Innate Immunity: Principles and Mechanisms (Chapter 11 Study Notes)

Innate Immunity: Principles and Mechanisms

Overview of Immune Responses

The immune system protects the body from pathogens through coordinated physiological processes. Immunity is divided into two main branches: innate immunity (inborn, nonspecific) and adaptive immunity (acquired, specific). Both branches share the abilities to recognize diverse pathogens, eliminate invaders, and distinguish self from non-self antigens.

• Innate Immunity: Present in all eukaryotes, provides immediate, nonspecific defense.

• Adaptive Immunity: Found only in vertebrates, matures over time, is highly specific, and exhibits memory.

Comparison of Innate and Adaptive Immunity

Innate and adaptive immunity differ in their mechanisms, response times, and specificity. The following table summarizes their key features:

Feature	Innate Immunity	Adaptive Immunity
Response time	Immediate	4–7 days
Organisms	All eukaryotes	Only vertebrates
Distinguishes self from foreign	Yes	Yes
Kills invaders	Yes	Yes
Effective against diverse threats	Yes	Yes
Tailors response to specific antigen	No	Yes
Memory	No	Yes

Normal Microbiota and Immune System Development

Role of Normal Microbiota

Normal microbiota are symbiotic microbes that inhabit the body and play a crucial role in shaping immune responses. They help train the immune system to distinguish between harmful and harmless agents, and their disruption can lead to immune confusion, allergies, or autoimmunity.

• Hygiene Hypothesis: Suggests that reduced microbial exposure may negatively affect immune development.

• Germ-free animal studies show underdeveloped immune systems without microbiota.

First-Line Defenses: Preventing Pathogen Entry

Types of First-Line Defenses

First-line defenses are barriers that prevent pathogen entry and are categorized as mechanical, chemical, or physical barriers.

• Mechanical Barriers: Rinse, flush, or trap pathogens (e.g., tears, urine, saliva, mucus, mucociliary escalator, earwax).

• Chemical Barriers: Directly attack invaders or create hostile environments (e.g., lysozyme, stomach acid, skin acidity, fatty acids, antimicrobial peptides).

• Physical Barriers: Structures that physically block entry (e.g., skin, epithelial tissue).

Antimicrobial Peptides (AMPs)

AMPs are proteins that destroy a wide range of pathogens. They can stimulate leukocytes, modulate inflammation, and directly disrupt microbial membranes or intracellular processes.

Skin as a Physical Barrier

The skin is a critical physical barrier composed of tightly packed, dead epithelial cells enriched with proteins and lipids, forming a water-resistant layer that blocks pathogen entry.

Second-Line Defenses: Cellular and Molecular Responses

Leukocytes and Molecular Factors

When first-line defenses are breached, second-line defenses involving leukocytes (white blood cells) and molecular factors are activated to eliminate invaders.

Lymphatic System

The lymphatic system collects, circulates, and filters body fluids, playing a vital role in immune surveillance and response. Lymph nodes filter lymph, while the spleen filters blood and removes damaged erythrocytes.

Formed Elements of Blood

Blood contains erythrocytes (red blood cells), leukocytes (immune cells), and platelets (involved in clotting and confining pathogens).

Primary and Secondary Lymphoid Tissues

• Primary lymphoid tissues: Sites of immune cell production and maturation (bone marrow, thymus).

• Secondary lymphoid tissues: Sites where immune responses are initiated (lymph nodes, spleen, MALT).

Leukocytes: Types and Functions

Classification of Leukocytes

Leukocytes are classified as granulocytes (with cytoplasmic granules) or agranulocytes (without granules). Major types include neutrophils, eosinophils, basophils, mast cells, monocytes, macrophages, dendritic cells, and lymphocytes.

Granulocytes

• Neutrophils: Most abundant, first responders, phagocytize pathogens, release AMPs.

• Eosinophils: Combat parasites, involved in allergies, moderate phagocytic activity.

• Basophils: Release histamine, involved in allergic responses, rare in circulation.

• Mast Cells: Reside in tissues, release histamine, fight parasites, activate adaptive immunity.

Agranulocytes

• Monocytes: Largest WBCs, migrate into tissues to become macrophages.

• Macrophages: Highly phagocytic, reside in tissues or wander, destroy pathogens.

• Dendritic Cells: Highly phagocytic, present antigens to T cells, prevent autoimmunity.

• Lymphocytes: Include NK cells (innate), B cells, and T cells (adaptive).

Molecular Second-Line Defenses

Cytokines

Cytokines are signaling proteins that coordinate immune responses, including inflammation, fever, leukocyte recruitment, and tissue repair. Major types include chemokines, interleukins, interferons, and tumor necrosis factors.

Cytokine Type	Examples	Functions
Chemokines	Monocyte chemoattractant protein-1	Recruit WBCs, wound healing, blood vessel formation
Interleukins (IL-1, IL-2)	IL-1, IL-2	Regulate inflammation, fever, T cell development
Interferons	IFN-α, IFN-β, IFN-γ	Antiviral responses, activate macrophages
Tumor necrosis factors	TNF-α	Induce inflammation, kill tumor cells, fever

Iron-Binding Proteins

Iron-binding proteins (hemoglobin, ferritin, lactoferrin, transferrin) limit free iron to restrict bacterial growth. Some pathogens have evolved mechanisms to acquire iron, such as producing siderophores or lysing red blood cells.

Complement System

The complement system consists of over 30 proteins that enhance immune responses through a cascade mechanism. Activation occurs via three pathways: classical (antibody-triggered), alternative (direct pathogen interaction), and lectin (mannose-binding lectin). Outcomes include opsonization, membrane attack complex (cytolysis), and inflammation.

Inflammation and Fever

Inflammation

Inflammation is a key innate response to tissue damage or infection, with three main goals: recruit immune defenses, limit pathogen spread, and promote tissue repair. The process occurs in three phases: vascular changes, leukocyte recruitment, and resolution.

• Vascular changes: Vasodilation, increased permeability, exudate formation (mediated by histamine, kinins, eicosanoids).

• Leukocyte recruitment: Margination and diapedesis allow leukocytes to exit vessels and reach infection sites.

• Resolution: Inflammation is toned down, tissue repair begins, and pus may form.

Fever

Fever (pyrexia) is a systemic response to infection, induced by pyrogens (e.g., bacterial toxins, cytokines) that signal the hypothalamus to raise body temperature. Fever enhances immune efficiency but can be dangerous if too high.

• Low-grade fever: Protective, enhances immune responses.

• High fever (>40.5°C): Medical emergency, can cause protein denaturation and death.

Fever Type	Description
Fever of undetermined origin (FUO)	≥38.3°C for >3 weeks, no clear cause
Intermittent	Elevates, returns to normal daily
Pel–Ebstein	3–10 days fever, then similar nonfever period
Relapsing	Recurrent episodes, days/weeks apart
Remittent	Elevated, fluctuates, never normal
Sustained	Consistently elevated, minimal fluctuation
Tertian	Fever on 1st and 3rd days (malaria)
Quartan	Fever on 1st and 4th days (malaria)

Clinical Application: Case Study

Case Summary

A 5-year-old boy with recurrent infections was diagnosed with bacterial meningitis caused by Streptococcus pneumoniae despite vaccination. He was found to have a deficiency in mannose-binding lectin (MBL), affecting his lectin pathway of complement activation.

• Key findings: Low MBL levels, recurrent pyrogenic infections, normal adaptive response to vaccines expected.

• Clinical implications: Early infection detection and prompt treatment are critical; MBL deficiency impairs innate immunity but not adaptive vaccine response.

Key Concepts Illustrated by the Case

• Differential WBC count: Likely shows increased neutrophils due to bacterial infection.

• Fever mechanism: Pyrogens induce cytokine release, signaling the hypothalamus to raise temperature; antipyretics inhibit prostaglandin synthesis.

• First-line defenses breached: Pathogen overcame mechanical, chemical, and physical barriers; second-line defenses (phagocytes, complement) were activated.

• Hemochromatosis check: To rule out iron overload, which increases infection risk.