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Questions and Answers

Which cytokine is responsible for the clonal expansion of antigen-stimulated T cells?

IL-10

IL-2 (correct)

IL-6

IFN-γ

What suffix is commonly associated with inflammation?

-opathy

-itis (correct)

-algia

-emia

What is the primary function of IL-12?

Stimulates NK cell activity (correct)

Promotes wounding healing

Inhibits inflammation

Activates eosinophils

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

Numbness Signup and view all the answers

In the sequence of cell recruitment during inflammation, which type of cell is typically recruited first?

Neutrophils Signup and view all the answers

Which cytokine is produced by macrophages and induces inflammation?

IL-1 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 initial vascular change occurs during inflammation?

Vasodilation Signup and view all the answers

What role do chemokines like CXCL8 play in inflammation?

Direct migration of leukocytes Signup and view all the answers

What role does TGF-β play in the immune response?

Promotes differentiation to Treg Signup and view all the answers

Which of the following correctly represents the order of cell recruitment during an inflammatory response?

Neutrophils < Monocytes < Lymphocytes Signup and view all the answers

Which cytokine is associated with the defense against extracellular pathogens?

IL-17 Signup and view all the answers

What is the effect of Type 1 Interferons (IFN-α and IFN-β)?

Inhibit viral replication Signup and view all the answers

What process allows leukocytes to adhere tightly to the endothelial cells during inflammation?

Adhesion Signup and view all the answers

Which of the following does NOT contribute to the swelling seen during inflammation?

Vasoconstriction Signup and view all the answers

What type of response does inflammation represent?

Non-specific, localized response Signup and view all the answers

What type of molecules are recognized by Toll-Like Receptors (TLRs)?

Pathogen-Associated Molecular Patterns (PAMPs) Signup and view all the answers

Which of the following is a consequence of the engagement of Pattern Recognition Receptors (PRRs)?

Activating cells involved in innate immune responses Signup and view all the answers

Which pathway of complement activation is triggered by microbial surface structures?

Alternative Pathway Signup and view all the answers

What role do soluble mediators, such as complement proteins, play in the immune system?

They promote phagocytosis and induce inflammatory responses Signup and view all the answers

What are DAMPs responsible for in the context of immune responses?

They activate the immune system upon cell injury Signup and view all the answers

Which of the following describes the action of complement proteins after they are activated?

They initiate an enzyme cascade leading to multiple responses Signup and view all the answers

What initiates the classical pathway of complement activation?

Antibody-antigen complexes Signup and view all the answers

Which characteristic of TLRs enhances their ability to detect pathogens?

They recognize invariant PAMPs from a variety of pathogens. Signup and view all the answers

What initiates the lectin pathway of the complement system?

Mannose residues on pathogen glycoproteins binding to host lectins Signup and view all the answers

Which complement component is primarily involved in promoting phagocytosis?

C3b Signup and view all the answers

What is the main role of C5a in the complement system?

Chemotaxis of leukocytes Signup and view all the answers

Which of the following describes the function of cytokines?

Soluble proteins that may act in an autocrine, paracrine, or endocrine manner Signup and view all the answers

What is a characteristic of cytokines that exhibit pleiotropy?

They can have multiple effects on various cell types Signup and view all the answers

Which cytokine is known for its anti-inflammatory properties?

IL-10 Signup and view all the answers

What can the synergy in cytokine function lead to?

Greater effect than the sum of individual cytokines Signup and view all the answers

What is the role of C5b in the complement system?

Initiation of the membrane attack complex formation Signup and view all the answers

What is the primary difference between innate receptors and adaptive receptors?

Innate receptors recognize a broad group of pathogens whereas adaptive receptors recognize very specific pathogens. Signup and view all the answers

What role do Pattern Recognition Receptors (PRR) play in the immune system?

PRR are capable of recognizing Pathogen Associated Molecular Patterns (PAMPs). Signup and view all the answers

Which of the following statements about innate immunity is accurate?

Innate immune responses are triggered by a limited number of receptors encoded in the genome. Signup and view all the answers

What is one major characteristic of the adaptive immune system compared to the innate immune system?

The adaptive immune response takes days to weeks to develop. Signup and view all the answers

Where can Pattern Recognition Receptors (PRR) be located?

On cell surfaces, endosomal membranes, and in the cytosol. Signup and view all the answers

Which type of immunity is characterized by a broad recognition of pathogens?

Innate immunity, using limited receptors. Signup and view all the answers

Which of the following correctly describes the interaction between PRR and PAMPs?

PRR can interact with a wide range of PAMPs derived from various pathogens. Signup and view all the answers

How does the innate immune system primarily trigger its response?

By recognizing broad groups of molecular structures. Signup and view all the answers

What is the primary function of CCL2 and CCL7 in monocyte recruitment?

To bind to the CCR2 chemokine receptor Signup and view all the answers

What is NOT a prominent systemic manifestation of inflammation?

Localized swelling Signup and view all the answers

Which of the following is a significant change observed during the acute phase response?

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

Which cytokines are referred to as the 'master' cytokines involved in inflammation?

IL-1 and TNF Signup and view all the answers

What can result from local injury during inflammation?

Systemic inflammatory manifestations Signup and view all the answers

What effect do chemical mediators of inflammation primarily have?

Modulate vasodilation and vascular permeability Signup and view all the answers

Which of the following conditions is synonymous with septic shock?

Systemic inflammatory response Signup and view all the answers

Which of the following is likely to occur later than neutrophil recruitment?

Monocyte recruitment Signup and view all the answers

Study Notes

Innate Immunity

Innate immunity is a rapid, non-specific defense mechanism
Recognizes broad groups of pathogens
Uses a limited set of receptors encoded in the genome
Quickly triggers an immediate response (days) to pathogens
Recognizes pathogen-associated molecular patterns (PAMPs)

Lesson Plan

Innate immune cell recognition of pathogen (PAMPs)
Role of complement
Role of cytokines in immunity
Inflammatory response and innate cell recruitment

Innate Cell Recognition

Innate and adaptive immune systems use different strategies for pathogen recognition
Innate receptors recognize broad groups of pathogens
Adaptive receptors recognize very specific pathogens
Innate receptors are limited in number and encoded in the genome
Adaptive receptors are numerous, generated by gene rearrangements
Innate receptors interact with a range of molecular structures
Adaptive receptors discriminate between closely related structures
Innate response is immediate
Adaptive response is slower (days-weeks)

Pathogen Associated Molecular Patterns

Pattern Recognition Receptors (PRRs) are located on innate cells
PRRs recognize Pathogen Associated Molecular Patterns (PAMPs)
PRRs may be located on cell surface, endosomal membranes, and/or cytosol
Toll-Like Receptors (TLRs) are a type of PRR

TLRs: Location

Diacyl lipopeptides trigger TLR-2 and TLR-6
Triacyl lipopeptides trigger TLR-2 and TLR-1
Flagellin triggers TLR-5
dsRNA triggers TLR-3
ssRNA triggers TLR-7 and TLR-8
CpG DNA triggers TLR-9
Pathogens and associated PAMPs bind to TLRs, triggering a downstream immune response

TLRs: Specificity

TLR1/TLR2 heterodimer recognizes lipopolysaccharides (LPS), lipoproteins, etc
TLR2/TLR6 heterodimer recognizes lipoproteins (diacyl/triacyl)
TLR3 is triggered by double-stranded RNA (viruses)
TLR4 (plus MD-2 and CD14) recognizes LPS (gram-negative bacteria)
TLR5 recognizes flagellin (bacteria)
TLR7 and TLR8 recognize single-stranded RNA (viruses)
TLR9 recognizes DNA with unmethylated CpG (bacteria, herpesviruses)
TLR10 has an unknown ligand

PRRs: Consequences

Detection of PAMPs by PRRs activates innate immune responses
Aids phagocytosis
Activates innate cells
Promotes inflammatory mediators
Direct attack of microorganisms by soluble PRR molecules
Enhanced phagocytosis of PRR-bound PAMPs
Proteolytic cascade leading to microorganism lysis
Phagocytosis of PAMP and associated microorganism
Activation of immune cells encountering PAMP
Release of inflammatory mediators to amplify response

DAMPs

Danger Associated Molecular Patterns (DAMPs) are host proteins
Released during cell injury
Activate the immune system
Necrosis—uncontrolled cell death
Apoptosis—regulated cell death
PAMPs can lead to an inflammatory response
Soluble PRRs
Cell-associated PRRs
Macrophages
Immune system remains quiescent

Soluble Mediators: Complement

Complement is a collection of soluble proteins
Promotes phagocytosis through opsonization
Induces inflammatory responses
Directly kills pathogens
Proteins are proteases activated by proteolytic cleavage
Activation of one component triggers an enzyme cascade

Complement: Cascade of Activation

Classical pathway: initiated by antigen-antibody complexes activating C1
Lectin pathway: triggered by microbial cell wall components activating MBL
Alternative pathway: initiated by microbial surfaces activating factor D

Overview of Complement

C3b is deposited on the microbe
C3a triggers inflammation
C3b promotes opsonization and phagocytosis
C5a triggers inflammation
MAC leads to lysis of the microbe

Activation of Complement

Classical pathway: triggered by antigen-antibody complexes
Alternative pathway: triggered by microbial surface structures
Lectin pathway: triggered by mannose residues on pathogen glycoproteins

Complement: Inflammation

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

Complement: Opsonisation

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

Complement: Membrane Attack Complex

C5b triggers the formation of the membrane attack complex (MAC)
MAC (C5b6789) lyses bacterial, virus-infected, or tumor cells
Multiple copies of C9 form a pore in the membrane

Soluble Mediators: Cytokines

Cytokines are soluble proteins produced by various cell types
Critical for both innate and adaptive immune responses
Actions: autocrine, paracrine, and endocrine
Cytokines involved in inflammatory responses
Cytokines involved in cell growth and differentiation
Cytokines involved in cell movement and recruitment

Cytokines

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

Cytokines (Macrophages/Dendritic Cells)

TNF, IL-1, induce inflammation
IL-6, induces acute phase proteins, promotes adaptive immunity
IL-12 promotes IFN-y production and Th1 polarization
IL-23 promotes survival and function of Th17 cells
Type 1 interferon (IFN-α, ß) inhibits viral replication, promotes MHC class I expression

Cytokines (Helper T Cells)

IL-2 promotes clonal expansion of antigen-stimulated T-cells, and maintains regulatory T-cells (Treg)
IFN-y promotes activation of macrophages, increased MHC class I expression
IL-4 promotes Th2 cytokine, including class switching to IgE
IL-5 activates eosinophils
IL-17 promotes neutrophil-based inflammation

Cytokines (Anti-inflammatory)

IL-10 inhibits production of pro-inflammatory cytokines by dendritic cells, produced by Treg, DC, macrophages
TGF-ß promotes differentiation to Tregs, inhibits effector T cell function, promoting wound healing, can promote Th17 in the presence of inflammatory cytokines

Inflammation

Non-specific, localized, protective tissue response to injury
Eliminates or walls off causes of injury, and promotes tissue repair
Cardinal signs: redness, heat, swelling, pain, functional impairment

Inflammation Steps

Detection of pathogens or danger (PAMPs, DAMPs) by innate cells
Vasodilation and increased vascular permeability
Recruitment of additional immune cells (neutrophils, then monocytes, lymphocytes)
Elimination of trigger
Resolution

Inflammation: Vascular Changes

Vasodilation
Increased permeability
Reduced blood velocity
Accumulation of immune cells

Recruitment of Effector Cells

Cytokines produced by macrophages cause dilation of local blood vessels
Leukocytes move to periphery of blood vessel and extravasate
Chemokines direct the movement of neutrophils along their concentration gradient

Steps in Cell Recruitment

Rolling: random contact
Adhesion: cells stop
Trans-migration: cells cross epithelium

Neutrophil Rolling

Neutrophils are frequently the first cells to get recruited
Stimulation by inflammatory cytokines (e.g., TNF, IL-1) induces E-selectin expression on endothelium
Causes weak interactions, causing rolling of neutrophils along endothelium

Neutrophil Adhesion

Chemokines induce conformation changes in integrins (e.g., LFA-1), allowing tight binding to endothelial cells
Cells cross the blood vessel walls (extravasation)
The chemokine CXCL8 (IL-8) directs neutrophils along its gradient

Monocyte Recruitment

Monocytes are typically recruited later than neutrophils
CCL2 and CCL7 bind to CCR2 chemokine receptor, recruiting monocytes

Systemic Effects of Inflammation

Systemic protective effects
Systemic pathologic effects
Local inflammation
Endothelial cells
IL-1, TNF, TNF chemokines
IL-1, IL-6
Liver, acute-phase proteins
Fever, low output, increased endothelial permeability
Bone marrow

MBBS Learning Outcomes

Recognition of the role of immune system in defense against foreign matter
Function of immune cell types
Role of immune response in prevention of diseases
Lymphatic system and its role in defense

Reading List

Immunology for medical students
Cellular and molecular immunology

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