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Defenses Against Disease

Introduction

The human body is constantly exposed to a wide variety of microbes, some of which are pathogenic and can cause disease. To protect itself, the body has evolved a complex immune system with multiple lines of defense, ranging from physical barriers to highly specific adaptive responses. This chapter explores the mechanisms of immunity, the cells and molecules involved, and what happens when the immune system malfunctions.

Three Lines of Defense

Overview of Immune Defenses

• Nonspecific External Barriers: Physical and chemical barriers such as skin and mucous membranes that prevent pathogen entry.

• Innate Immune Response: Rapid, nonspecific responses including phagocytic cells, inflammation, and fever.

• Adaptive Immune Response: Highly specific responses involving lymphocytes (B cells and T cells) that recognize and remember specific pathogens.

Nonspecific Defenses

External Barriers

The first line of defense consists of anatomical and chemical barriers that prevent pathogens from entering the body.

• Skin: Acts as a physical barrier; produces secretions (sweat, sebum) containing natural antibiotics like lactic acid.

• Mucous Membranes: Line the digestive, respiratory, and urogenital tracts; secrete mucus that traps microbes.

• Microbiome: Harmless microbes on the skin and in the gut outcompete pathogens.

Internal Nonspecific Defenses

• Phagocytes: White blood cells (macrophages, neutrophils, dendritic cells) that engulf and destroy pathogens.

• Natural Killer Cells: Destroy virus-infected and cancerous cells by recognizing abnormal or missing MHC proteins.

• Inflammatory Response: Tissue damage triggers mast cells to release histamine, increasing blood flow and attracting phagocytes.

• Fever: Pyrogens raise body temperature, enhancing immune cell activity and inhibiting pathogen growth.

Adaptive (Specific) Immunity

Key Components

The adaptive immune system is characterized by specificity and memory. It involves specialized lymphocytes and is distributed throughout the body in organs such as the bone marrow, thymus, spleen, lymph nodes, and tonsils.

• B cells: Mature in bone marrow; produce antibodies.

• T cells: Mature in thymus; include helper T cells, cytotoxic T cells, and regulatory T cells.

• Antigen-presenting cells: Macrophages and dendritic cells that display antigens to lymphocytes.

• Proteins: Cytokines (cell signaling), antibodies (recognition and neutralization), and complement proteins (assist in killing microbes).

Recognition of Invaders

• Antigens: Large, complex molecules (often proteins or polysaccharides) that trigger immune responses.

• Antibodies: Y-shaped proteins produced by B cells; each has unique variable regions that bind specific antigens.

• T-cell Receptors: Proteins on T cells that recognize antigens presented by other cells.

Types of Antibodies

• IgG: Most common in blood; crosses placenta.

• IgA: Found in secretions (saliva, milk, mucus).

• IgM: First produced in response; pentameric structure.

• IgE: Involved in allergic reactions.

• IgD: Functions as a B-cell receptor.

Self vs. Non-Self Recognition

• MHC Proteins: Unique to each individual; help immune cells distinguish self from non-self.

• Clonal Deletion: Self-reactive B and T cells are eliminated during development.

• Regulatory T Cells: Suppress any remaining self-reactive lymphocytes.

Immune Responses

Humoral Immunity (Antibody-Mediated)

B cells produce antibodies that circulate in body fluids and bind to antigens on pathogens, neutralizing them or marking them for destruction.

• Clonal Selection: Antigen binding stimulates B cells to divide and differentiate into plasma cells (antibody-secreting) and memory B cells.

• Antibody Actions:

  • Neutralization: Antibodies block active sites of toxins or viruses.

  • Opsonization: Antibodies coat pathogens, enhancing phagocytosis.

  • Complement Activation: Antibodies trigger complement proteins to lyse pathogens.

Cell-Mediated Immunity

Cytotoxic T cells recognize and destroy infected or cancerous cells by binding to antigens presented on their surfaces and releasing enzymes that induce cell death.

• Helper T Cells: Stimulate both B cells and cytotoxic T cells by releasing cytokines.

Immunological Memory

After an infection, memory B and T cells persist in the body, enabling a faster and stronger response upon re-exposure to the same pathogen. This is the basis for acquired immunity and vaccination.

Medical Assistance to Immunity

Antimicrobial Drugs and Vaccines

• Antibiotics: Kill or inhibit bacteria, but are ineffective against viruses.

• Antiviral Drugs: Target specific stages of viral replication.

• Vaccines: Expose the immune system to antigens, generating memory cells and long-term immunity without causing disease.

Immune System Malfunctions

Allergies

Allergies are inappropriate immune responses to harmless substances (allergens). IgE antibodies bind to mast cells, which release histamine upon allergen exposure, causing inflammation and symptoms such as sneezing and congestion.

Autoimmune Diseases

• Autoimmunity: The immune system attacks the body's own cells (e.g., type 1 diabetes, rheumatoid arthritis, multiple sclerosis).

• Treatment: Immunosuppressive drugs can reduce symptoms but increase susceptibility to infections.

Immune Deficiency Diseases

• Genetic Deficiencies: Such as severe combined immune deficiency (SCID), where few or no immune cells are produced.

• Acquired Deficiencies: Caused by factors like HIV infection, chemotherapy, or malnutrition.

• AIDS: Caused by HIV, which destroys helper T cells, crippling both humoral and cell-mediated immunity.

Immune System and Cancer

Immune Surveillance and Cancer

• Recognition: Natural killer cells and cytotoxic T cells can detect and destroy cancerous cells by recognizing abnormal surface proteins.

• Immune Evasion: Some cancer cells avoid detection by not displaying recognizable antigens.

Immunotherapy

• CAR-T Cell Therapy: Patient's T cells are genetically engineered to target cancer cells and reintroduced to the body.

• Checkpoint Inhibitors: Drugs that block proteins which restrain T cell activity, enhancing immune attack on tumors.

• Oncolytic Viruses: Viruses engineered to infect and kill cancer cells.

Comparative Summary Tables

Innate vs. Adaptive Immunity

Characteristic	Innate Immune Response	Adaptive Immune Response
Specificity of response	Nonspecific	Specific for particular microbes
Speed of first response	Immediate	Delay of several days to 2 weeks
Magnitude of second response	Identical to first	Enormously enhanced; usually no symptoms
Distribution	Invertebrates and vertebrates	Vertebrates only

Cellular Arsenal Against Disease

Type of Cell	Function
Neutrophils	Engulf invading microbes (innate)
Dendritic cells	Engulf microbes, present antigens (innate)
Macrophages	Engulf microbes, present antigens (innate)
Natural killer cells	Destroy infected or cancerous cells (innate)
Mast cells	Release histamine, inflammation (innate)
B cells	Produce antibodies (adaptive)
Memory B cells	Provide future immunity (adaptive)
Plasma cells	Secrete antibodies (adaptive)
T cells	Regulate or kill infected/cancerous cells (adaptive)
Cytotoxic T cells	Destroy infected/cancerous cells (adaptive)
Helper T cells	Stimulate B and cytotoxic T cells (adaptive)
Memory T cells	Provide future immunity (adaptive)
Regulatory T cells	Suppress self-reactive lymphocytes (adaptive)