Overview of the Immune System

Innate vs. Adaptive Immunity

The immune system is divided into two main branches: innate immunity and adaptive immunity. Each plays a distinct role in defending the body against pathogens.

• Innate Immunity: Present at birth, non-specific, rapid response (minutes to hours), no memory, same response each time.

• Adaptive Immunity: Develops after exposure, specific to pathogens, slower response (days), has memory, stronger with repeat exposure.

Role of Normal Microbiota

Functions of Normal Microbiota

Normal microbiota are beneficial microorganisms that inhabit the human body and contribute to immune defense.

• Compete with pathogens for nutrients and space.

• Produce antimicrobial substances.

• Stimulate immune responses.

First-Line Defenses (Barriers)

Physical, Mechanical, and Chemical Barriers

First-line defenses prevent pathogen entry through various barriers:

• Physical Barriers: Skin, mucous membranes.

• Mechanical Barriers: Mucus trapping microbes, cilia movement, tears, and saliva flushing microbes.

• Chemical Barriers: Lysozyme (in tears, saliva, sweat), antimicrobial peptides, stomach acid (low pH).

Second-Line Defenses

Cellular and Molecular Defenses

When pathogens bypass first-line defenses, the body employs cellular and molecular mechanisms to eliminate them.

• Cellular Defenses: Involve various white blood cells (leukocytes).

• Molecular Defenses: Include cytokines, iron-binding proteins, and the complement system.

Lymphatic System

Structure and Function

The lymphatic system filters pathogens and supports immune cell development.

• Lymph: Fluid collected from tissues, filtered through lymph nodes.

• Primary Lymphoid Tissues: Bone marrow, thymus (sites of immune cell development).

• Secondary Lymphoid Tissues: Lymph nodes, spleen, tonsils (sites of immune response initiation).

Leukocytes (White Blood Cells)

Types and Functions

Leukocytes are divided into granulocytes and agranulocytes, each with specialized roles.

Note: Overproduction or underproduction of these cells can lead to immune disorders (e.g., leukocytosis, leukopenia).

Molecular Second-Line Defenses

Cytokines, Iron-Binding Proteins, and Complement System

• Cytokines: Cell signaling proteins (e.g., interleukins, interferons) that coordinate immune responses.

• Iron-Binding Proteins: (e.g., transferrin, lactoferrin) limit bacterial growth by sequestering iron.

• Complement System: A cascade of proteins activated via classical, alternative, or lectin pathways, leading to opsonization, inflammation, and cell lysis.

Inflammation

Phases and Signs

Inflammation is a protective response to infection or injury, but chronic inflammation can cause tissue damage.

• Phases: Vascular changes, leukocyte recruitment, resolution.

• Cardinal Signs: Redness, heat, swelling, pain.

• Chemical Mediators: Histamine, cytokines, prostaglandins.

Chronic inflammation can lead to diseases such as arthritis.

Fever

Mechanism and Benefits

Fever is an elevated body temperature in response to infection, mediated by pyrogens that reset the hypothalamus.

• Slows pathogen growth

• Enhances immune response

• Types: Low-grade, intermittent, remittent, sustained

• Managed with antipyretics, fluids, and treating the underlying cause

Cancer and the Immune System

Immune Surveillance and Failure

The immune system detects and eliminates abnormal cells. Cancer develops when immune surveillance fails, allowing cancer cells to evade detection and suppress immune responses.

Hygiene Hypothesis

Microbiota and Immune Development

The hygiene hypothesis suggests that reduced exposure to diverse microbes may negatively affect immune responses, potentially increasing susceptibility to allergies and autoimmune diseases.

Immunodeficiencies & HIV (Chapter 13)

Immunodeficiency Overview

Immunodeficiency is the lack of a properly functioning immune system, leading to increased susceptibility to infections.

• Primary Immunodeficiency: Congenital, present at birth, affects one or more immune components, rare but serious (e.g., DiGeorge Syndrome).

• Secondary Immunodeficiency: Acquired, develops over time due to infection (e.g., HIV), disease, or environmental factors.

Autoimmunity

Autoimmunity occurs when the immune system attacks self tissues, resulting in chronic autoimmune disorders.

• Examples: Rheumatoid arthritis, multiple sclerosis, Graves’ disease, celiac disease, lupus, type 1 diabetes.

• Types: Systemic (multiple tissues) or localized (one tissue type).

• Symptoms: Joint/muscle pain, fatigue, rash, organ dysfunction, low-grade fever.

Hypersensitivity

Hypersensitivity is an inappropriate immune response, such as allergies or autoimmune reactions, which can be localized or systemic.

HIV and AIDS

HIV is a retrovirus that targets the immune system, leading to acquired immunodeficiency syndrome (AIDS) if untreated.

• Structure: Enveloped RNA virus with reverse transcriptase, integrase, and protease.

• Attachment: gp120 binds CD4 receptor; gp41 promotes fusion; co-receptors (CCR5 or CXCR4) facilitate entry.

• Target Cells: Helper T cells (CD4+), macrophages, dendritic cells.

HIV Replication Cycle

1. Attachment (CD4 + gp120)

2. Fusion (gp41)

3. Reverse transcription (ssRNA to dsDNA by reverse transcriptase)

4. Integration into host genome (integrase)

5. Replication of viral genome and proteins

6. Assembly

7. Release (budding; protease matures virion)

Opportunistic Infections (OIs) and AIDS-Defining Illnesses

• OIs occur when the immune system is weakened (e.g., in HIV patients).

• AIDS-defining illnesses indicate progression to AIDS (e.g., Pneumocystis pneumonia, Kaposi’s sarcoma).

Antimicrobial Drugs (Chapter 15)

Mechanisms of Action

Antimicrobial drugs target specific structures or processes in microbes. Understanding their mechanisms is essential for effective use and combating resistance.

Protein Synthesis Inhibitors

These drugs target bacterial ribosomes (30S or 50S subunits), exploiting differences from eukaryotic ribosomes for selective toxicity.

Antifungal, Antiviral, and Antiparasitic Drugs

Mechanisms of Antibiotic Resistance

Bactericidal vs. Bacteriostatic

High-Yield Drug Toxicities

Exam Tips

• Know differences between innate and adaptive immunity, including key cells and barriers.

• Understand the complement cascade, inflammation steps, and cardinal signs.

• Be able to explain the HIV lifecycle and recognize AIDS-defining illnesses.

• Prioritize understanding mechanisms of antimicrobial drugs, resistance, and toxicities.

Additional info: For more details on specific tables and figures, refer to your textbook or previous study guides as indicated in the notes.