Innate and Adaptive Immunity, Immunodeficiencies, HIV, and Antimicrobial Drugs: Study Notes

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.

Feature	Innate Immunity	Adaptive Immunity
Response Time	Immediate	4–7 days
Organisms	All eukaryotes	Only vertebrates
Distinguishes Self/Foreign	Yes	Yes
Kills Invaders	Yes	Yes
Effective Against Diverse Threats	Yes	Yes
Tailors Response to Antigen	No	Yes
Memory	No	Yes

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.

Cell Type	Function
Neutrophils	First responders, phagocytosis, rapid bacterial killing
Eosinophils	Fight parasites, involved in allergies
Basophils & Mast Cells	Release histamine, trigger inflammation
Monocytes → Macrophages	Phagocytosis, antigen presentation
Dendritic Cells	Bridge innate and adaptive immunity
Lymphocytes (B cells, T cells, NK cells)	Antibody production, killing infected cells, immune regulation

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.

Molecular Defense	Function(s)
Cytokines	Stimulate inflammation, generate fever, recruit leukocytes, tissue repair, immune regulation
Iron-Binding Proteins	Limit iron availability to bacteria
Complement Proteins	Stimulate inflammation, opsonization, cytolysis

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)

HIV	AIDS
Virus infection	Advanced disease stage
May be asymptomatic	Severe immune damage
Treatable	Life-threatening

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.

Target	Drug Family	Examples	Notes
Cell wall synthesis	Penicillins	Penicillin V, G, Ampicillin	Narrow to broad spectrum; end in -cillin
Cell wall synthesis	Cephalosporins	Cephalexin, Cefapirin, Ceftaroline	Start with cef-/ceph-
Cell wall synthesis	Carbapenems	Doripenem, Imipenem, Meropenem	Last-line drugs
Cell wall synthesis	Monobactams	Aztreonam	Gram-negative only
Cell wall synthesis	Glycopeptides	Vancomycin	Red man syndrome
DNA replication	Fluoroquinolones	Ciprofloxacin, Levofloxacin	Tendon rupture risk

Protein Synthesis Inhibitors

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

Target	Drug Class	Examples	Key Side Effects
30S ribosome	Aminoglycosides	Gentamicin, Streptomycin	Hearing loss, kidney damage
30S ribosome	Tetracyclines	Doxycycline	Tooth discoloration
50S ribosome	Macrolides	Azithromycin, Erythromycin	GI upset
50S ribosome	Lincosamides	Clindamycin	C. difficile infection
50S ribosome	Phenicols	Chloramphenicol	Bone marrow suppression

Antifungal, Antiviral, and Antiparasitic Drugs

Target	Drug Class	Examples	Mechanism
Fungal cell membrane	Polyenes	Nystatin, Amphotericin B	Bind ergosterol
Fungal cell membrane	Azoles	Fluconazole	Inhibit ergosterol synthesis
Fungal cell wall	Echinocandins	Caspofungin	Inhibit beta-glucan synthesis
RNA virus	Remdesivir	COVID-19	Inhibits viral replication
HIV	HAART	Multiple drugs	Blocks viral lifecycle
Herpes viruses	Acyclovir	HSV	Inhibits DNA synthesis
Influenza	Oseltamivir	Flu	Blocks viral release
Malaria	Aminoquinolines	Chloroquine, Hydroxychloroquine	Resistance increasing
Malaria	Artemisinins	Artesunate	Most effective; ACT therapy

Mechanisms of Antibiotic Resistance

Mechanism	Description	Example
Drug inactivation	Enzyme destroys drug	Beta-lactamase
Target modification	Drug binding site altered	MRSA

Bactericidal vs. Bacteriostatic

Type	Definition	Examples	Clinical Use
Bactericidal	Kills bacteria	Penicillin, Vancomycin	Severe infections
Bacteriostatic	Stops growth	Tetracycline, Macrolides	Mild infections

High-Yield Drug Toxicities

Drug Class	Toxicity	Key Symptom
Aminoglycosides	Nephrotoxicity	Kidney damage
Aminoglycosides	Ototoxicity	Hearing loss
Fluoroquinolones	Tendon rupture	Achilles pain
Vancomycin	Red man syndrome	Flushing
Tetracyclines	Tooth discoloration	Yellow teeth
Chloramphenicol	Bone marrow suppression	Anemia
Amphotericin B	Kidney toxicity	Renal failure

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.