Immunology and Disease: Innate and Adaptive Body Defenses

Immunology and Disease

Introduction to Immunology

Immunology is the study of the body's defense mechanisms against pathogens, including bacteria, viruses, fungi, and parasites. The immune system is divided into two main branches: innate (nonspecific) defenses and adaptive (acquired, specific) defenses. These systems work together to protect the body from infection and disease.

Innate Defenses

Physical and Chemical Barriers

Innate defenses are the body's first line of defense and act nonspecifically against a wide range of pathogens.

• Epidermis: The outermost layer of skin, composed of closely joined cells forming a tight seal that prevents pathogen entry.

• Stratum corneum: The outer layer of dead epidermal cells rich in keratin, a protein that makes it difficult for toxins and microbes to penetrate. This layer is constantly shed, removing attached bacteria.

• Sweat and oily secretions: Help sweep pathogens away and create an acidic environment inhospitable to microbes.

• Defensins: Antimicrobial proteins present in the skin and mucosa that disrupt microbial membranes.

• Mucus membranes: Line body cavities and secrete thick mucus to trap pathogens. Cilia in the trachea move mucus to the pharynx for removal.

• Tears and saliva: Wash away microbes and contain lysozyme, an enzyme that breaks down bacterial cell walls.

• Urinary tract: Regularly flushed by urine, which contains urea that inhibits microbial growth.

• Stomach acid: Highly acidic environment destroys ingested pathogens.

• Gut microbiome: Beneficial bacteria in the large intestine outcompete and exclude pathogenic bacteria.

Internal Defenses

If pathogens breach physical and chemical barriers, the body employs internal defenses that are also nonspecific.

• Defensive cells: White blood cells that destroy pathogens by phagocytosis or cytotoxic activity.

• Defensive chemicals: Substances that interfere with or destroy pathogens, alert other immune cells, and prevent the spread of infection.

• Inflammation: Localized response that promotes healing by increasing blood flow and immune cell access to the site of infection.

• Fever: Systemic response that raises body temperature to inhibit pathogen growth and enhance immune function.

Blood Components

• Plasma: Fluid portion containing proteins, nutrients, and waste products.

• Red blood cells (erythrocytes): Carry oxygen.

• White blood cells (leukocytes): Key players in immune defense.

• Platelets: Involved in blood clotting, which prevents blood loss and limits infection spread.

Innate Defensive White Blood Cells

• Neutrophils: Small, phagocytic cells that are first responders to infection and specialize in neutralizing bacteria.

• Monocytes/Macrophages: Larger cells that transform into macrophages, which perform general phagocytosis, neutralize bacteria, attack larger pathogens, and clean up damaged tissue.

• Eosinophils: Attack larger pathogens, such as parasites, by releasing destructive enzymes.

• Natural Killer (NK) cells: Destroy infected or defective self cells (e.g., virus-infected or tumor cells) by recognizing abnormal signal proteins and inducing cell lysis.

Defensive Chemicals

• Interferons: Proteins released by stressed or infected cells (especially viral infections) that activate immune cells, induce neighboring cells to destroy RNA, and promote apoptosis to limit viral spread.

• Complement system: A group of about 20 proteins circulating in the blood in inactive form. When activated, they destroy pathogen cell membranes, enhance phagocytosis, and stimulate inflammation.

Inflammatory Response

• Characterized by redness, heat, swelling, and pain.

• Initiated by histamine released from mast cells in response to injury or infection.

• Redness: Due to blood vessel dilation, increasing blood flow and bringing white blood cells to the site.

• Heat: Increased blood flow raises local temperature, enhancing immune cell activity and tissue repair.

• Swelling: Increased permeability of blood vessels allows plasma, white blood cells, and proteins to enter tissues.

• Pain: Caused by swelling pressing on nerves, bacterial toxins, and prostaglandins (which can be inhibited by aspirin).

Fever

• Caused by pyrogens, chemicals that raise the hypothalamic set point for body temperature.

• Pyrogens can be exogenous (from pathogens) or endogenous (produced by the body).

• Symptoms include chills, shivering, and reduced blood flow to the skin. When fever breaks, sweating occurs.

• Fever reduces bacterial growth by causing the liver to sequester iron (needed for bacterial division) and increases metabolism to fight infection.

• Fever above 40°C is dangerous and can cause cellular damage.

Adaptive (Acquired) Immune Response

Overview

The adaptive immune response is highly specific, targeting particular pathogens. It recognizes, destroys, and remembers pathogens for faster response upon re-exposure.

• Lymphocytes are the main cells of the adaptive immune system.

• T lymphocytes (T cells): Produced in bone marrow, mature in the thymus.

• B lymphocytes (B cells): Produced and mature in bone marrow.

• Mature lymphocytes circulate throughout the body, especially in the lymphatic system.

T Lymphocytes

• Recognize self vs. invader using MHC markers (major histocompatibility complex) present on all body cells.

• Recognize antigens: molecules (usually proteins or carbohydrates) specific to pathogens, recognized by their shape.

• Upon encountering an antigen, T cells activate an immune response and can destroy infected cells.

• Helper T cells: Activated by antigen-presenting cells (e.g., macrophages) and stimulate other immune cells.

• Cytotoxic T cells: Directly kill infected or abnormal cells.

• Memory T cells: Long-lived cells that provide rapid response upon re-exposure to the same antigen.

B Lymphocytes

• Produce antibodies that react to specific molecules (antigens) and neutralize pathogens.

• Upon activation, B cells differentiate into plasma cells (which secrete antibodies) and memory B cells (which provide long-term immunity).

Steps of the Adaptive Immune Response

Step	Description
1. Threat	Foreign cell or molecule enters the body.
2. Detection	Macrophage detects and engulfs the foreign cell or molecule.
3. Alert	Macrophage presents antigen to helper T cell, activating it.
4. Alarm	Helper T cell activates both B and T cells to fight the specific antigen.
5. Building specific defenses	B cells divide to form plasma cells (antibody production); T cells divide to form cytotoxic T cells (cell-mediated attack).
6. Defense	Antibodies bind to antigens; cytotoxic T cells destroy infected cells.
7. Continued surveillance	Memory cells remain for rapid future response.
8. Withdrawal of forces	Once the antigen is eliminated, immune response subsides.

Antibody Structure and Function

• Antibodies are Y-shaped proteins with two antigen-binding sites.

• Functions include:

  • Precipitation: Clumping antigens for easier phagocytosis.

  • Lysis: Activating the complement system to destroy pathogens.

  • Attraction: Recruiting phagocytic cells to the site of infection.

  • Neutralization: Binding to toxins or viruses to block their activity.

Types of Immunity

• Active immunity: Body produces memory B and T cells after exposure to an antigen (through infection or vaccination).

• Passive immunity: Antibodies are acquired from another source (e.g., maternal antibodies via placenta or milk, or injection of prepared antibodies); no memory cells are produced.

Vaccines

• Vaccines may contain pathogen molecules, dead or weakened pathogens, or mRNA that instructs cells to produce pathogen molecules (antigens).

• Vaccination stimulates active immunity without causing disease.

Immune System Disorders

Autoimmune Disorders

• Occur when the immune system fails to distinguish self from non-self, attacking the body's own cells.

• Organ-specific: T cells attack specific organs (e.g., Hashimoto's thyroiditis, Type I diabetes).

• Non-organ-specific: B cells produce antibodies that attack various tissues (e.g., lupus, rheumatoid arthritis).

• Acquired: Some autoimmune diseases are triggered by infections with antigens resembling self molecules (e.g., rheumatic fever after strep throat).

Allergies

• Immune response to harmless substances (allergens) such as pollen.

• First exposure produces antibodies that bind to mast cells; subsequent exposure causes mast cells to release histamine, leading to swelling, irritation, and mucus production.

• Anaphylactic shock: Severe, systemic allergic reaction causing blood vessel dilation and dangerous drop in blood pressure. Treated with epinephrine (adrenaline) to constrict blood vessels.

Summary Table: Innate vs. Adaptive Defenses

Feature	Innate Defenses	Adaptive Defenses
Specificity	Nonspecific	Highly specific
Response Time	Immediate	Slower (days)
Memory	None	Has memory
Main Cells	Neutrophils, macrophages, NK cells	B and T lymphocytes
Main Barriers	Skin, mucous membranes, secretions	Antibodies, cytotoxic T cells

Key Terms

• Pathogen: Disease-causing organism.

• Self vs. Non-self: Immune system's ability to distinguish body cells from foreign invaders.

• Antigen: Molecule recognized as foreign by the immune system.

• Antibody: Protein produced by B cells that binds to specific antigens.

• MHC markers: Proteins on cell surfaces that identify cells as "self."

• Phagocytosis: Process by which cells engulf and digest pathogens.

• Lyse: To break down or destroy a cell membrane.