Chapter 2: Innate Immunity

Inflammation {Purpose}

• Accumulations of leukocytes and proteins at infection site or tissue injury (non-infection)

• Kills microbes and eliminates damage tissues

Antiviral Defense {Methods}

Target intracellular viruses via

• NK cells: eliminate infected cells with reduced MHC I

• Type I Interferons

Type I Interferons

Infected cell release interferons (alert) to neighboring cells so they can enter antiviral state

Innate Immunity {Sites}

• Recognize PAMP that are shared by many microbes but not present in mammalian cells (self cells)

• Present at

  • Epithelia: portals of entries that are reinforced with antimicrobial molecules & lymphoid cells (B, T, & NK cells)

  • Tissues

  • Blood: complement system

Mammalian Cells {Recognize}

Self cells that have pattern-recognition receptor (PRR) that recognize

• Viral double-stranded ribonucleic acid (dsRNA)

• Microbial unmethylated oligonucleotides that are uncommon in regular cell DNA

Pathogen-Associated Molecular Patterns (PAMPs) {Examples}

• Structures that are essential for pathogen survival and effectiveness, but also get recognize by PRR such as lipopolysaccharide (LPS), and peptidoglycans

• Around 1000 patterns

Damage-Associated Molecular Patterns (DAMPs)

Released by damaged mammalian cells or tissue such as infarction (tissue damaged from lacked of oxygen

Germline

PRR is encoded by inherited genetic DNA

Innate vs Adaptive Receptors

	Innate receptors	Adaptive receptors
Main receptors	PRRs	B & T cells receptors
Recognize	PAMPs / DAMPs	Specific antigens/epitopes
Genetic origin	Germline-encoded	Somatic V(D)J rearrangement
Diversity	Limited	Extremely diverse
Specificity	Recognize common molecular patterns	Highly antigen-specific
Memory	No classic antigen-specific memory	Yes
Found on	Many innate immune cells	B and T lymphocytes

Toll-Like Receptor (TLR)

A subset of PRR that is homologous to Drosophila Toll protein that protect flies against infections

NOD-Like Receptors Pyrin(NLRP-3) {Conditions, Release}

• A cytosolic receptors (reside in the inside cytoplasm) that recognize PAMP & DAMP

• Triggers cytokine interleukin-1β (IL-1β) when:

  • ATP released

  • Uric acid crystal derived from DNA/RNA

  • Change in intracellular potassium concentration

  • Endogenous substances deposited in cells (e.g. cholesterol)

Interleukin-1β (IL-1β)

A cytokine that activate caspase-1 that convert pre-IL-1β to the active version

Inflammasome

Multiprotein complex that activate inflammation response

• NLRP-3: sensor

• Adaptor protein: trigger

• Caspase-1: inactive enzyme

RIG-Like Receptor (RLR)

Sense viral RNA and produce type 1-IFN

Cytosolic DNA Sensor (CDS)

Sense microbial/viral DNA (ds-DNA) and produce type 1-IFN

Autophagy

When cell detects that its own cellular components are damaged, send to the lysosome for degradation

Intraepithelial Lymphocytes (IELs) {Receptor}

• Carry gamma-delta T-cell receptor (γδ-TCR) that recognize shared microbial components.

• T cells (several kinds) reside within the epithelial layer

• Specitivity and functionality are still unknown

Defensins & Cathelicidins

antimicrobial peptides released by endothelial cells that disrupt the microbes membranes

Opsonization

Process where foreign pathogens or dead cells are coated with opsonins to make them stand out for immune cells

Classical Pathway {Trigger Condition}

1. Triggers when Igs bind to microbial Ags and the Fc region is opened

2. C1q binds Fc region to activate C1r & C1s

3. C1s cleaves both C4 & C2

Lectin Pathway {Trigger Condition}

1. Initiates by mannose-bind lectin (MBL) attaches to mannose of microbes

2. MBL-associated serine proteases (MASP-1 & MASP-2) becomes activated

3. MASP-1 & MASP-2 performs similar job as C1s by cleaving C4 & C2

Alternate Pathway {Trigger Condition}

• Triggers when C3b (hydrolyze from C3) opsonizes the microbe (binds to factor b)

• Factor D then cleaves it into C3 convertase (C3bBb) and Ba

• Properdin stabilizes the C3 convertase