine inhibition

Question 6

What are Bregs, and what do they do?

Answer 6

Regulatory B cells (Bregs) secrete IL-10, playing a crucial role in preventing autoimmunity.

Question 7

Why are there multiple CD4+ T cell subsets?

Answer 7

To tailor immune responses to specific pathogens and regulate them effectively.

Question 8

Name the functions of different CD4+ T cell subsets.

Answer 8

TH1: Activate macrophages and cytotoxic T cells.
TH2: Promote eosinophil and mast cell responses, especially IgE antibody responses.
TH17: Recruit neutrophils for fungal infections, linked to autoimmunity.
Treg: Suppress unwanted immune responses.
TFH: Help B cells in germinal centers.

Question 9

What determines CD4+ T cell polarization?

Answer 9

Cytokines present during activation influence differentiation:
- IL-12, IFN-γ → TH1.
- IL-4 → TH2.
- TGF-β, IL-10 → Treg.
- IL-6, IL-23 → TH17.

Question 10

Where does clonal deletion of T cells occur?

Answer 10

In the thymus.

Question 11

Where does clonal deletion of B cells occur?

Answer 11

In the bone marrow

Question 12

What happens to immature B cells that recognise self-antigens but are not deleted?

Answer 12

They undergo receptor editing or become anergic.

Question 13

What do Tregs express, and what is their role?

Answer 13

Tregs express FoxP3 and suppress immune responses to prevent autoimmunity

Question 14

What cytokines do Tregs secrete?

Answer 14

TGF-β and IL-10.

Question 15

How do iTregs differ from nTregs?

Answer 15

iTregs are induced in periperhal tissues, whereas nTregs develop in the thymus.

Question 16

Why is it essential to understand specific features of pathogens?

Answer 16

To identify their entry sites, target cells/tissues, evasion mechanisms, life cycles, and their impact on the immune system.

Question 17

Name four types of organisms that may cause disease.

Answer 17

Bacteria, viruses, fungi, parasites (including worms and protozoa).

Question 18

What are the main points to consider in immune responses against infections?

Answer 18

Different infections require different effector mechanisms.
Outcome depends on the type of immune response.
Pathogens evolve ways to escape host defenses.
The immune response can contribute to disease symptoms.

Question 19

What are the two types of host defense mechanisms?

Answer 19

Innate Defense Mechanisms: Rapid, non-specific, act as the first line of defense.
Acquired/Adaptive Defense Mechanisms: Slower, exhibit memory, and enhance innate defenses.

Question 20

Describe the roles of different CD4+ T helper cells.

Answer 20

TH1: Active against intracellular pathogens; activate macrophages and cytotoxic T cells.
TH2: Active against extracellular pathogens; support antibody production and activate eosinophils, basophils, and mast cells.
TH17: Active against extracellular bacteria and fungi; attract neutrophils.

Question 21

Give examples of Gram-positive and Gram-negative bacteria.

Answer 21

Gram-positive: Staphylococcus aureus, Streptococcus spp.
Gram-negative: Salmonella, Neisseria, Shigella.

Question 22

What immune responses are triggered by bacterial cell wall components like LPS and peptidoglycan?

Answer 22

They bind to Toll-like receptors (TLRs), promoting inflammation, dendritic cell maturation, and T/B cell activation.

Question 23

What roles do antibodies play in bacterial infection defense?

Answer 23

1. Opsonization.
2. Complement activation.
3. Neutralizing toxins.
4. Preventing mucosal adherence of bacteria.

Question 24

What is the importance of complement in bacterial infections?

Answer 24

Lyses Gram-negative bacteria via the membrane attack complex (MAC).
Promotes inflammation and phagocytosis.

Question 25

Name a bacterium that survives within phagocytes and its mechanism.

Answer 25

Mycobacterium tuberculosis inhibits lysosome/phagosome fusion.

Question 26

Describe the two immune response outcomes in Mycobacterium leprae infection.

Answer 26

Tuberculoid leprosy: Strong TH1 response; granulomas, slow progression.
Lepromatous leprosy: Strong TH2 response; disseminated infection, high fatality.

Question 27

What determines whether TH1 or TH2 cytokines dominate in leprosy?

Answer 27

TH1 cytokines: IL-2, IFNγ.
TH2 cytokines: IL-4, IL-5, IL-10.

Question 28

What are Toll-like receptors (TLRs) and their role?

Answer 28

TLRs are pattern recognition receptors (PRRs) that bind pathogen-associated molecular patterns (PAMPs), promoting inflammation, dendritic cell maturation, and adaptive immune activation.

Question 29

What kind of infections is the MAC particularly useful for?

Answer 29

Gram-negative bacterial infections.

Question 30

Why can the same pathogen cause different clinical outcomes (e.g., M. leprae)?

Answer 30

Outcomes depend on the dominant immune response type (TH1 vs. TH2).

Question 31

What are granulomas, and what pathogen is commonly associated with them?

Answer 31

Granulomas are organized immune cell structures, often associated with Mycobacterium infections (e.g., tuberculosis, leprosy).

Question 32

What are the key differences between innate and adaptive immunity?

Answer 32

Innate immunity:
Rapid and non-specific.
Includes barriers, complement, phagocytes, NK cells, and antimicrobial peptides.
First line of defense but ineffective against many pathogens.
Adaptive immunity:
Slower to develop but highly specific.
Involves antibodies and cell-mediated responses.
Exhibits memory and cross-talks with innate immunity.

Question 33

How do different T helper cells respond to pathogens?

Answer 33

TH1:
Active against intracellular pathogens.
Activates macrophages and cytotoxic T cells.
TH2:
Active against extracellular pathogens.
Supports antibody production (especially IgE) and activates eosinophils, basophils, and mast cells.
TH17:
Active against extracellular bacteria and fungi.
Attracts neutrophils during early infection.

Question 34

How do bacterial cell wall components induce immune responses?

Answer 34

Components like LPS and peptidoglycan bind to Toll-like receptors (TLRs) on macrophages.
Binding triggers:
Inflammation.
Dendritic cell maturation.
Differentiation of T cells.
B cell activation (via TI-1 antigens).

Question 35

What are NOD-like receptors, and how do they function?

Answer 35

Nucleotide-binding oligomerization domain (NOD) receptors are intracellular sensors in the cytoplasm.
Detect bacterial components and initiate immune signaling pathways.

Question 36

How does phagocytosis aid in bacterial immunity, and what challenges can bacteria pose?

Answer 36

Phagocytosis: Effective against bacteria; phagocytes engulf and destroy pathogens.
Challenges: Some bacteria (e.g., Streptococcus pneumoniae) have protective capsules, requiring opsonization by antibodies or complement for effective clearance.

Question 37

How do vaccines protect against encapsulated bacteria like Streptococcus pneumoniae?

Answer 37

Vaccines use capsular polysaccharides to elicit an antibody response.
Examples include a polysaccharide vaccine (23 serotypes) and a conjugate vaccine for better immune memory.

Question 38

What are the key roles of antibodies in bacterial infections?

Answer 38

Opsonization: Enhance phagocyte binding via Fc receptors.
Complement activation: Triggers inflammation and pathogen lysis (especially Gram-negative bacteria).
Neutralization: Binds and neutralizes bacterial toxins (e.g., tetanus, diphtheria).
Mucosal defense: Prevents bacterial adherence to mucosal surfaces.

Question 39

How do intracellular bacteria evade immune defenses?

Answer 39

Intracellular bacteria, such as Mycobacterium tuberculosis, can survive inside phagocytes by inhibiting lysosome/phagosome fusion.
Requires a strong TH1 response with macrophage activation by cytokines like IFNγ and TNFα.

Question 40

Compare the immune responses in tuberculoid and lepromatous leprosy.

Answer 40

Tuberculoid leprosy:
Dominant TH1 response.
Few live bacteria, granuloma formation, slow progression.
Lepromatous leprosy:
Dominant TH2 response.
Disseminated infection, high bacterial load, fatal if untreated.

Question 41

What are granulomas, and why are they important in bacterial infections?

Answer 41

Granulomas are organized collections of immune cells that form around persistent infections.
Common in diseases like tuberculosis and tuberculoid leprosy.
Involves activated macrophages and cytokine production (e.g., TNFα, IFNγ).

Question 42

What is the role of the complement system in bacterial immunity?

Answer 42

Enhances phagocytosis through opsonization.
Promotes inflammation via C3a and C5a.
Forms the membrane attack complex (MAC) to lyse Gram-negative bacteria.

Question 43

Why is the TH1 response critical in intracellular bacterial infections?

Answer 43

Activates macrophages for enhanced phagocytosis and killing.
Promotes cytokine release (e.g., TNFα, IFNγ) for inflammation and immune recruitment.

Question 44

What are Toll-like receptors (TLRs), and what do they bind?

Answer 44

TLRs are pattern recognition receptors on immune cells.
Bind pathogen-associated molecular patterns (PAMPs) like LPS and nucleic acids.

Question 45

Why can Neisseria spp. infections be more severe in individuals with complement deficiencies?

Answer 45

Complement defects, particularly in terminal components, impair MAC formation, making individuals more susceptible to Neisseria infections.

Question 46

How do pathogens cause different outcomes (e.g., M. leprae)?

Answer 46

The type of immune response (TH1 vs. TH2) determines the severity and progression of the disease.