Lecture 5 Objective Questions

What are the main external defenses of innate immunity?

Intact skin and mucosal surfaces

How does skin protect against infection?

Acts as a physical barrier with constant turnover

What bodily functions help remove microbes externally?

Cilia movement and peristalsis

What secretions contribute to innate defense?

Sweat, sebum, stomach acid, mucus, tears, saliva

How does acidity help innate immunity?

Low pH inhibits microbial growth

What is lysozyme?

An enzyme that cleaves bacterial cell wall components

Where is lysozyme found?

Tears, saliva, and other secretions

What is normal flora?

Beneficial microbes that compete with pathogens

What are internal defenses of innate immunity?

Complement, acute-phase response, cellular response

What is the cellular response of innate immunity?

Immune cell recognition and destruction of microbes

What processes are involved in innate cellular defense?

Phagocytosis, lytic enzymes, ROS, cytotoxicity, inflammation

What characterizes innate immune proteins?

Broad specificity, not antigen-specific

What do innate immune proteins recognize?

Molecular patterns unique to pathogens

What induces the acute-phase response?

Cytokines such as IL-6 acting on the liver

What are acute-phase proteins?

Proteins produced by the liver during infection or inflammation

What is C-reactive protein (CRP)?

An acute-phase protein that binds bacterial components

What does CRP bind on bacteria?

Lipopolysaccharides (LPS)

Functions of CRP?

Opsonization and complement activation

How much can CRP increase during infection?

100–1000 fold

Why is CRP clinically useful?

Indicator of acute inflammation and treatment response

What other conditions raise CRP?

Autoimmune disease, transplant rejection, heart attack

What is serum amyloid A (SAA)?

Acute-phase protein elevated especially in bacterial infections

Functions of SAA?

Activates monocytes/macrophages and cytokine production

What is alpha-1 antitrypsin (AAT)?

Acute-phase protein that inhibits proteases

Function of AAT?

Limits host tissue damage and regulates inflammation

What is haptoglobin?

Acute-phase protein that binds free hemoglobin

Why is haptoglobin important?

Prevents oxidative damage

What is fibrinogen?

Acute-phase protein involved in blood clotting

How does fibrinogen aid immunity?

Promotes healing and limits microbial spread

What are PAMPs?

Pathogen-associated molecular patterns

Why are PAMPs effective targets?

Conserved structures unique to pathogens

Examples of PAMPs?

LPS, flagellin

What are PRRs?

Pattern-recognition receptors

What PRR binds LPS?

Toll-like receptor 4 (TLR4)

What PRR binds flagellin?

Toll-like receptor 5 (TLR5)

What happens when PRRs bind PAMPs?

Innate cell activation

Effects of PRR-PAMP binding?

Inflammation, phagocytosis, adaptive immunity activation

How many TLRs exist in humans?

About 10

Where are TLRs located?

Cell surface and endosomes

What do C-type lectin receptors recognize?

Carbohydrates on fungal cell walls

What do RIG-I-like receptors detect?

Viral nucleic acids in the cytoplasm

What do NOD-like receptors detect?

Bacterial components in the cytoplasm

Which innate cells perform phagocytosis?

Neutrophils, macrophages, dendritic cells

What draws innate cells to infection sites?

Chemotaxis

How do innate cells bind microbes?

PRRs and receptors for opsonins

What is the first step of phagocytosis?

Binding of the microbe

How is a phagosome formed?

Membrane invagination and pseudopodia fusion

What happens after phagosome formation?

Fusion with lysosomes

What is a phagolysosome?

Phagosome fused with lysosome

What environment exists inside phagolysosomes?

Acidic and proteolytic

What are primary granules?

Granules with proteolytic enzymes and antimicrobial proteins

What are secondary granules?

Granules containing ROS-producing components

What are reactive oxygen species (ROS)?

Toxic oxygen-derived molecules that kill microbes

When are ROS produced?

During phagocytosis (oxidative burst)

What enzyme produces ROS?

NADPH oxidase

Where is NADPH oxidase located?

Phagolysosome membrane

What is the first ROS produced?

Superoxide anion (O2-)

What ROS are derived from superoxide?

Hydrogen peroxide, hydroxyl radical, hypochlorite

How do ROS kill microbes?

Damage proteins, membranes, and DNA

Why does acidity increase during phagocytosis?

H+ and K+ influx activates proteases

What are defensins?

Antimicrobial peptides that disrupt cell walls

What happens to antigen fragments after degradation?

Some are presented to T cells

What cells provide early defense against virus-infected cells?

Natural killer (NK) cells

What do NK cells target?

Virus-infected cells and altered-self cells

How do NK cells recognize targets?

By surface protein expression, not antigens

Which cytokines activate NK cells?

Type I interferons and IL-12

What cytokines do NK cells produce?

IFN-γ and TNF-α

What receptors regulate NK cell activity?

Inhibitory and activating receptors

What determines NK cell killing?

Balance between inhibitory and activating signals

What do inhibitory NK receptors bind?

MHC class I molecules

Why do normal cells avoid NK killing?

They express sufficient MHC class I

What happens when MHC class I is reduced?

Inhibitory signals decrease

What do activating NK receptors bind?

Stress-induced proteins on target cells

Why do virus-infected cells get killed by NK cells?

Viral infection reduces MHC class I expression

What molecules do NK cells use to kill targets?

Perforin and granzymes

Function of perforin?

Forms pores in target cell membranes

Function of granzymes?

Induce apoptosis and DNA fragmentation

What is ADCC?

Antibody-dependent cell-mediated cytotoxicity

What immune components are required for ADCC?

Antibodies and innate immune cells

Which cells can perform ADCC?

NK cells, macrophages, neutrophils, eosinophils

What part of the antibody binds the target cell?

Fab region

What part of the antibody binds immune cells?

Fc region

How do immune cells bind antibodies in ADCC?

Via Fc receptors

What is the outcome of ADCC?

Target cell apoptosis and destruction

What are common targets of ADCC?

Virus-infected cells and parasites

Why is ADCC important for parasites?

Parasites are too large to be phagocytosed