Study Guide: The Immune System – Innate and Adaptive Body Defenses

CH 21 The Immune System: Overview

General Functions and Structure

The immune system is a functional system that provides resistance to disease-causing microorganisms such as bacteria, fungi, and viruses. It is not an anatomical organ system, but rather a network of molecules and immune cells (especially lymphocytes) that reside in lymphoid tissues and circulate in body fluids. The body employs three lines of defense, acting both independently and cooperatively, to resist invasion and provide immunity.

• First Line of Defense: Surface barriers (skin and mucosae)

• Second Line of Defense: Innate internal defenses (inflammation, antimicrobial proteins, phagocytes)

• Third Line of Defense: Adaptive (specific) defense system (lymphocytes and antibodies)

Innate Defenses

Surface Barriers: First Line of Defense

Surface barriers include the skin and mucous membranes, along with their secretions. These barriers are highly effective for most microbes due to their structural and chemical properties.

• Keratin: Protein in the epidermis resistant to acids, bases, bacterial enzymes, and toxins

• Mucosae: Provide mechanical barriers within the body

• Acid Mantle: Acidity of skin, vaginal, and stomach secretions inhibits bacterial growth

• Enzymes: Lysozyme in saliva, respiratory mucus, and lacrimal fluid kills microbes; protein-digesting enzymes in stomach destroy pathogens

• Mucin: Sticky mucus traps microbes in digestive and respiratory tracts

• Defensins: Antimicrobial peptides secreted in response to barrier breach and inflammation

• Other Chemicals: Lipids in sebum and dermcidin in sweat are toxic to bacteria

Innate Internal Defenses: Second Line of Defense

If microbes breach the first line, the second line of defense is activated. This includes nonspecific cellular and chemical means such as phagocytes, natural killer cells, antimicrobial proteins, inflammation, and fever.

• Pattern Recognition Receptors: Identify pathogens by recognizing specific-shaped molecules (e.g., carbohydrates) found on them

• Toll-like Receptors (TLRs): Play a central role in triggering immune responses; humans have 11 TLRs

Phagocytes

Phagocytes are white blood cells that ingest and digest foreign invaders and cellular debris.

• Neutrophils: Most abundant phagocytes; phagocytize infectious material in tissues

• Macrophages: Most voracious phagocytes; can be free (wandering) or fixed (resident in organs)

Phagocytosis Process

Phagocytosis begins when phagocyte receptors bind to a particle, which is then pulled inside and enclosed within a membrane-lined vesicle (phagosome). The phagosome fuses with a lysosome to form a phagolysosome, where acidification and lysosomal enzymes digest the contents. Some pathogens resist these enzymes, requiring additional mechanisms such as the respiratory burst.

Natural Killer (NK) Cells

NK cells are large granular lymphocytes that police blood and lymph, targeting cells with abnormal surface proteins (e.g., lack of MHC). They kill cancer and virus-infected cells by inducing apoptosis and secrete chemicals that enhance inflammation.

Inflammation

Inflammation is a nonspecific response to tissue injury, caused by trauma, heat, chemicals, or infection.

• Benefits: Prevents spread of pathogens, disposes of debris, alerts adaptive immune system, sets stage for repair

• Cardinal Signs: Redness, heat, swelling, pain (sometimes impaired function)

• Inflammatory Chemicals: Histamine, kinins, prostaglandins, cytokines, complement proteins

• Vasodilation: Increases blood flow and capillary permeability, allowing exudate to seep into tissue

Phagocyte Mobilization

Four steps:

1. Leukocytosis: Increase in WBCs

2. Margination: Phagocytes cling to capillary walls

3. Diapedesis: Neutrophils squeeze between endothelial cells

4. Chemotaxis: WBCs move toward injured area

Interferons

Interferons are immune-modulating proteins produced by virus-infected cells. They interfere with viral replication in neighboring cells by stimulating production of proteins that block protein synthesis and degrade viral RNA.

Complement System

The complement system consists of at least 20 plasma proteins that circulate in an inactive state. When activated, complement amplifies inflammation and lyses certain bacteria and other cell types.

• Classical Pathway: Involves antibodies binding to pathogens

• Lectin Pathway: Lectins bind to specific sugars on microbes

• Alternative Pathway: Spontaneous activation on microbe surfaces

Fever

Fever is a systemic response to invading microbes. Pyrogens released by leukocytes and macrophages act on the hypothalamus to raise body temperature.

• Benefits: Enhances immune response, increases metabolic rate, suppresses bacterial growth

Adaptive Defenses

General Features

The adaptive immune system is a specific defensive system that targets and eliminates almost any pathogen. It consists of two overlapping arms:

• Humoral Immunity: Antibody-mediated, targets extracellular pathogens

• Cellular Immunity: Cell-mediated, targets infected, cancerous, or foreign cells

Antigens

Antigens are substances that trigger the adaptive immune response.

• Complete Antigens: Have immunogenicity and reactivity

• Haptens: Incomplete antigens that become immunogenic when attached to a protein carrier

• Antigenic Determinants: Parts of antigen that antibodies or lymphocyte receptors bind to

Self-Antigens: MHC Proteins

Self-antigens are proteins on body cell surfaces that are not antigenic to self but are antigenic to others. MHC proteins display peptides (self or foreign) and are essential for T cell recognition.

B and T Lymphocytes and Antigen-Presenting Cells

• B Lymphocytes: Provide humoral immunity

• T Lymphocytes: Provide cellular immunity

• Antigen-Presenting Cells (APCs): Present antigens to T cells

Lymphocyte Development, Maturation, and Activation

Five general steps:

1. Origin: Hematopoietic stem cells in red bone marrow

2. Maturation: Immunocompetence and self-tolerance in primary lymphoid organs

3. Seeding: Colonization of secondary lymphoid organs

4. Antigen Encounter and Activation: Clonal selection

5. Proliferation and Differentiation: Formation of effector and memory cells

Antigen-Presenting Cells (APCs)

• Dendritic Cells: Capture antigens and present them to T cells

• Macrophages: Present antigens and become activated phagocytes

• B Lymphocytes: Present antigens to helper T cells

Humoral Immunity

Clonal Selection of B Cells

Naive B cells are activated when their surface receptors bind to an antigen, leading to proliferation and differentiation into plasma cells (antibody-secreting) and memory cells.

Primary and Secondary Humoral Responses

• Primary Response: Occurs upon initial exposure; lag period of 3–6 days

• Secondary Response: Faster and more effective due to memory cells

Active and Passive Humoral Immunity

• Active Immunity: B cells produce antibodies (naturally via infection or artificially via vaccination)

• Passive Immunity: Antibodies are introduced (naturally via placenta/milk or artificially via injection)

Antibodies (Immunoglobulins)

Antibodies are proteins secreted by plasma cells, grouped into five classes: IgG, IgA, IgM, IgE, and IgD.

• Structure: Four polypeptide chains (two heavy, two light), variable and constant regions, antigen-binding sites

• Classes: Each class has different roles and locations

Antibody Roles

• Neutralization: Block sites on pathogens/toxins

• Agglutination: Clumping of antigens

• Precipitation: Formation of large complexes

• Complement Activation: Leads to cell lysis, inflammation, enhanced phagocytosis

Cellular Immunity

T Lymphocytes

T cells provoke a cellular immune response when presented with antigens.

• CD4 Cells: Become helper T cells or regulatory T cells

• CD8 Cells: Become cytotoxic T cells

MHC Proteins and Antigen Presentation

T cells respond only to processed fragments of antigens displayed by MHC proteins.

• MHC Class I: On all body cells except RBCs; display endogenous antigens

• MHC Class II: On APCs; display exogenous antigens

Activation and Differentiation of T Cells

T cell activation requires antigen binding and co-stimulation. Activated T cells proliferate and differentiate into effector and memory cells.

Roles of Specific Effector T Cells

• Helper T Cells: Mobilize both humoral and cellular immunity, activate B and T cells, secrete cytokines

• Cytotoxic T Cells: Directly attack and kill infected, cancerous, or foreign cells

• Regulatory T Cells: Suppress immune response, prevent autoimmunity

Immune System Disorders

Immunodeficiencies

• SCID: Severe combined immunodeficiency; deficit in B and T cells

• AIDS: Acquired immune deficiency syndrome; caused by HIV

Autoimmune Diseases

Occur when the immune system fails to distinguish self from foreign antigens, leading to destruction of self tissues. Examples include rheumatoid arthritis, myasthenia gravis, multiple sclerosis, Graves’ disease, type 1 diabetes mellitus, systemic lupus erythematosus, and glomerulonephritis.

Hypersensitivities

Immune responses to perceived threats that cause tissue damage.

• Immediate (Acute) Hypersensitivity: Allergies; mediated by IgE

• Subacute Hypersensitivity: Mediated by IgM and IgG

• Delayed Hypersensitivity: Mediated by T cells

Developmental Aspects of the Immune System

Immune System Development and Aging

• Immune system stem cells develop in liver and spleen during early weeks

• Bone marrow becomes primary source later

• Efficiency wanes with age, increasing susceptibility to infection, cancer, and autoimmune diseases

• Thymus atrophies after puberty, reducing naive T and B cell production

Summary Table: Key Differences Between Innate and Adaptive Defenses

Feature	Innate Defenses	Adaptive Defenses
Specificity	Nonspecific	Specific (targets particular antigens)
Response Time	Immediate	Delayed (requires priming)
Components	Physical barriers, phagocytes, NK cells, inflammation, complement, fever	B and T lymphocytes, antibodies, APCs
Memory	No memory	Immunological memory

Summary Table: Immunoglobulin Classes

Class	Structure	Main Function	Location
IgG	Monomer	Main antibody of secondary response; crosses placenta	Blood, lymph
IgA	Dimer/Monomer	Protects mucosal surfaces	Secretions (saliva, tears, milk)
IgM	Pentamer	First antibody released; potent agglutinating agent	Blood, lymph
IgE	Monomer	Triggers histamine release; involved in allergies	Skin, mucosae
IgD	Monomer	B cell receptor	B cell surface

Summary Table: Types of Hypersensitivity

Type	Immune Component	Onset	Example
Immediate	IgE	Seconds	Allergy, anaphylaxis
Subacute	IgM, IgG	1–3 hours	Mismatched blood transfusion
Delayed	T cells	1–3 days	Contact dermatitis, TB skin test