Innate Immunology

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Questions and Answers

What role do Pathogen Associated Molecular Patterns (PAMPs) play in inflammation?

They are released by necrotic cells.

They facilitate vasodilation.

They prevent the recruitment of immune cells.

They activate inflammatory cytokines. (correct)

Which statement best describes the function of Toll-Like Receptors (TLRs) in the immune response?

TLRs promote vasodilation in blood vessels.

TLRs are involved in monocyte recruitment directly.

TLRs assist in the recognition of PAMPs. (correct)

TLRs inhibit the secretion of inflammatory mediators.

What is the primary function of cytokines in the inflammatory response?

To eliminate pathogens directly through lysis.

To increase vascular permeability and recruit immune cells. (correct)

To block the vasodilation process.

To cause necrosis in surrounding tissues.

How does the complement system contribute to inflammation?

By enhancing the ability of antibodies and phagocytic cells to clear pathogens. Signup and view all the answers

Which cells are typically recruited first during the inflammatory response?

Neutrophils. Signup and view all the answers

Which statement about Pathogen Associated Molecular Patterns (PAMPs) is correct?

PAMPs trigger immediate responses from the innate immune system. Signup and view all the answers

What is the primary role of Pattern Recognition Receptors (PRRs) like Toll-Like Receptors (TLRs)?

To recognize Pathogen Associated Molecular Patterns (PAMPs). Signup and view all the answers

Which consequence is associated with the detection of DAMPs?

Activation of the immune system. Signup and view all the answers

What is NOT a function of the complement system?

Inducing apoptosis in infected cells. Signup and view all the answers

Which feature distinguishes innate receptors from adaptive receptors?

Innate receptors can respond to a wide range of pathogens. Signup and view all the answers

Which statement is true regarding the specificity of Toll-Like Receptors (TLRs)?

TLRs interact with a range of molecular structures. Signup and view all the answers

How do cytokines function in the immune response?

By modulating the behavior of immune cells. Signup and view all the answers

What triggers the classical pathway of complement activation?

Presence of an antibody-antigen complex Signup and view all the answers

Which of the following components is activated in the complement system to enhance opsonization?

C3b Signup and view all the answers

Which cytokine is classified as anti-inflammatory?

IL-10 Signup and view all the answers

What is the role of C5a in the immune response?

Induces mast cell degranulation Signup and view all the answers

Which pathway of complement activation is triggered by microbial structures like LPS?

Alternative pathway Signup and view all the answers

What mediates the directed movement of leukocytes towards the site of infection?

C5a Signup and view all the answers

What common feature is shared by the complement pathways upon activation?

Activation of C3 convertase Signup and view all the answers

Which type of receptors are frequently involved in recognizing PAMPs in the immune response?

Toll-like receptors Signup and view all the answers

Which cytokines are primarily associated with cell growth and differentiation?

Colony-stimulating factors Signup and view all the answers

What is the final structure formed by the complement system that can lead to cell lysis?

Membrane attack complex (MAC) Signup and view all the answers

Study Notes

Innate Cell Recognition of Pathogen

Innate and adaptive immune systems differ in pathogen recognition strategies.
Innate receptors are limited in number, encoded in the genome, recognize broad groups of pathogens and trigger immediate responses.
Adaptive receptors are numerous due to gene rearrangements, are clonally distributed, recognize specific pathogens and trigger slower responses.

Pathogen Associated Molecular Patterns (PAMPs)

Pattern recognition receptors (PRRs) are receptors on innate cells that recognize PAMPs.
PRRs can be found on the cell surface, endosomal membranes and cytosol.
Toll-like receptors (TLRs) are a key type of PRR.

TLRs: Location

TLRs have diverse locations within cells, allowing for broad recognition of pathogens.
TLRs can be found on plasma membranes, endosomes and cytosol.

TLRs: Specificity

TLRs are specialized to recognize specific PAMPs.
TLR4 recognizes lipopolysaccharide (LPS) from Gram-negative bacteria.
TLR3 recognizes double-stranded RNA from viruses.
TLR5 recognizes flagellin from bacteria.
TLR9 recognizes unmethylated CpG DNA from bacteria.

PRRs : Consequences

When PRRs detect PAMPs, they initiate innate immune responses.
These responses include:
- Phagocytosis
- Activation of innate cells
- Promotion of inflammatory mediators

DAMPs

Danger Associated Molecular Patterns (DAMPs) are host proteins that are released during cell injury.
They also activate the immune system.

Soluble Mediators: Complement

Complement is a collection of soluble proteins that activate the immune system upon activation.
Complement can:
- Promote phagocytosis through opsonization.
- Induce inflammatory responses.
- Directly kill pathogens.

Complement: Cascade of Activation

Activation of complement components triggers an enzyme cascade involving a series of proteolytic cleavages.

Overview of Complement

Complement activation occurs through three pathways:
- Classical Pathway: Triggered by antigen-antibody complexes.
- Alternative Pathway: Triggered by microbial surface structures, such as lipopolysaccharide (LPS).
- Lectin Pathway: Triggered by mannose residues on pathogen glycoprotiens binding to host lectins.

Complement: Inflammation

C3a and C5a are anaphylatoxins that cause mast cell degranulation and promote vascular permeability.
C5a is a chemotactic factor, attracting leukocytes.

Complement: Opsonisation

C3b binds to the outer surface of microbes.
This is recognized by complement receptor 1 (CR1) on phagocytes, promoting phagocytosis and destruction of pathogens.

Complement: Membrane Attack Complex (MAC)

C5b triggers the formation of the MAC (C5b6789).
MAC causes lysis of bacterial, virus infected and tumor cells.
Contains multiple copies of C9.

Soluble Mediators: Cytokines

Cytokines are soluble proteins produced by various cells.
Critical for innate and adaptive immune responses.
Expression of cytokines may be altered in many immune, inflammatory, and infectious diseases.
Action of cytokines can be autocrine, paracrine, or endocrine.

Cytokine Types

Cytokines play diverse roles:
- Proinflammatory: IL-1, IL-6, TNF-α, IFNγ
- Anti-inflammatory: TGF-β, IL-10
- Cell growth and differentiation: Colony-stimulating factors (CSFs) and stem cell factor
- Involved in cell movement and recruitment or chemotaxis: chemokines (e.g. CXCL8/IL-8)
- Promote wound healing (if chronic, can promote fibrosis. But in presence of inflammatory cytokine, can promote Th17.)

Inflammation I

Inflammation is a non-specific localized protective response to injury, like infection, trauma, or heat.
It aims to eliminate or wall off the cause of injury and necrotic cells, promoting tissue repair.
Often denoted by the suffix “-itis.”

Cardinal Signs of Inflammation

Five cardinal signs of inflammation include:
- Redness
- Heat
- Swelling
- Pain
- Functional Impairment

Inflammation Steps

Detection of pathogens or danger (PAMPs, DAMPs) by innate cells leads to 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 causes increased blood flow leading to warmth and redness.
Increased permeability allows protein-rich fluid leakage, leading to swelling.
Reduced blood velocity occurs.
Accumulation of immune cells occurs.

Recruitment of Effector Cells

Recruitment of effector cells to the site of infection is crucial.
Recruitment is a time-dependent process: Neutrophils < Monocytes < Lymphocytes

Neutrophil Recruitment: Rolling

Neutrophils often arrive first.
Activation by inflammatory cytokines induces E-selectin expression on endothelium.
Weak interactions between E-selectin and neutrophil ligands cause rolling along the vessel wall.

Neutrophil Recruitment: Adhesion

Chemokines (e.g. CXCL8/IL-8) change integrin conformation, allowing for tight adherence to endothelial cells.
Chemokines also attract neutrophils to the sites of infection.
Cells cross the blood vessel walls (extravasation).

Neutrophil Recruitment in Action

The process of neutrophil rolling, adhesion, and extravasation is a coordinated action that is crucial for directing neutrophils to areas of inflammation.

Monocyte Recruitment

Monocytes are typically recruited several hours after neutrophils.
Chemokines CCL2 and CCL7 bind to CCR2, recruiting monocytes.

Inflammation II

Ideally inflammation is localized.
In some cases local injury can lead to systemic manifestations as inflammatory mediators are released into the blood.

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Description

Explore the mechanisms of innate cell recognition of pathogens, focusing on the role of pattern recognition receptors (PRRs) and Toll-like receptors (TLRs). This quiz will cover the differences between innate and adaptive immune responses, as well as the specificity and location of TLRs. Test your knowledge on how these receptors play a crucial role in immune defense.