Innate Immunity: Nonspecific Defenses of the Host – Study Notes

Innate Immunity: Nonspecific Defenses of the Host

Introduction to Immunity

Immunity refers to the body's ability to resist or eliminate potentially harmful foreign materials or abnormal cells. The immune system is divided into two main branches: innate immunity and adaptive immunity.

• Innate Immunity: The first line of defense, present at birth, providing rapid, nonspecific responses to pathogens.

• Adaptive Immunity: Develops as a result of exposure to antigens, providing specific and long-lasting protection.

Example: Skin acting as a barrier is an innate defense, while antibody production after vaccination is adaptive immunity.

Toll-like Receptors (TLRs)

Toll-like receptors are proteins found on the surface of certain immune cells that recognize structurally conserved molecules derived from microbes. They play a crucial role in activating innate immune responses.

• TLRs bind to pathogen-associated molecular patterns (PAMPs) and trigger the release of cytokines that regulate immune responses.

Physical and Chemical Barriers

The skin and mucous membranes form the body's primary physical barriers against infection. These barriers are supported by various chemical factors.

Physical Factors

• Intact skin

• Mucous membranes

• Tears and saliva (washing action)

• Ciliary escalator in the respiratory tract

• Urine flow and vaginal secretions

Chemical Factors

• Low pH of skin (due to sebum)

• Lysosome in tears, saliva, and sweat

• Gastric juice (low pH in stomach)

• Transferrins in blood (bind iron)

• Antimicrobial peptides

Role of Normal Microbiota

Normal microbiota are the microorganisms that colonize the body without causing disease. They contribute to innate immunity by:

• Competing with pathogens for nutrients and attachment sites

• Producing substances harmful to pathogens

• Stimulating the host's immune system

Leukocytes: Classification and Functions

Leukocytes (white blood cells) are key players in the immune system. They are classified as granulocytes or agranulocytes based on the presence of granules in their cytoplasm.

• Granulocytes: Neutrophils, eosinophils, basophils

• Agranulocytes: Monocytes, lymphocytes (T cells, B cells, NK cells)

Types of White Blood Cells and Their Functions

Cell Type	Main Function
Neutrophils	Phagocytosis of bacteria and fungi
Eosinophils	Defense against parasites; role in allergies
Basophils	Release histamine during inflammation and allergic reactions
Monocytes	Differentiate into macrophages and dendritic cells; phagocytosis
Macrophages	Phagocytosis; antigen presentation
Dendritic cells	Antigen presentation to T cells
Lymphocytes (T cells)	Cell-mediated immunity
Lymphocytes (B cells)	Produce antibodies (humoral immunity)
Natural Killer (NK) cells	Destroy virus-infected and tumor cells

Additional info: Some sources group dendritic cells and macrophages as derivatives of monocytes.

Lymphatic vs. Blood Circulatory Systems

• Blood circulatory system: Circulates blood throughout the body, delivering oxygen and nutrients.

• Lymphatic system: Collects interstitial fluid (lymph), filters it through lymph nodes, and returns it to the bloodstream; important for immune surveillance.

Phagocytes and Phagocytosis

Phagocytes are cells that ingest and destroy microbes and debris. Phagocytosis is the process by which these cells engulf particles.

• Key phagocytes: Neutrophils, macrophages, dendritic cells

Stages of Phagocytosis

1. Chemotaxis: Phagocyte moves toward chemical signals from microbes.

2. Adherence: Phagocyte attaches to the microbe.

3. Ingestion: Microbe is engulfed into a phagosome.

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

5. Exocytosis: Waste materials are expelled.

Inflammation

Inflammation is a local response to tissue injury or infection, characterized by redness, heat, swelling, and pain.

Stages of Inflammation

1. Vasodilation and increased permeability of blood vessels

2. Phagocyte migration and phagocytosis

3. Tissue repair

Mediators of Inflammation

• Vasodilation: Increases blood flow to the area (redness, heat)

• Kinins, prostaglandins, leukotrienes: Promote vasodilation, increase permeability, attract phagocytes

Phagocyte Migration

• Phagocytes move from blood to tissues (diapedesis) in response to chemical signals (chemotaxis).

Fever

Fever is an abnormally high body temperature, often caused by infection.

• Caused by pyrogens (e.g., cytokines) that reset the hypothalamic thermostat.

• Effects: Inhibits microbial growth, increases metabolism, enhances immune responses.

The Complement System

The complement system is a group of proteins in blood that enhance immune responses.

• Major components: C1–C9 proteins

Three Pathways of Activation

• Classical pathway: Triggered by antibodies bound to antigens

• Alternative pathway: Triggered by microbial surfaces

• Lectin pathway: Triggered by mannose-binding lectin binding to pathogen surfaces

Consequences of Complement Activation

• Opsonization (enhanced phagocytosis)

• Inflammation

• Cytolysis (cell lysis via membrane attack complex)

Interferons (IFNs)

Interferons are cytokines that interfere with viral replication.

• IFN-α and IFN-β: Produced by virus-infected cells; induce antiviral proteins in neighboring cells.

• IFN-γ: Produced by T cells and NK cells; activates macrophages and enhances antigen presentation.

Comparison: IFN-α and IFN-β are mainly antiviral, while IFN-γ is more involved in immune regulation.

Iron-Binding Proteins

Iron-binding proteins (e.g., transferrin, lactoferrin, ferritin, hemoglobin) sequester iron, making it unavailable to microbes and thus inhibiting their growth.

Antimicrobial Peptides (AMPs)

AMPs are small proteins produced by various cells that have broad-spectrum antimicrobial activity. They disrupt microbial membranes, inhibit cell wall synthesis, and recruit immune cells.

• Examples: Defensins, cathelicidins