Introduction to Immunology: Innate and Adaptive Host Defenses

I. Fundamentals of Host Defense

Basic Properties of the Immune System

The immune system protects organisms from infection through a complex network of cells, tissues, and molecules. Immunity is the ability to resist infection and is divided into innate and adaptive branches.

• Immunity: The ability of an organism to resist infection.

• Innate immunity (nonspecific immunity):

  • Noninducible ability to recognize and destroy an individual pathogen or its products.

  • Does not require previous exposure to a pathogen or its products.

  • Provides immediate, broad-spectrum defense.

• Adaptive immunity:

  • Acquired ability to recognize and destroy a particular pathogen or its products.

  • Dependent on previous exposure (specificity).

  • Directed toward individual molecular components of the pathogen (antigen).

Barriers to Pathogen Invasion

• Natural Host Resistance: Normal microbiota help resist pathogens, especially on the skin and in the gut, through competitive exclusion.

• Physical and Chemical Barriers:

  • Mucosal membranes coated with mucus trap pathogens.

  • Stomach acid inhibits bacterial growth.

  • Skin is salty and acidic, limiting bacterial growth.

II. Cells and Organs of the Immune System

The Blood and Lymphatic Systems

The immune system relies on specialized cells and organs distributed throughout the body.

• Lymphatic system: Separate circulatory system that drains lymph fluid from extravascular tissues.

• Blood: Circulates cells and solutes; leukocytes and solutes pass from blood into the lymphatic system at capillary beds.

• Lymph nodes: Contain high concentrations of lymphocytes and phagocytes.

• Leukocytes: Nucleated white blood cells (0.1% of blood cells), including phagocytes and lymphocytes.

Leukocyte Production and Diversity

• Lymphocytes: Specialized leukocytes involved in adaptive immunity.

• Two main types:

  • B cells: Originate and mature in bone marrow.

  • T cells: Originate in bone marrow, mature in thymus.

• Primary lymphoid organs: Bone marrow and thymus.

III. Phagocyte Response Mechanisms

Pathogen Challenge and Phagocyte Recruitment

• Tissue damage triggers recruitment of phagocytes.

• Chemokine release: Resident leukocytes and damaged cells release cytokines and chemokines, attracting macrophages and neutrophils (extravasation).

Pathogen Recognition and Phagocyte Signal Transduction

• Pathogen-associated molecular patterns (PAMPs): Structures and molecules unique to pathogens (e.g., peptidoglycan, flagellin, dsRNA).

• Pattern recognition receptors (PRRs): Leukocyte proteins (membrane-bound or soluble) that recognize PAMPs.

Phagocytosis and Phagocyte Inhibition

• Some pathogens survive phagolysosome destruction:

  • Mycobacterium tuberculosis produces carotenoids to neutralize singlet oxygen and has a waxy cell wall to absorb free radicals, allowing survival and division within phagocytes.

  • Streptococcus pyogenes produces leukocidins that kill white blood cells (pus formation).

  • Capsule-forming pathogens (e.g., Streptococcus pneumoniae) resist phagocytosis; host antibodies can counteract this (basis for pneumococcal vaccines).

IV. Other Innate Host Defenses

Inflammation and Fever

• Inflammation: Nonspecific reaction to harmful stimuli, characterized by redness, swelling, pain, and heat at the infection site.

• Cytokines and chemokines draw white blood cells to the site, isolating and limiting tissue damage.

• Excessive inflammation can damage healthy tissue, especially in vital organs.

Fever

• Certain cytokines (e.g., IL-1) act as pyrogens, raising body temperature.

• Fever increases circulation rate, enhancing leukocyte delivery to infection sites.

• Some pathogens cannot tolerate elevated temperatures.

• Fever increases transferrins, which sequester iron and limit pathogen growth.

Systemic Inflammation and Septic Shock

• Systemic inflammation increases vascular permeability, lowering blood pressure and risking multi-organ damage (shock).

• Gram-negative bacteria (with LPS) can trigger a fatal cytokine storm.

V. Principles of Adaptive Immunity

Specificity, Memory, Selection Processes, and Tolerance

• Specificity: Antigen-antibody reactions depend on lymphocyte receptors interacting with individual antigens.

• Memory: Subsequent exposures to the same antigen result in rapid, robust responses due to memory T and B cells.

  • Primary response: Initial exposure induces multiplication of antigen-reactive cells (clones).

  • Secondary response: Faster and stronger due to memory cells.

Immunogens and Classes of Immunity

• Antibodies bind to specific regions of antigens called epitopes or antigenic determinants (may be sugars, amino acids, or other molecules).

Classes of Adaptive Immunity

• Active immunity: Generated by exposure to antigen; develops memory cells and long-lasting immunity.

• Passive immunity: Transfer of pre-formed antibodies or cells; rapid but short-lived protection.

Active Immunity	Passive Immunity
Exposure to antigen; immunity achieved by purposely administering antigen or through infection	No exposure to antigen; immunity achieved by injecting antibodies or antigen-reactive T cells
Specific immune response made by individual achieving immunity	Specific immune response made by donor of antibodies or T cells
Immunity activated by antigen; immune memory in effect	No immune system activation; no immune memory
Immunity can be maintained via stimulation of memory cells (e.g., booster immunization)	Immunity cannot be maintained and decays rapidly
Immunity develops over a period of weeks	Immunity develops immediately

Natural and Artificial Immunity

• Natural immunity: Occurs without medical intervention.

  • Natural active: Getting a disease and recovering.

  • Natural passive: Passing antibodies to infants via breast milk.

• Artificial immunity: Requires injections or infusions.

  • Artificial active: Receiving a vaccination and developing immunity.

  • Artificial passive: Receiving pre-formed antibodies (antiserum).

VI. Antibodies

B Cells, Antibodies, and Memory

• B cells have ~100,000 identical B cell receptors (BCRs) per cell, which bind and internalize antigen.

• With T cell help, B cells proliferate and differentiate into:

  • Plasma cells: Produce antibodies.

  • Memory cells: Provide long-term protection.

VII. Immune Disorders and Deficiencies

Allergy, Hypersensitivity, and Autoimmunity

• Hypersensitivity: Inappropriate immune response causing host damage.

• Classified by antigens and effector mechanisms.

• Allergy: Antibody-mediated immediate hypersensitivity.

Autoimmunity

• Occurs when T and B cells react against self proteins, causing tissue damage.

• Some diseases are caused by autoantibodies (antibodies against self antigens).

Disease	Organ/Tissue Affected	Mechanism (Autoimmunity Basis)
Type I diabetes (insulin-dependent)	Pancreas	Cell-mediated immunity and autoantibodies against surface and cytoplasmic antigens of beta cells
Myasthenia gravis	Skeletal muscle	Autoantibodies against acetylcholine receptor on muscle
Rheumatoid arthritis	Cartilage	Autoantibodies against IgG antibodies, which deposit in joints
Multiple sclerosis	Brain	Cell-mediated immunity and autoantibodies against antigens in myelin sheath

Immunodeficiency

• Active adaptive immunity is critical for resistance to infectious disease.

• Deficiencies in B cells: Prone to bacterial infections.

• Deficiencies in T cells: Prone to viral infections and cancers.

• Severe combined immune deficiency syndrome (SCID): Congenital deficiency of both B and T cells; patients require isolation from pathogens.

• Acquired Immunodeficiency Syndrome (AIDS): Caused by HIV, which kills CD4+ T cells, leading to susceptibility to opportunistic infections and cancer.