Innate Immunity

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Questions and Answers

What role do Toll-Like Receptors (TLRs) play in the immune system?

They initiate innate immune responses. (correct)

They solely recognize DAMPs.

They directly kill pathogens.

They promote the generation of antibodies.

Which of the following statements about the Complement system is true?

All complement proteins are membrane-bound.

Complement activation can trigger a cascade of enzymatic reactions. (correct)

Complement proteins are only involved in phagocytosis.

Complement solely relies on antibody activation.

What triggers the Classical Pathway of complement activation?

Microbial surface structures.

Pro-inflammatory cytokines.

Viral RNA presence.

Antibody-antigen complexes. (correct)

Which immune response is NOT a consequence of Pattern Recognition Receptors (PRRs) detecting PAMPs?

Activation of adaptive immune cells. Signup and view all the answers

What are DAMPs and how do they contribute to the immune response?

They are released during cell injury and activate the immune system. Signup and view all the answers

What is the primary function of the Alternative Pathway of complement activation?

Activated by microbial surface structures. Signup and view all the answers

Which of the following best describes opsonization in the context of the complement system?

Coating of pathogens to enhance phagocytosis. Signup and view all the answers

Which of the following best describes the cascade of activation in the complement system?

Each activated component activates multiple downstream components. Signup and view all the answers

What triggers the lectin pathway of complement activation?

Binding of lectins to mannose residues on pathogen glycoproteins Signup and view all the answers

What is the role of C3a and C5a in the immune system?

They act as powerful anaphylatoxins causing mast cell degranulation. Signup and view all the answers

What effect does C3b have during the immune response?

Promotes phagocytosis by being recognized by complement receptor 1. Signup and view all the answers

What is the primary function of the membrane attack complex (MAC)?

To promote the lysis of bacterial and virus-infected cells. Signup and view all the answers

Which of the following is a characteristic of cytokines?

Cytokines show redundancy where multiple cytokines can produce similar effects. Signup and view all the answers

What type of interactions can cytokines have within the immune system?

They may exhibit synergy, redundancy, and antagonism. Signup and view all the answers

Which cytokines are classified as pro-inflammatory?

IL-1, IL-6, TNF-α, IFNγ Signup and view all the answers

What does the term 'pleiotropic' refer to in relation to cytokines?

Having multiple effects on different cell types. Signup and view all the answers

What role does IL-6 play in the immune response?

Promotes acute phase proteins from the liver Signup and view all the answers

Which cytokine is mainly responsible for promoting Th1 polarization of helper T cells?

IL-12 Signup and view all the answers

What function does TGF-β serve in the immune system?

Inhibits effector T cell function and promotes Treg differentiation Signup and view all the answers

Which cytokine is primarily produced in response to viral infection?

Type 1 Interferon (IFN-α, β) Signup and view all the answers

What is the main function of IL-2 in the immune response?

Facilitates clonal expansion of antigen-stimulated T cells Signup and view all the answers

Which cytokine inhibits the production of pro-inflammatory cytokines by dendritic cells?

IL-10 Signup and view all the answers

What does IL-4 promote in the immune system?

Class switching to IgE Signup and view all the answers

What is a primary characteristic of inflammation?

It is a non-specific response to protect against various types of harm. Signup and view all the answers

Which of the following is NOT a cardinal sign of inflammation?

Fever Signup and view all the answers

What is the primary role of vasodilation during inflammation?

To increase blood flow to the affected area Signup and view all the answers

Which type of immune cell is typically recruited first during the inflammatory response?

Neutrophils Signup and view all the answers

The process of leukocyte exiting the blood vessels is known as:

Diapedesis Signup and view all the answers

In the inflammatory response, what is an effect of increased vascular permeability?

Swelling due to fluid accumulation Signup and view all the answers

What signal induces the expression of E-selectin on endothelial cells during inflammation?

TNFα Signup and view all the answers

Which chemokine is primarily responsible for directing neutrophil migration during inflammation?

CXCL8 Signup and view all the answers

Recruitment of which immune cell type occurs last in the series during the inflammatory response?

Lymphocytes Signup and view all the answers

What is the primary role of CCL2 and CCL7 in inflammation?

They bind to CCR2 to recruit monocytes. Signup and view all the answers

Which of the following is NOT a prominent systemic manifestation of inflammation?

Vasodilation Signup and view all the answers

What is a major change observed during the acute phase response in inflammation?

Increase of acute phase proteins in the serum Signup and view all the answers

Which cytokines are considered the 'master cytokines' influencing inflammation?

IL-1 and TNF Signup and view all the answers

Which condition is termed the systemic inflammatory response?

Sepsis and septic shock Signup and view all the answers

What is the impact of chemical mediators on vasodilation?

They increase blood flow to injured tissues. Signup and view all the answers

How does local injury affect the systemic response?

It can lead to pronounced systemic manifestations. Signup and view all the answers

What common treatment targets the effects of inflammation?

Anti-inflammatory drugs Signup and view all the answers

Study Notes

Toll-Like Receptors (TLRs)

Detect Pathogen-Associated Molecular Patterns (PAMPs)
Found on the surface of cells of the innate immune system
Crucial for detecting microbial infections

Pattern Recognition Receptors (PRRs)

Recognize PAMPs and Damage-Associated Molecular Patterns (DAMPs)
Activate innate immune responses:
- Aid phagocytosis
- Activate innate cells
- Promote inflammatory mediators

Danger Associated Molecular Patterns (DAMPs)

Host proteins released during cell injury
Activate the immune system

Complement

A collection of soluble proteins that activate upon injury.
Aids the immune system by:
- Promoting phagocytosis through opsonisation.
- Induce inflammatory responses.
- Directly kill pathogens.

Activation of Complement

Activation of one component triggers an enzyme cascade.

Overview of Complement Pathways

Classical Pathway: Triggered by the presence of an antibody-antigen complex
Alternative Pathway: Triggered by microbial surface structures e.g. LPS
Lectin Pathway: Triggered by mannose residues on pathogen glycoproteins binding to host lectins
Common Feature: Activation of C3 convertase which converts C3 into C3a and C3b

Complement: Inflammation

C3a and C5a are powerful anaphylatoxins
Cause mast cell degranulation
Promote vasodilation and increase vascular permeability
C5a is chemotactic factor

Complement: Opsonisation

C3b attaches to the outside of the microbe
Is recognised by complement receptor 1 (CR1) on phagocytes
Promotes phagocytosis and destruction of the pathogen

Complement: Membrane Attack Complex (MAC)

C5b triggers the formation of MAC (C5b6789)
Causes lysis of bacterial, virus-infected, or tumour cells
Contains multiple copies of C9

Soluble Mediators: Cytokines

Soluble proteins produced by a variety of cell types.
Critical for innate and adaptive immune responses.
Their expression can be perturbed in immune, inflammatory, and infectious disease states.
Actions can be autocrine, paracrine, or endocrine.
Include proinflammatory (e.g., IL-1, IL-6, TNF-α, IFNγ), anti-inflammatory (e.g., TGF-β, IL-10), and involved in cell growth and differentiation (e.g., colony-stimulating factors (CSFs) and stem cell factor).

Cytokine Properties

Pleiotropic: Having more than one effect
Redundancy: Several cytokines can have the same effect
Synergy: The effect of two cytokines may be greater than the sum of each effect
Antagonism: One cytokine may inhibit the response to another cytokine
Cytokine Networks: Cytokines enhance or suppress the production of others generating complex cytokine networks.

Cytokine Examples

Produced by macrophages/dendritic cells upon stimulation:
- TNF, IL-1: Induce inflammation, by acting on the endothelial cell
- IL-6: Induced acute phase proteins from the liver, promotes adaptive immune responses
- IL-12: Promotes IFN-γ production and Th1 polarisation of helper T cells. Stimulates NK cell activity
- IL-23 Promotes survival and function of Th17 cells
Produced in response to virus:
- Type 1 Interferon (IFN-α, β) Inhibits viral replication, promotes MHC class I expression and cytotoxic T cells.
Produced by helper T cells:
- IL-2: Clonal expansion of antigen-stimulated T cells, maintenance of regulatory T cells (Treg)
- IFN-γ: Product of Th1 cells (and NK cells), promotes activation of macrophage to be better killers of intracellular bacteria, increased MHC class I expression
- IL-4: Th2 cytokine, includes class switching to IgE
- IL-5: Activates eosinophils
- IL-17: Th17 cytokine, promotes neutrophil-based inflammation in defense against extracellular pathogens

Anti-inflammatory Cytokines

IL-10 inhibits the production of pro-inflammatory cytokine by dendritic cells; produced by Treg, DC, and macrophages (later response)
TGF-β: Promotes differentiation to Treg, inhibitor effector T cell function; produced by Treg and other cells. Can promote wound healing (if chronic fibrosis). But, in the presence of inflammatory cytokines, can promote Th17.

Inflammation

Non-specific, localized, protective tissue response to injury (e.g., infection, trauma, heat).
Intended to eliminate or wall off the cause of injury, necrotic cells, and promote tissue repair.
Denotes by suffix “-itis”

Cardinal Signs of Inflammation

Redness
Heat
Swelling
Pain
Functional Impairment

Steps in Inflammation

Detection of pathogens or danger: (PAMPs, DAMPs) by innate cells results in the release of mediators that cause vascular and cellular responses
Vasodilation and increased vascular permeability:
Recruitment of additional immune cells: (neutrophils, then monocytes, then lymphocytes)
Elimination of trigger:
Resolution:

Inflammation: Vascular Changes

Vasodilation: Increases blood flow (red, warm)
Increased permeability: Leads to exudation of protein-rich fluid (swelling)
Reduced blood velocity:
Accumulation of immune cells:

Recruitment of Effector Cells

Recruitment of effector cells to the site of infection is an important step in controlling infection.

Steps in Cell Recruitment

Time: Neutrophils < Monocytes < Lymphocytes

Neutrophil Recruitment: Rolling

Neutrophils are often the first cell recruited.
Activation by inflammatory cytokines (e.g., TNFα, IL-1) induces expression of E-selectin on the endothelium.
Weak interactions with carbohydrate ligands on the neutrophils, slows movement, causing rolling.

Neutrophil Recruitment: Adhesion

Chemokines induce conformation changes in integrins (e.g., LFA-1), allowing the leukocyte to adhere tightly to the endothelial cells via interactions with their ligands (e.g., ICAM-1, also upregulated by inflammatory cytokines like TNF).
Cells cross the blood vessel walls (extravasation).
The chemokine CXCL8 (aka IL-8) directs the migration of neutrophils along its concentration gradient.

Monocyte Recruitment

Monocytes are typically recruited (hours) later than neutrophils.
CCL2 and CCL7 both bind to CCR2 chemokine receptor and recruit monocytes.

Inflammation Systemic Effects

Ideally, the inflammatory response remains confined to a localised area.
Local injury can result in prominent systemic manifestations as inflammatory mediators are released into the circulation.
Acute phase response: A group of physiologic processes occurring soon after the onset of inflammation. The most prominent change is a dramatic increase of acute phase proteins in the serum.
Alterations in white blood cell count: (leukocytosis or leukopenia)
Fever:
Sepsis and septic shock: (systemic inflammatory response syndrome) Represents the severe systemic manifestations of inflammation.

Inflammation: Chemical Mediators

Chemical mediators of inflammation impact:
- Vasodilation
- Vascular permeability
- Chemotaxis
- Fever
- Pain
- Tissue Damage
Often the target of anti-inflammatory drugs.

Systemic Effects of Inflammation

IL-1 and TNF are considered the “master cytokines”

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Description

Test your understanding of Toll-Like Receptors (TLRs) and the Complement System within the innate immune response. This quiz covers the roles of Pattern Recognition Receptors (PRRs), Danger-Associated Molecular Patterns (DAMPs), and the activation pathways of complement proteins. Explore the intricate mechanisms that protect the body against microbial infections.