Review of Medical Microbiology and Immunology (Medical Microbiology & Immunology

1. The Immune System: A Multi-Layered Defense

The main function of the immune system is to prevent or limit infections by microorganisms such as bacteria, viruses, fungi, and parasites.

Defense in Depth. The immune system is not a single entity but a complex network of cells, tissues, and proteins working together to protect the body from harmful invaders. It operates on multiple levels, from physical barriers to highly specialized cellular responses, ensuring comprehensive protection.

Three Lines of Defense:

• First Line: Physical barriers like skin and mucous membranes prevent entry.
• Second Line: Innate immunity provides immediate, non-specific responses.
• Third Line: Adaptive immunity offers specific, long-lasting protection.

Interconnectedness: These layers are not independent; they interact and influence each other. For example, innate responses activate adaptive immunity, and adaptive responses enhance innate mechanisms. This interplay ensures a coordinated and effective defense against a wide range of threats.

2. Innate Immunity: The Body's First Responders

Because the components of the innate arm (Table 57–1) are preformed and fully active, they can function immediately upon entry of the microorganisms.

Immediate Action. Innate immunity is the body's rapid response system, ready to act within minutes of an invasion. It doesn't require prior exposure to a pathogen and provides a broad, non-specific defense.

Key Components:

• Physical Barriers: Skin, mucous membranes, and secretions like tears and saliva.
• Cellular Defenders: Macrophages, neutrophils, and natural killer (NK) cells.
• Proteins: Complement, interferons, and defensins.
• Processes: Phagocytosis, inflammation, and fever.

Pattern Recognition: Innate immune cells recognize foreign invaders through pattern-recognition receptors that detect molecules common to many microbes but absent in human cells. This allows for a quick response without needing specific recognition of each pathogen. For example, Toll-like receptors (TLRs) recognize endotoxins from gram-negative bacteria and mannan-binding lectin (MBL) binds to mannan on the surface of bacteria and yeasts.

3. Adaptive Immunity: Specific and Long-Lasting Protection

Highly specific protection is provided by the acquired (adaptive) arm of the immune system (third line of defense), but it takes several days for this arm to become fully functional.

Targeted Defense. Adaptive immunity provides highly specific protection against pathogens, targeting them with precision. It develops over time and improves with repeated exposure, offering long-lasting immunity.

Two Main Branches:

• Humoral Immunity: Antibody-mediated, primarily effective against extracellular pathogens.
• Cell-Mediated Immunity: T-cell-mediated, primarily effective against intracellular pathogens.

Key Features:

• Specificity: Recognizes and targets specific antigens.
• Memory: Remembers past encounters and responds more rapidly upon re-exposure.
• Diversity: Can respond to millions of different antigens.

Adaptive immunity is essential for long-term protection and is the basis for vaccines, which induce memory responses to specific pathogens.

4. T Cells: Orchestrators of Cellular Immunity

The cell-mediated arm consists primarily of T lymphocytes (e.g., helper T cells and cytotoxic T cells), whereas the antibody-mediated arm consists of antibodies (immunoglobulins) and B lymphocytes (and plasma cells).

Cellular Commanders. T cells are lymphocytes that play a central role in cell-mediated immunity, orchestrating immune responses and directly attacking infected cells. They mature in the thymus and are characterized by their T-cell receptors (TCRs).

Two Main Types:

• Helper T Cells (CD4+): Activate other immune cells, including B cells and cytotoxic T cells, by producing cytokines.
• Cytotoxic T Cells (CD8+): Directly kill virus-infected cells, tumor cells, and allografts.

Activation Process: T cells are activated when their TCRs recognize antigens presented by antigen-presenting cells (APCs) in association with MHC proteins. This interaction requires costimulatory signals for full activation. T cells are essential for controlling intracellular infections and tumors.

5. B Cells: Antibody Production Powerhouses

Antibody synthesis typically involves the cooperation of three cells: macrophages, helper T cells, and B cells.

Antibody Factories. B cells are lymphocytes responsible for producing antibodies, which are crucial for humoral immunity. They mature in the bone marrow and express surface immunoglobulins (IgM and IgD) that act as antigen receptors.

Activation and Differentiation: B cells are activated when their surface immunoglobulins bind to antigens. This activation, often aided by helper T cells, leads to proliferation and differentiation into plasma cells, which secrete large amounts of antibodies.

Key Functions:

• Antibody Production: Neutralize toxins and viruses, opsonize bacteria, and activate complement.
• Antigen Presentation: Present antigens to helper T cells.
• Memory Cell Formation: Provide long-term protection.

B cells are essential for defense against extracellular pathogens and toxins.

6. Antigens: The Triggers of Immune Responses

Antigens are molecules that react with antibodies, whereas immunogens are molecules that induce an immune response.

Immune System Targets. Antigens are molecules that can be recognized by the immune system, triggering an immune response. They can be proteins, polysaccharides, lipids, or nucleic acids.

Immunogenicity vs. Antigenicity:

• Immunogens: Molecules that induce an immune response.
• Antigens: Molecules that react with antibodies or T-cell receptors.
• Most immunogens are also antigens, but some antigens (haptens) are not immunogenic on their own.

Epitopes: Antigens have specific regions called epitopes that are recognized by antibodies or T-cell receptors. The size and complexity of an antigen, as well as its foreignness, determine its immunogenicity. Adjuvants enhance the immune response to an immunogen.

7. The Major Histocompatibility Complex (MHC): Self vs. Non-Self

The genes for the HLA proteins are clustered in the major histocompatibility complex (MHC), located on the short arm of chromosome 6.

Self-Recognition System. The MHC is a cluster of genes that encode proteins on cell surfaces that play a crucial role in distinguishing self from non-self. These proteins, also known as human leukocyte antigens (HLA), are highly polymorphic, meaning they vary greatly among individuals.

Two Main Classes:

• Class I MHC: Found on all nucleated cells, present antigens to cytotoxic T cells (CD8+).
• Class II MHC: Found on antigen-presenting cells, present antigens to helper T cells (CD4+).

Transplantation and Disease: MHC proteins are critical in transplant rejection and are associated with susceptibility to certain autoimmune diseases. The MHC proteins are essential for T-cell activation and immune responses.

8. Complement: Amplifying the Immune Response

The complement system consists of approximately 20 proteins that are present in normal human (and other animal) serum.

Immune System Amplifier. The complement system is a group of serum proteins that enhance the immune response. It can be activated by antigen-antibody complexes or by microbial surfaces, leading to a cascade of reactions.

Three Activation Pathways:

• Classic Pathway: Activated by antigen-antibody complexes.
• Lectin Pathway: Activated by mannan-binding lectin (MBL) binding to microbial surfaces.
• Alternative Pathway: Activated by microbial surfaces directly.

Key Functions:

• Cell Lysis: Forms the membrane attack complex (MAC) that kills cells.
• Opsonization: Coats microbes, making them easier to phagocytize.
• Inflammation: Generates mediators that attract immune cells and promote inflammation.

Complement is a crucial component of both innate and adaptive immunity.

9. Hypersensitivity: When the Immune System Overreacts

Hypersensitivity is the term used when an immune response results in exaggerated or inappropriate reactions harmful to the host.

Immune System Gone Wrong. Hypersensitivity reactions occur when the immune system responds excessively or inappropriately to an antigen, causing tissue damage and disease.

Four Main Types:

• Type I (Immediate): IgE-mediated, causing anaphylaxis, allergies, and asthma.
• Type II (Cytotoxic): Antibody-mediated, causing cell lysis, e.g., transfusion reactions.
• Type III (Immune Complex): Antibody-mediated, causing inflammation, e.g., serum sickness.
• Type IV (Delayed): T-cell-mediated, causing delayed inflammation, e.g., contact dermatitis.

Understanding hypersensitivity reactions is crucial for diagnosing and managing allergic and autoimmune diseases.

10. Tolerance and Autoimmunity: Maintaining Balance and When It Fails

In general, molecules recognized as "self" are not immunogenic; i.e., we are tolerant to those self-molecules.

Self-Recognition and Balance. Tolerance is the ability of the immune system to recognize and not react to self-antigens. Autoimmunity occurs when this tolerance is lost, and the immune system attacks the body's own tissues.

Mechanisms of Tolerance:

• Clonal Deletion: Elimination of self-reactive T cells in the thymus.
• Clonal Anergy: Inactivation of self-reactive T cells in the periphery.
• Regulatory T Cells: Suppress immune responses.

Autoimmune Diseases: Result from a breakdown in tolerance, leading to chronic inflammation and tissue damage. They can be caused by genetic predisposition, environmental triggers, and molecular mimicry. Examples include rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes.

Last updated: January 15, 2025