Innate Immunity, Inflammation, and Wound Healing

Three layers of human defense

Physiologic (surface) barriers, the inflammatory response, and adaptive (acquired) immunity.

First line of defense

Physical and biochemical barriers, including the skin, mucous membranes, and normal microbiome.

Biochemical barriers in secretions

Antibacterial peptides found in mucous secretions, perspiration, saliva, and tears.

Role of the normal microbiome

Commensal microorganisms protect by releasing biochemical compounds that prevent pathogen colonization and aid digestion.

Second line of defense

The inflammatory response: a rapid, nonspecific protective response occurring only in vascularized tissues.

Macroscopic hallmarks of inflammation

Redness, swelling, heat, pain, and loss of function.

Microscopic hallmarks of inflammation

Vasodilation, increased capillary permeability, and accumulation of fluid and cells.

Three key plasma protein systems of inflammation

The complement system, the clotting system, and the kinin system.

Complement system pathways

Classical (antibody-activated), lectin, and alternative pathways (non-antibody activated).

Key biologically potent complement products

C3b (opsonin), C3a (anaphylatoxin), and C5a (anaphylatoxin and chemotactic factor).

Clotting system functions

Stops bleeding, localizes microorganisms, and provides a meshwork for repair and healing.

Main product of the kinin system

Bradykinin, which causes vascular permeability, smooth muscle contraction, and pain.

Inactivating enzymes of inflammation

Carboxypeptidase, histaminase, kinase, and C1 inhibitor.

Primary cells initiating inflammation

Mast cells and macrophages.

Pattern Recognition Receptors (PRRs)

Receptors (like TLRs and NOD-like receptors) that recognize PAMPs and DAMPs to promote inflammation.

Mast cell inflammatory mediators

Preformed histamine and chemotactic factors from granules; synthesized prostaglandins, leukotrienes, and PAF.

Histamine action

Major vasoactive amine that increases vascular permeability via capillary dilation and endothelial cell retraction.

Macrophage cytokines

Biochemical mediators like TNF-α, interleukins, and interferons that regulate the inflammatory response.

TNF-α effects

Proinflammatory cytokine causing vascular changes, chemotaxis, cell proliferation, and systemic changes.

Key proinflammatory interleukins

Interleukin-1 (IL-1) and Interleukin-6 (IL-6), which contribute to leukocyte growth, differentiation, and fever.

Interferons function

Protective proteins produced by virus-infected cells that stimulate neighboring cells to resist viral infection.

Antiinflammatory cytokines

Cytokines such as TGF-β and IL-10 that downregulate the inflammatory response.

Neutrophils in inflammation

Polymorphonuclear neutrophils (PMNs) are the predominant phagocytic cells in early inflammation.

Monocyte-derived macrophages

Highly phagocytic cells predominant in the late inflammatory response that promote wound healing.

Steps of phagocytosis

Recognition/attachment, engulfment, phagosome formation, phagolysosome formation, and destruction.

Opsonins

Molecules like antibodies and C3b that coat antigens to enhance phagocytic binding and destruction.

Eosinophils primary role

Control the inflammatory response and destroy parasitic organisms.

Acute vs. chronic inflammation duration

Acute is self-limiting (8-10 days); chronic involves dense lymphocyte/macrophage infiltration and tissue damage.

Granuloma formation

Process where the body walls off and isolates microorganisms/foreign bodies that acute inflammation cannot remove.

Resolution vs. repair

Resolution returns tissue to normal structure; repair is healing by scar tissue formation.

Primary vs. secondary intention

Primary intention occurs with minimal tissue loss; secondary intention occurs with extensive damage, forming a scar.

Four phases of wound healing

Hemostasis, inflammation, proliferation, and remodeling/maturation.

Wound complications

Dehiscence (pulling apart at suture line) and contracture (structural deformity from excessive collagen shortening).

Four stages of infection

Incubation period, prodromal stage, invasion (acute illness) stage, and convalescence.

Exotoxins vs. Endotoxins

Exotoxins damage host cell membranes/proteins; endotoxins activate inflammation and produce fever.

Septicemia mechanism

Bacterial proliferation in blood releases vasoactive enzymes, causing hypotension and potential septic shock.

Viral replication strategy

Intracellular parasites utilizing host metabolic processes through a 7-step replication cycle.

HIV primary receptor and target

Envelope gp120 binds to CD4 and chemokine co-reactants on T-helper cells, macrophages, and dendritic cells.

AIDS hallmark finding

Severe decrease in CD4+ T-helper cells leading to opportunistic infections and cancers.

SARS-CoV-2 mechanism

Attaches to respiratory epithelial cells via spike protein, potentially triggering a deadly cytokine storm.

Fungal infections (Mycoses)

Occur as yeasts or molds; dermatophytes cause skin/hair/nail infections like ringworm and athlete's foot.

Parasitic transmission

Rarely human-to-human; mainly spread through vectors (mosquitoes) or contaminated water.

Antibiotic resistance mechanisms

Resistance gene transmission, enzyme degradation, antibiotic ejection, cell wall modification, and target modification.

Vaccines vs. Passive immunotherapy

Vaccines use antigen preparations to stimulate active immunity; passive immunotherapy administers preformed antibodies.