Innate Immunity and Complement System

Innate Immunity

The body's first line of defense, present before infection and always active in healthy individuals to block and rapidly eliminate microbes.

Innate vs. Adaptive Immunity: Response & Memory

Innate provides a rapid response with no classical memory; adaptive has a slower initial response and develops immunologic memory.

Innate vs. Adaptive Immunity: Recognition & Diversity

Innate recognizes common molecular patterns with limited receptor diversity; adaptive recognizes specific antigens with highly diverse receptors.

Layers of Innate Defense

Epithelial barriers, cellular recruitment, pathogen recognition, and activation of adaptive immunity.

Epithelial Barrier Components

Physical barriers (skin, mucosa), chemical barriers (antimicrobial peptides, lysozyme, acid), and biological barriers (normal microbiota).

PAMPs (Pathogen-Associated Molecular Patterns)

Conserved microbial structures (e.g., LPS, peptidoglycan, flagellin) that stimulate innate immunity.

DAMPs (Damage-Associated Molecular Patterns)

Molecules associated with damaged or dying cells (e.g., HMGB1, extracellular ATP) that stimulate innate immunity.

PRRs (Pattern-Recognition Receptors)

Receptors of innate immunity (like TLRs, NLRs, RLRs) that recognize PAMPs and DAMPs.

Innate Tolerance to Healthy Cells

Innate receptors evolved to target microbial/damaged structures only, and healthy cells express surface molecules that block innate responses.

Toll-Like Receptors (TLRs)

Cell-surface PRRs that bind microbial proteins/lipids and activate transcription factors like NF-kB to stimulate inflammatory/antiviral responses.

NOD-Like Receptors (NLRs)

Cytosolic PRRs that sense DAMPs and PAMPs inside cells to promote inflammation.

RIG-I-Like Receptors (RLRs)

Cytosolic proteins that sense viral RNA and induce the production of type I interferons.

Cardinal Signs of Inflammation

Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain), and Functio laesa (loss of function).

Acute Inflammation Overview

Consists of vasodilation, increased vascular permeability, and leukocyte recruitment to sites of infection or injury.

Leukocyte Recruitment Steps

Margination, rolling, adhesion, transmigration (diapedesis), and chemotaxis to the site of infection.

Cells of Innate Immunity

Neutrophils, macrophages, dendritic cells, natural killer (NK) cells, and mast cells.

Natural Killer (NK) Cells

Lymphocytes that kill virus-infected and stressed cells using perforin and granzymes, and secrete IFN-gamma.

Steps of Phagocytosis

Recognition/attachment, engulfment, phagosome formation, phagolysosome formation, and microbial killing/degradation.

Opsonization

The coating of microbes by molecules (opsonins) to enhance phagocytosis.

Antiviral Innate Immunity

Mediated primarily by Type I Interferons to protect cells from viral replication.

Innate Activation of Adaptive Immunity

Dendritic cells recognize microbes, capture antigens, migrate to lymph nodes, and present antigens to T cells.

The Complement System

A cascade of plasma and membrane proteins that promote inflammation, enhance phagocytosis, and cause microbial lysis.

Three Complement Pathways

Classical pathway (triggered by antibodies), Lectin pathway (triggered by mannose-binding lectin), and Alternative pathway (spontaneous microbial activation).

Convergence of Complement Pathways

All three complement pathways converge at the central component, C3.

C3 Cleavage Products (C3a and C3b)

C3a promotes inflammation (vascular permeability, mast cell degranulation); C3b acts as a major opsonin and forms C5 convertase.

C5 Cleavage Products (C5a and C5b)

C5a is a potent inflammatory mediator and chemotactic factor; C5b initiates Membrane Attack Complex (MAC) formation.

Membrane Attack Complex (MAC)

Formed by C5b, C6, C7, C8, and polymerizing C9 proteins to create pores and lyse target cells (C5b-9).

Three Major Functions of Complement (OIL)

Opsonization, Inflammation, and Lysis.

Complement Regulation on Host Cells

Regulatory proteins (like Factor H, CD55, CD59) protect host cells from accidental complement attack and lysis.

C3 Deficiency Clinical Association

Associated with severe and recurrent bacterial infections.

C5-C9 Deficiency Clinical Association

Associated with recurrent Neisseria infections.

Loss of CD55/CD59

Results in paroxysmal nocturnal hemoglobinuria due to unregulated complement activity on blood cells.