Innate Immunity and TLRs Overview

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Questions and Answers

What is the role of the receptor for bacterial endotoxin (LPS) in macrophages?

It transduces signals via an attached Toll-like receptor. (correct)

It primarily activates NK cells.

It inhibits the production of transcription factors.

It promotes the secretion of soluble factors.

Which cytokine is most important for activating macrophages?

IFNγ (correct)

TNFα

IL-10

IL-12

What common function do activating receptors on macrophages share?

They inhibit transcription factor production.

They induce the production of transcription factors. (correct)

They stimulate the release of cytokines only.

They only affect NK cell activity.

How do NK cells respond to IL-12 produced by macrophages?

By secreting IFNγ. Signup and view all the answers

What is a function of the normal flora in the oral cavity and skin?

They compete with pathogens for resources. Signup and view all the answers

Which of the following is NOT considered a soluble factor in the immune response?

Macrophages Signup and view all the answers

Which component is a key antimicrobial in the innate immune system?

Lysozyme Signup and view all the answers

What is the main benefit of the reticuloendothelial system?

It filters blood to eliminate pathogens. Signup and view all the answers

What role do transcription factors play in the activation of macrophages?

They facilitate protein synthesis necessary for immune response. Signup and view all the answers

What is the primary role of C-Reactive Protein (CRP) in innate immunity?

To activate the classical complement pathway and opsonize microbes Signup and view all the answers

Where is C-Reactive Protein (CRP) produced in the body?

In the liver Signup and view all the answers

Which condition may interfere with the normal response of CRP production?

Severe hepatocellular impairment Signup and view all the answers

What structure does CRP form when five identical subunits associate?

Pentamer Signup and view all the answers

What is the effect of CRP binding to phosphocholine?

Activation of the classical complement pathway Signup and view all the answers

Which function is NOT associated with defensins?

Production of antibodies Signup and view all the answers

What distinguishes defensins from other antimicrobial proteins?

They have a small molecular weight and cationic charge Signup and view all the answers

In which part of the body would defensins primarily be found?

Primary granules of neutrophils Signup and view all the answers

What is the primary physiological trigger for an increase in CRP levels?

Acute inflammatory stimulus Signup and view all the answers

Which of these factors does NOT lead to the protective role of defensins?

Stimulation of adaptive immunity Signup and view all the answers

What is the primary function of natural killer (NK) cells in innate immunity?

To recognize and kill infected or tumor cells Signup and view all the answers

Which component is NOT considered a physical barrier in innate immunity?

Cytokines Signup and view all the answers

Which cytokine is specifically associated with fever production?

Tumor necrosis factor (TNF) Signup and view all the answers

What is the role of Toll-Like Receptors (TLRs) in innate immunity?

To recognize components of microbial cells Signup and view all the answers

Which cells are primarily responsible for the production of pro-inflammatory cytokines?

Macrophages Signup and view all the answers

What defines the primary response of innate immunity?

Rapid and non-specific against a wide range of microbes Signup and view all the answers

Which cells are primarily responsible for synthesizing complement proteins?

Hepatocytes Signup and view all the answers

Which of the following cytokines is known for its antiviral activity?

Interferon-alpha (IFN-α) Signup and view all the answers

What is the main mechanism through which complement mediates the direct killing of bacteria?

Formation of the membrane attack complex (MAC) Signup and view all the answers

Which of these is a plasma protein involved in innate immunity?

C-reactive protein Signup and view all the answers

Which of the following is NOT a function of complement?

Activation of the adaptive immune response Signup and view all the answers

How do phagocytes contribute to innate immunity?

By engulfing and digesting microbes Signup and view all the answers

In the classical pathway of complement activation, which component directly binds to antibodies?

C1 Signup and view all the answers

Which statement best describes the innate immunity's role in stimulating acquired immunity?

Innate immunity primes the immune system for faster response to subsequent infections. Signup and view all the answers

What role does C3b play in the immune response against bacteria?

It mediates opsonization for phagocytosis Signup and view all the answers

Which activator is part of the alternative pathway for complement activation?

Lipopolysaccharides (LPS) Signup and view all the answers

Which component stabilizes the C3 convertase in the alternative pathway?

Properdin Signup and view all the answers

What is a key requirement for the alternative pathway to be activated?

Foreign substances like LPS or bacterial cell walls Signup and view all the answers

How does C3 contribute to bacterial clearance in the bloodstream?

By binding to erythrocytes and transporting bacteria Signup and view all the answers

What occurs after C3b binds to foreign substances?

It facilitates the formation of C3 convertase Signup and view all the answers

What initiates the activation of the classical pathway?

Antigen-IgG complex Signup and view all the answers

Which of the following proteins activates C4 in the classical pathway?

C1s Signup and view all the answers

What is the main difference between the lectin pathway and the classical pathway?

The lectin pathway requires mannose-binding lectin. Signup and view all the answers

Which of the following activities is NOT associated with complement fragments?

Inhibition of neutrophil migration Signup and view all the answers

Which complement deficiency is associated with increased susceptibility to Neisseria infections?

Factor D deficiency Signup and view all the answers

What is one of the adverse effects of systemic production of complement during disease pathogenesis?

Anaphylaxis following Gram-negative sepsis Signup and view all the answers

Study Notes

Innate Immunity

Innate immunity is the natural, nonspecific defense mechanism against infections and cancer.
Components include physical barriers, phagocytes, natural killer (NK) cells, the complement system, cytokines, and other plasma proteins.
Phagocytes, such as monocytes, macrophages, and neutrophils, engulf and destroy pathogens.
NK cells kill host cells infected with intracellular microbes.
External defenses include skin, stomach acidity, mucus, cilia, microflora, lysozyme in tears, and flushing of the urinary tract.

Toll-Like Receptors (TLRs)

TLRs recognize diverse components of bacterial cells.
TLRs are important for activating macrophages.

Functions of Activated Macrophages

Macrophages are activated by signals from surface receptors.
Activated macrophages produce several proteins that mediate their function.
Activation leads to the production of transcription factors.

C-Reactive Protein (CRP)

CRP is a pentameric protein that reacts with the somatic C polysaccharide of Streptococcus pneumoniae.
It binds to phosphocholine, found in phospholipid membranes of many organisms.
Role in innate immunity includes: activating the classical complement pathway, opsonizing ligands for phagocytosis, neutralizing platelet-activating factor (PAF), and down-regulating polymorphonuclear leukocytes (neutrophils, eosinophils, basophils).

### CRP Synthesis and Regulation

Exclusively made in the liver.
Secreted in increased amounts during acute inflammation.
Levels peak after about 50 hours.
Normal response is inhibited by severe hepatocellular impairment.

Defensins

Family of cationic proteins found in neutrophils and mononuclear phagocytes.
Bactericidal, also kill fungi and viruses.
Chemotactic for monocytes, attracting the "second wave" of leukocytes.

Complement System

Direct and indirect killing of bacteria and virus-infected cells.
Lysis mediated by the membrane attack complex (MAC).
Opsonization followed by phagocytosis and intracellular killing.
Complement concentration in serum doesn't increase with immunization.

C3 in Bacterial Clearance and Killing

C3 bound to bacteria as C3b or iC3b binds to CR1 on erythrocytes, transporting bacteria through circulation.
C3 deposition on bacterial membranes facilitates MAC formation.
C3 ligates complement receptors on phagocytes, activating them for phagocytosis, respiratory burst, and bacterial killing.

Alternative Pathway

Activated by lipopolysaccharides, bacterial cell walls, yeast cell walls, aggregated IgA, and cobra venom.
Does not require antibodies or IgM for activation.

Activation Cascade of the Alternative Pathway

C3b binds to foreign substance.
C3b + Factor B forms C3bB.
Factor D cleaves Factor B, forming C3bBb.
C3bBb acts as C3 convertase, cleaving C3 into C3a and C3b.
Properdin stabilizes C3bBb, while Factor I and H inactivate free C3b.

Classic Pathway (CP)

Activated by antigen-IgG complex or pentameric IgM.
IgG4, IgA, IgE cannot activate CP as they lack C1q receptors.

Steps of CP Activation

C1q-FcIgG activates C1r and C1s.
C1s activates C4, producing C4a and C4b.
C4b activates C2, forming C4b2a (C3 convertase) and 2b.
C4b2a activates C3.
C5, C6, and C7 are activated.
C8 and C9 are activated, forming MAC.

The Lectin Pathway (LP)

Activated by mannose-binding lectin (MBL), a plasma protein similar to C1q.
MBL binds to terminal mannose on microbial glycoproteins.
Activates classical pathway proteins.
Does not require antibodies, making it part of innate immunity.

Three Functions of Complement in Host Defense

Opsonization: C3b binds to microbes, facilitating phagocytosis.
Chemotactic activity of C5a: Attracts neutrophils and monocytes to the site of infection, promoting inflammation.
Formation of membrane attack complex (MAC): Creates pores in microbial membranes, causing lysis and death.

Complement Protein Deficiencies

Defects in the alternative pathway can lead to susceptibility to Haemophilus influenzae.
Deficiencies in Factor D and Properdin increase Neisseria infections.
C5 deficiency is less severe but increases susceptibility to Neisseria gonorrheae and N. meningitidis.

Complement and Disease Pathogenesis

Systemic production of anaphylaxis, as in Gram-negative sepsis.
Immune complex deposition in tissues.
May cause tissue damage.

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Description

This quiz explores the fundamental concepts of innate immunity, including the components and functions of the immune response. It covers key elements such as phagocytes, natural killer cells, and the role of Toll-Like Receptors (TLRs) in activating the immune system. Test your knowledge on how the body defends against infections and the roles of various proteins like C-Reactive Protein.