Innate Immunity: Nonspecific Defenses of the Host (Chapter 16) – Study Notes

Innate Immunity: Nonspecific Defenses of the Host

I. The Concept of Immunity

Immunity refers to the ability of an organism to resist infection or disease. The immune system is divided into two main types: innate (nonspecific) and adaptive (specific) immunity.

• Innate Immunity: Present at birth; provides immediate, nonspecific defense against pathogens.

• Adaptive Immunity: Develops after exposure to specific antigens; involves memory and specificity.

• Toll-like receptors (TLRs): Proteins on host cells that recognize pathogen-associated molecular patterns (PAMPs) and trigger immune responses.

Additional info: Innate immunity includes physical, chemical, and cellular defenses that act as the first and second lines of defense.

II. Body's Defense: Two Types

• Nonspecific (Innate) Immunity: Includes barriers, phagocytes, inflammation, fever, and antimicrobial substances.

• Specific (Adaptive) Immunity: Involves lymphocytes (T cells and B cells) and the production of antibodies.

III. Body's First Line of Defense

A. Physical (Mechanical) Factors

• Intact Skin: Acts as a physical barrier; consists of epidermis and dermis.

• Mucous Membranes: Line respiratory, gastrointestinal, and genitourinary tracts; trap microbes.

• Lacrimal Apparatus: Produces tears to wash away microbes from the eyes.

• Saliva: Washes microbes from teeth and mouth.

• Mucus: Traps microbes in respiratory and GI tracts.

• Urine Flow: Flushes microbes out of the genitourinary tract.

• Vaginal Secretions: Remove microbes from the female body.

• Peristalsis, Defecation, Vomiting: Expel pathogens and toxins.

B. Chemical Factors

• Sebum: Oily substance that inhibits microbial growth.

• Low pH (3-5) of Skin: Discourages growth of many microbes.

• Lysozyme: Enzyme in perspiration, tears, saliva, and urine that destroys bacterial cell walls.

• Gastric Juice: High acidity (pH 1.2-3.0) destroys bacteria and toxins in the stomach.

C. Normal Flora

• Microbial antagonism: Normal microbiota compete with pathogens, altering the environment and producing substances harmful to pathogens.

• Examples: Escherichia coli, Lactobacillus, Staphylococcus

IV. Formed Elements in Blood

A. Leukocytes (White Blood Cells)

Leukocytes are crucial for immune responses and are classified as granulocytes or agranulocytes.

Type	Function
Neutrophils	Phagocytosis; most abundant, especially in bacterial infections
Basophils	Produce histamine; involved in inflammation
Eosinophils	Phagocytosis; increased in parasitic infections and allergies
Monocytes	Phagocytosis after maturing into macrophages
Dendritic Cells	Initiate adaptive immunity
Lymphocytes	Adaptive immunity; B cells (antibody production), T cells (cell-mediated immunity)

Differential White Count: The proportion of different leukocytes changes during infection.

V. Phagocytosis

A. Definition

Phagocytosis is the ingestion of microbes or particles by phagocytes (e.g., neutrophils, macrophages, dendritic cells).

B. Actions of Phagocytic Cells

• Neutrophils: Most important in early infection.

• Macrophages: Derived from monocytes; become active in tissues.

• Fixed Macrophages: Reside in specific tissues (e.g., liver, lungs).

• Free Macrophages: Roam tissues and gather at sites of infection.

C. Stages of Phagocytosis

1. Chemotaxis: Chemical attraction of phagocytes to microbes.

2. Adherence: Attachment of phagocyte to microbe via TLRs and PAMPs.

3. Ingestion: Microbe is engulfed by phagocyte, forming a phagosome.

4. Digestion: Phagosome fuses with lysosome; enzymes digest microbe.

D. Microbial Evasion of Phagocytosis

• Capsules: Prevent adherence.

• M protein: Inhibits phagocyte attachment.

• Leukocidins: Kill phagocytes.

• Membrane attack complex resistance: Prevents lysis.

• Escape from phagosome: Shigella, Listeria

• Prevent phagolysosome formation: Mycobacterium

• Biofilms: Protect microbes from phagocytes.

VI. Inflammation

Inflammation is a local response to cell damage, characterized by redness, heat, swelling, and pain.

• Functions: Destroy and remove injurious agents, confine damage, and repair tissue.

Stages of Inflammation

1. Vasodilation: Increased blood flow and permeability.

2. Phagocyte Migration: Phagocytes move to site of injury.

3. Tissue Repair: Restoration of damaged tissue.

VII. Fever

Fever is a systemic response to infection, often caused by bacterial toxins or viruses.

• Endotoxins: Stimulate cytokine release (e.g., interleukin-1, TNF-α).

• Benefits: Inhibits microbial growth, increases immune reactions, speeds up tissue repair.

VIII. Antimicrobial Substances

A. Complement System

The complement system consists of over 30 serum proteins that enhance immune responses.

• Classical Pathway: Activated by antibodies binding to antigens.

• Alternative Pathway: Activated by pathogen surfaces.

• Lectin Pathway: Activated by lectin binding to microbial carbohydrates.

Pathway	Trigger	Key Steps
Classical	Antibody-antigen complex	C1 activation, cascade, C3 cleavage
Alternative	Pathogen surface	Factor B, D, P, C3 activation
Lectin	Lectin binding to carbohydrates	MBL activation, C2/C4 cleavage, C3 activation

• Outcomes: Cytolysis, opsonization, inflammation

B. Interferons (IFN)

• Alpha and Beta Interferons: Produced in response to viral infection; inhibit viral replication.

• Gamma Interferon: Activates macrophages and enhances antigen presentation.

• Cell-specific, not virus-specific: Interferons act on host cells, not directly on viruses.

C. Antimicrobial Peptides

• Short peptides that inhibit microbial growth by disrupting cell membranes or interfering with DNA/RNA.

IX. Summary Table: Leukocytes and Their Functions

Leukocyte Type	Granulocyte/Agranulocyte	Main Function
Neutrophil	Granulocyte	Phagocytosis; first responder to infection
Basophil	Granulocyte	Histamine production; inflammation
Eosinophil	Granulocyte	Parasitic infections; allergy response
Monocyte/Macrophage	Agranulocyte	Phagocytosis; antigen presentation
Lymphocyte (B/T cell)	Agranulocyte	Adaptive immunity; antibody and cell-mediated responses

X. Key Equations and Terms

• Phagocytosis Equation: $\text{Phagocyte} + \text{Microbe} \rightarrow \text{Phagosome} \rightarrow \text{Phagolysosome} \rightarrow \text{Digestion}$

• Complement Activation: $\text{C3} \rightarrow \text{C3a} + \text{C3b}$

XI. Example Applications

• Skin as a Barrier: Prevents entry of pathogens; damage increases infection risk.

• Fever: Elevated body temperature can inhibit microbial growth and enhance immune function.

• Complement Deficiency: Increased susceptibility to infections.

Additional info: These notes expand on the original outline, providing definitions, examples, and tables for clarity and exam preparation.