Immunology III: Innate Immunity & Inflammation

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Questions and Answers

What is a function of C5a?

Inhibiting bronchoconstriction

Chemotactic agent for neutrophils and macrophages (correct)

Regulating immunoglobulin production

Histamine release from mast cells

What is a consequence of complement deficiencies?

Increased risk of parasitic infections

Increased risk of viral infections

Increased risk of bacterial infections (correct)

Increased risk of fungal infections

What is a specific function of C1q?

Recognizing phosphatidylserine on apoptotic cells (correct)

Recognizing phospholipids on apoptotic cells

Recognizing immunoglobulin G on bacterial surfaces

Recognizing mannose on bacterial surfaces

What is associated with deficiencies in C1q?

Systemic lupus erythematosus Signup and view all the answers

What is a characteristic of the classical pathway?

Recognizes immunoglobulin-bound antigens Signup and view all the answers

What is a potential consequence of impaired clearance of apoptotic cells?

Increased risk of autoimmune diseases Signup and view all the answers

Which Toll-like receptor detects peptidoglycans, a major component of the cell wall of gram-positive bacteria?

TLR2 Signup and view all the answers

In which compartment are Toll-like receptors found?

ECF or endosomes Signup and view all the answers

What type of pathogens do RIG-like receptors detect?

Viruses and some bacteria Signup and view all the answers

Where are C-type Lectin receptors typically found?

On the cell membrane Signup and view all the answers

What is the downstream effect of NLR activation?

Activation of NF-KB and AP-1 Signup and view all the answers

What type of pathogens do C-type Lectin receptors detect?

Carbohydrate components of many microbes Signup and view all the answers

Where are NOD-like receptors typically found?

In the cytosol Signup and view all the answers

What type of pathogens do Toll-like receptors tend to recognize?

PAMPs in the ECF or endosomes Signup and view all the answers

What is the primary function of the complement system?

To aid in phagocytosis, destruction of microorganisms, and inflammation Signup and view all the answers

What is the common outcome of all pathways of the complement cascade?

Production of a stable C3 convertase Signup and view all the answers

Which pathway of the complement system is triggered by the binding of antibodies to a pathogen?

Classical pathway Signup and view all the answers

What is the role of C3b in the complement cascade?

It is an opsonin and causes progression through the rest of the complement cascade Signup and view all the answers

What is the function of the C5 convertase?

It cleaves C5 into C5a and C5b Signup and view all the answers

What is the role of the membrane attack complex (MAC) in the complement cascade?

It generates a pore in lipid bilayer membranes Signup and view all the answers

What is the function of C1q in the classical pathway?

It is a complement protein that binds to the Fc portion of an antibody Signup and view all the answers

What is the role of properdin in the alternative pathway?

It is a circulating protein that stabilizes the C3 convertase Signup and view all the answers

What is the consequence of unregulated complement activation?

It causes cell lysis and tissue damage Signup and view all the answers

What is the role of decay-accelerating factor, factor H, and factor I in the complement cascade?

They are proteins that down-regulate or degrade complement components Signup and view all the answers

What is the primary function of resident macrophages in tissues?

To serve as a cellular sentinel Signup and view all the answers

Which cell type is responsible for detecting PAMPs in blood and lymph vessels?

Endothelial cells Signup and view all the answers

What is the primary function of IL-1, TNF-alpha, and IL-6?

To induce acute inflammation Signup and view all the answers

What is the result of IL-1, TNF-alpha, and IL-6 acting on the hypothalamus?

Fever Signup and view all the answers

What is the primary source of IL-6?

Macrophages and monocytes Signup and view all the answers

What is the effect of IL-1, TNF-alpha, and IL-6 on vascular permeability?

Increased permeability Signup and view all the answers

What is the role of CRP and mannose-binding lectin in acute inflammation?

They are acute-phase reactants Signup and view all the answers

What is the benefit of fever in acute inflammation?

It inhibits the growth of pathogens Signup and view all the answers

What is the mechanism of peripheral vasoconstriction in fever?

Blood flow is redirected to the core Signup and view all the answers

What is the characteristic of IL-1, TNF-alpha, and IL-6 in terms of their effects?

They have redundant and pleiotropic effects Signup and view all the answers

What is the primary role of pro-inflammatory cytokines in the context of fever and acute inflammation?

To elevate the hypothalamic set-point Signup and view all the answers

Which of the following is NOT a major acute phase protein?

Interferon-gamma (IFN-γ) Signup and view all the answers

What is the primary function of C-reactive protein (CRP)?

To bind to phosphorylcholine and activate the classical complement cascade Signup and view all the answers

Which of the following is responsible for sequestering iron from microbes?

Ferritin Signup and view all the answers

What is the primary function of Type 1 interferons (IFN-α and IFN-β)?

To interfere with viral replication in a wide variety of cells Signup and view all the answers

What is the primary source of Type 1 interferons (IFN-α and IFN-β)?

Macrophages, dendritic cells, and cells that have detected viruses via PRRs Signup and view all the answers

How do Type I interferons (IFN-α and IFN-β) provide protection against viral infection?

By acting in an autocrine and paracrine fashion to provide rapid, innate protection Signup and view all the answers

What is the primary role of IFN-γ in the context of the immune response?

To activate macrophages and promote cell-mediated response Signup and view all the answers

Which of the following is a characteristic of the antiviral response mediated by Type 1 interferons?

It provides a rapid, innate protection against viral infection Signup and view all the answers

What is the primary mechanism by which prostaglandin E2 (PGE2) leads to fever?

By signaling that changes the hypothalamic set-point Signup and view all the answers

Study Notes

The Complement System

Complement is a blood-borne molecular defense system that "complements" the immunity provided by antibodies
It aids in phagocytosis, destruction of microorganisms, and inflammation
Activated through a tightly-controlled enzyme-triggered cascade
Consists of three pathways: Alternative, Classical, and Lectin pathways

Alternative Pathway

Complement component 3 (C3) acts as a pattern-recognition receptor, binding to the surface of a pathogen
C3bBb complex is formed when C3b binds to the bacterial membrane, becoming a stable C3 convertase
Properdin helps stabilize the entire complex to form the stable C3 and C5 convertases

Lectin and Classical Pathways

Mannose-binding lectin (MBL) is a circulating pattern-recognition receptor that recognizes mannose residues on bacterial membranes
C1q binds to the Fc portion of an antibody that has bound to an antigen, triggering the classical pathway
Both pathways lead to the formation of C3b and C5 convertases

Complement - General Principles

All pathways lead to the production of a stable C3 convertase
C3 convertase cleaves C3 into C3b and C3a
C3b is an important opsonin and causes progression through the rest of the complement cascade
C5 convertase cleaves C5 into C5a and C5b, leading to the formation of the membrane attack complex (MAC)

Complement - Cell Lysis

MAC generates a pore in lipid bilayer membranes, causing lysis
The sequence of events involves the assembly of C5b, C6, C7, C8, and C9, leading to the formation of the pore
Complement can be damaging to cells if not tightly regulated, and there are proteins that down-regulate or degrade complement components

FAQs about Complement

C3a and C5a cause vasodilation, increased vascular permeability, smooth muscle contraction, and histamine release from mast cells
C5a is a chemotactic agent for various cells, including neutrophils and macrophages
Complement deficiencies can lead to immunodeficiency, and C1q deficiencies are associated with systemic lupus erythematosus

Pattern Recognition Receptors (PRRs)

Toll-like receptors (TLRs) recognize PAMPs in the extracellular fluid or endosomes
C-type lectin receptors detect carbohydrate components of microbes
NOD-like receptors (NLRs) detect bacterial or parasite cell wall components in the cytosol
RIG-like receptors (RLRs) detect viral RNA in the cytosol

The Sentinels

Macrophages and dendritic cells are key sentinels for pathogen invasion or tissue damage
Endothelial cells and epithelial cells also express PRRs and play a role in detecting PAMPs

Inflammatory Mediators

IL-1, TNF-alpha, and IL-6 are major pro-inflammatory cytokines
These cytokines have redundant and pleiotropic effects, including inducing fever, increasing vascular permeability, and promoting the production of acute-phase proteins
IL-6 is a key cytokine that induces the production of acute-phase proteins

Fever and Acute Inflammation

Fever is a response to the presence of PAMPs and DAMPs, and is caused by the changing of the hypothalamic set-point
Mechanisms of fever include peripheral vasoconstriction, shivering, and increased metabolic rate
Fever has benefits, including enhancing the adaptive immune response

Acute Phase Proteins

Elevated levels of inflammatory cytokines, particularly IL-6, cause the liver to increase the secretion of acute-phase proteins
Major acute-phase proteins include C-reactive protein (CRP), ferritin, hepcidin, and serum amyloid A (SAA)
These proteins play a role in sequestering iron, opsonizing pathogens, and modulating the inflammasome and TLRs

NK Cells and IFNs

Type 1 interferons (IFN-alpha and IFN-beta) are produced by macrophages, dendritic cells, and infected cells, and play a role in protecting against viral infection
Type 2 interferons (IFN-gamma) are produced by Th cells and NK cells, and play a role in activating macrophages and promoting a cell-mediated response
NK cells are activated by the presence of infected cells or damaged cells, and differentiate between these cells and normal cells through the recognition of specific ligands
NK cells kill target cells through the release of perforin and granzymes, leading to apoptosis.

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Description

This quiz covers the basics of innate immunity and inflammation, including the complement system, pattern recognition receptors, and inflammatory mediators.