Chapter 12: White Blood Cells and Immunity

White Blood Cells (WBCs) and Immunity

Three Major Categories of WBCs

  • Monocytes:

    • Mature into macrophages.

    • Categorized as an agranulocyte (lacks granules in cytoplasm).

  • Lymphocytes:

    • Include T and B cells.

    • Categorized as an agranulocyte.

  • Granulocytes:

    • Include Basophils, Eosinophils, and Neutrophils.

Overview of WBCs (Leukocytes)

  • Function: Protect against infection.

  • Production: Produced in the bone marrow, which also produces RBCs and platelets.

  • Innate Immunity (First Line of Defense):

    • Nonspecific and immediate defense.

    • Components: Neutrophils, macrophages.

    • Involves the inflammatory response.

  • Adaptive Immunity (Specific and Acquired):

    • Specific response to pathogens.

    • Components: B and T lymphocytes.

    • Develops memory cells for quicker future responses.

Types of White Blood Cells

  • Monocytes

  • Macrophages (mature monocytes)

  • Eosinophils

  • Lymphocytes

  • Neutrophils (polymorphonuclear leukocytes, PMNs)

  • Basophils

Granulocytes: Detailed Breakdown

  • Cytoplasm contains granules of chemicals.

  • Eosinophils:

    • Constitute 1 to 7\% of circulating WBCs.

    • Elevate during parasitic infections and allergies.

  • Basophils:

    • Constitute <2\% of circulating WBCs.

    • Elevate during infection and inflammation.

    • Contain histamine, a potent vasodilator and inflammatory mediator.

  • Neutrophils:

    • Most common granulocyte, making up 40 to 80\% of circulating WBCs.

    • First responders to infection and inflammation.

    • Carry out phagocytosis (engulfing and destroying microorganisms).

    • Release enzymes to destroy microorganisms.

    • Form free radicals (respiratory burst) to destroy microbes.

    • Also known as Polymorphonuclear (PMN) cells due to their multi-lobed nuclei.

    • Mature neutrophils: Known as “Segs” (segmented nuclei).

    • Immature neutrophils: Known as “Bands” (band-like or C-shaped nuclei).

    • “Shift to the left”: A high number of bands, indicating an increased formation of immature neutrophils in response to acute infection.

Synthesis and Maturation of WBCs

  • Pluripotent stem cells in bone marrow give rise to all blood cells (WBCs, RBCs, platelets).

  • Myeloid stem cells:

    • Differentiate into granulocytes and monocytes.

  • Lymphoid stem cells:

    • Differentiate into T and B cells.

    • B cells: Antibody-producing cells.

    • T cells: Include CD4 (helper T cells) and CD8 (cytotoxic T cells) cells.

  • “Blast cells”: Immature, precursor cells.

White Blood Cell Response Chronology

  • First 6-24 hours: Neutrophils are the dominant responders.

  • 24-48 hours: Neutrophils are gradually replaced by monocytes, which mature into macrophages.

  • Persistent inflammation: Macrophages predominate and continue phagocytosis.

  • Viral infections: Lymphocytes dominate the immune response.

Macrophage and Phagocytosis

  • Macrophages can move out of capillaries (via capillary pores) to reach sites of infection.

  • They engulf and capture antigens (e.g., bacteria).

  • Lysosomes within the macrophage contain enzymes used to digest the antigen.

Immunity: General Principles

  • The body's immune system constantly defends against microbes.

  • It is self-regulated and self-limiting.

  • Must be able to distinguish self from nonself through recognition of antigens.

  • Two key activities: Defense against and attack of foreign invaders.

Neutrophils: Key Properties

  • Lifespan: Short, hours to days.

  • Role: Acute responder in inflammation.

  • Mechanism: Phagocytosis and respiratory burst (releases free radicals to destroy microbes).

  • Nomenclature: Also known as PMNs (polymorphonuclear cells).

  • Maturation: Mature neutrophils have segmented nuclei; immature neutrophils are called “bands.”

  • Clinical sign: Acute infection leads to a “shift to the left,” where more bands are produced than segs.

Alterations in WBC Numbers

  • Neutropenia:

    • Defined as <1,500 neutrophils/microliter.

    • Compromises the immune response, increasing infection risk.

    • Causes: Various factors, including certain medications like chemotherapy.

    • Treatment: Filgrastim (Neupogen) stimulates neutrophil synthesis.

Human Immunodeficiency Virus (HIV)

HIV: Transmission Routes

  • Sexual activity (semen and vaginal secretions).

  • Blood (transfusions, sharing needles).

  • Transplacental (mother to fetus during pregnancy).

  • Breast milk.

  • Organ transplants.

  • Saliva (when it enters open mouth wounds).

  • High-risk individuals: Those participating in unsafe sex, men who have sex with men (MSM), and intravenous (IV) drug abusers.

HIV: Virology and Mechanism

  • Types: HIV-1 (more common in US) and HIV-2 (more common in West Africa).

  • Classification: Retrovirus (RNA virus).

  • Key enzyme: Reverse transcriptase converts HIV RNA into DNA.

  • Target cells: Cells that express CD4 receptors, primarily CD4 helper T cells, but also macrophages.

  • Dormancy: Can remain dormant in inactive CD4 cells.

  • Reservoir: Macrophages can serve as a reservoir for HIV.

  • Immune compromise: Infected CD4 cells are unable to carry out normal functions, severely compromising adaptive immunity.

  • Progression: HIV eventually destroys CD4 cells, leading to an increased risk of opportunistic infections.

HIV: Complications and Progression

  • Opportunistic infections: Examples include Pneumocystis pneumonia and tuberculosis.

  • Malignancies: Examples include Kaposi sarcoma and non-Hodgkin's lymphoma.

  • Progression to AIDS (Acquired Immune Deficiency Syndrome).

  • Asymptomatic phase: Virus reproduces for several years without overt symptoms.

  • Symptomatic phase: As viral load rises and CD4 count drops, symptoms increase in severity.

  • Three potential forms of progression: Immunodeficiency, autoimmunity, and neurologic dysfunction.

AIDS (Acquired Immune Deficiency Syndrome)

  • No cure, but effective management is achieved with combination therapy.

  • Highly Active Antiretroviral Therapy (HAART):

    • Regimens may need to change due to viral adaptation.

    • Other medicines and vaccines prevent opportunistic infections.

  • Transmission prevention methods:

    • Pre-exposure prophylaxis (PrEP) medications.

    • Post-exposure prophylaxis (PEP) medications.

    • Avoiding contact with bodily fluids.

    • Education.

    • Consistent use of condoms.

    • Male circumcision (reduces risk of female-to-male transmission of STIs).

Inflammation

Inflammation Overview

  • Coordinated response to injury or infection.

  • Goals: Wall off injured area, prevent spread of injury, and bring body’s defenses to the needed area.

  • Process: Multi-stage.

  • Classification: Can be local or systemic, acute or chronic.

Acute Inflammation

  • Characteristics: Rapid onset, terminates quickly.

  • Mechanism: Chemical mediators orchestrate the response.

  • Three phases:

    1. Increased vascular permeability.

    2. Cellular chemotaxis.

    3. Systemic response.

Phase 1: Increased Vascular Permeability

  • Chemical mediators: Histamine and bradykinin dilate vessels.

  • Fluid movement: Fluid, WBCs, and platelets travel to the injury site.

  • Benefits: Toxins are diluted, WBCs phagocytize foreign matter and debris.

  • Five Classic Signs of Inflammation:

    1. Rubor (redness): Due to vasodilation and increased blood flow.

    2. Tumor (swelling): Due to fluid extravasation into tissues.

    3. Calor (heat): Due to increased blood flow.

    4. Dolor (pain): Due to pressure from swelling and chemical mediators.

    5. Loss of function (function laesa): Due to swelling and pain.

  • Exudates (fluid released during inflammation):

    • Purulent exudate (pus): Contains proteins, microbes, and cell debris; appears as white-green discharge.

    • Transudate: Watery, clear fluid (e.g., non-infected blister).

  • Complications of fluid accumulation:

    • Abscess: Localized, walled-off collection of purulent exudate.

    • Effusion: Accumulation of fluid in a body cavity.

Phase 2: Cellular Chemotaxis

  • Chemotaxis: Chemical signals released by WBCs, endothelial cells, and microbial agents attract WBCs and platelets to the injury site.

  • Margination: WBCs line up along the endothelium (inner lining of blood vessels).

  • Inflammatory mediators: WBCs release these to further promote the inflammatory response.

Inflammatory Mediators

  • Promote or inhibit inflammation; many pharmacological agents modulate these.

  • Cytokines: Released by WBCs; examples include Tumor Necrosis Factor (TNF)-alpha and Interleukins (ILs).

  • Chemokines: Proteins that attract leukocytes to the endothelium.

Acute Phase Proteins

  • Produced by the liver in response to cytokines.

  • C-reactive protein (CRP):

    • Marks foreign material for phagocytosis.

    • Activates the complement system.

    • Stimulates other inflammatory cytokines.

    • Elevation indicates active inflammation.

    • High sensitivity CRP is a marker for increased risk of myocardial infarction.

  • Fibrinogen:

    • Binds to red blood cells, causing them to stack and precipitate (rouleaux and sedimentation).

    • Elevated Erythrocyte Sedimentation Rate (ESR) indicates active inflammation.

Phase 3: Systemic Responses in Acute Inflammation

  • Symptoms: Fever, lymphadenopathy (enlarged lymph nodes), anorexia, sleepiness, lethargy, anemia, weight loss.

  • Cause: Most signs are due to chemical mediators like pyrogens, TNF-alpha, and interleukins.

  • Treatment: Drugs to reduce inflammation target these signals.

Fever

  • Mechanism: Pyrogens (released by WBCs and microorganisms) cause prostaglandins to reset the body's temperature set point in the hypothalamus.

  • Benefit: Higher temperatures increase WBC efficiency.

  • Treatment: Anti-prostaglandins (e.g., NSAIDs) reduce fever.

  • Reye’s syndrome: Never give children or adolescents aspirin to reduce fever due to the risk.

  • Progression: Fever onset involves shivering to increase temperature; fever “breaks” with sweating to reduce temperature.

Lymphadenopathy

  • Definition: Enlargement of lymph nodes, often due to an inflammatory process.

  • Function: Lymphocytes (B and T cells) mature in lymph nodes.

  • Significance: Lymphatic fluid circulates throughout the body; injurious agents in the lymph system can invade other tissues.

Key Inflammatory Mediators

  • Histamine:

    • Produced by basophils, platelets, and mast cells.

    • Systemic effects: Arteriolar vasodilation, large artery vasoconstriction, increased permeability of venules.

    • Example: Sneezing, runny nose, pharyngeal irritation in upper respiratory tract allergies.

  • Prostaglandins (PGs) and Leukotrienes:

    • Synthesis: Phospholipase breaks down phospholipids to form arachidonic acid (AA).

    • AA is then converted to PGs and leukotrienes.

    • Cyclooxygenase-1 (COX-1): Produces “helpful” PGs, such as those that stimulate mucus production to protect gastric mucosa.

    • Cyclooxygenase-2 (COX-2): Produces “inflammatory” PGs, causing pain, fever, and swelling.

    • Lipoxygenase: Forms leukotrienes, which cause bronchiole contraction in asthma.

  • TNF-alpha and Interleukins (ILs):

    • Production: Inflammatory signals primarily produced by macrophages.

    • Effects: Induce fever, loss of appetite, and lethargy.

    • TNF-alpha specifically promotes weight loss and cachexia.

    • TNF-alpha increases endogenous corticosteroids.

Acute vs. Chronic Inflammation

Feature

Acute Inflammation

Chronic Inflammation

Onset/Duration

Rapid onset, terminates quickly

Weeks to months without resolution or healing

Primary Cells

Neutrophils

Predominance of monocytes, lymphocytes, and macrophages

Causes

Chemical irritants, infection, allergic reactions, trauma (burns, lacerations)

Persistent infection (tuberculosis, syphilis), hypersensitivity disorders (RA, SLE), toxic agents (coal dust), atherosclerosis, some cancers

Tissue Damage/Repair

Limited, aims to heal quickly

Continual secretion of cytokines damages healthy tissues, stimulating further inflammation; granuloma formation may occur

Chronic Inflammation Detailed

  • Granuloma formation: Macrophages aggregate and are transformed into epithelial-like cells; T and B lymphocytes amplify and perpetuate inflammatory signals.

  • Autoimmune disorders: Often characterized by chronic inflammation.

Wound Healing

Four Phases of Wound Healing

  1. Hemostasis: Initial phase involving vasoconstriction and clot formation.

  2. Inflammation: (Described previously) Response to injury.

  3. Proliferation, Granulation Tissue Formation, Angiogenesis, Epithelialization: New tissue forms, blood vessels grow, and the wound surface is covered.

  4. Wound Contraction and Remodeling: The wound shrinks, and the collagen fibers strengthen and reorganize.

Eschar and Debridement

  • Eschar: Dead tissue that sheds or falls off from healthy skin; typically tan, brown, or black with a crusty top.

  • Debridement: Surgical or enzymatic removal of necrotic tissue; promotes re-epithelialization.

Factors That Affect Wound Healing

  • Nutrition: Positive nitrogen balance is crucial for protein synthesis needed for healing.

  • Blood flow and oxygen delivery: Adequate circulation is essential.

  • Immune strength: A robust immune system helps prevent infection.

  • Infection: The single most significant factor in delayed wound healing.

  • Foreign bodies: Can impede healing.

  • Mechanical factors: Tension or pressure on the wound.

Dysfunctional Wound Healing

  • Wound Rupture: High tension causes the wound to open; e.g., an abdominal wall wound rupturing from coughing.

  • Wound dehiscence: Previously closed wound edges open and rupture.

  • Wound evisceration: Internal tissues and organs protrude from an open wound; requires immediate protection with sterile, saline-moistened dressings.

  • Keloid formation: Hyperplastic epithelialization leading to a hypertrophic scar that extends beyond the original wound boundaries.

  • Contractures: Inflexible shrinkage of a wound, which can limit mobility (e.g., after a burn).

  • Stricture: Narrowing of an open area; e.g., esophageal stricture.

  • Fistula: Abnormal connection between two structures; e.g., tracheoesophageal fistula.

  • Adhesion: Abnormal bands of internal scar tissue that can limit organ mobility.

Innate Versus Adaptive Immunity

Innate Immunity (Nonspecific, First Line of Defense)

  • Barriers: Nonspecific but immediate recognition of nonself (not specific pathogens).

    • Includes skin, mucous membranes, chemicals (e.g., pH of GI tract, enzymes in tears), and microbiome.

    • Not completely impenetrable.

  • Inflammatory response: Vascular reaction from damage or trauma.

    • Nondiscriminatory: same sequence regardless of cause, local and systemic.

    • Acute phase: Immediately after injury until threat is eliminated; involves vasodilation/vasoconstriction, phagocytosis, fibrinogen.

    • Chronic phase: If acute phase does not resolve issue; lasts until healing is complete, often occurs in presence of resistant organisms.

  • Key Cells: Monocytes/macrophages function in phagocytosis, release cytokines, and present antigens.

  • Secretory products: Hydrolytic enzymes, TNF-alpha, interleukins.

  • Cytokines: Chemical signals produced by WBCs; regulate and coordinate the immune system and inflammation.

  • Natural Killer (NK) cells: Granular lymphocytes that destroy tumor cells and virus-infected cells.

  • Pyrogens: Released by bacteria or after exposure; cause systemic inflammatory response (fever) to create an unfavorable environment for bacterial proliferation.

  • Interferons: Released from virus-infected cells; bind to uninfected cells, causing them to release an enzyme that prevents viral replication.

  • Complement proteins: Plasma proteins that enhance antibodies; activated by antigens and play a role in immune/inflammatory response.

Adaptive (Acquired) Immunity (Specific, Second Line of Defense)

  • Characteristics: Slower to respond, highly specific response, develops memory for future encounters.

  • Components: Lymphocytes (T and B cells).

    • T cells: Mediate cell-mediated immunity.

    • B cells: Mediate antibody-mediated (humoral) immunity.

  • Recognition: Distinguishes self vs. nonself based on MHC (Major Histocompatibility Complex), also known as HLA (Human Leukocyte Antigen).

Cell Types in Adaptive Immunity

  • Antigen-presenting cells (APCs): Macrophages and dendritic cells present antigens to activate T cells.

  • T cells:

    • CD4 cells: Helper T cells; orchestrate immune responses.

    • CD8 cells: Cytotoxic T cells; directly destroy infected or cancerous cells.

    • HIV specifically damages CD4 cells.

  • B cells and Plasma Cells:

    • Antigens activate specific B cells.

    • Activated B cells transform into plasma cells that produce antibodies (immunoglobulins, Igs).

    • This is known as antibody-mediated or humoral immunity.

    • Primary response: First exposure to antigen; there is a lag time before Ig levels increase, with IgM being the first antibody produced.

    • Memory cells: Activated B cells also form memory cells, which provide a quicker and stronger response upon subsequent exposure.

    • Secondary response: Any exposure after the first leads to rapid increase in IgG levels (memory cell response), neutralizing the antigen before disease symptoms appear.

Immunoglobulins (Igs) - Antibody Subtypes

  • Produced by B cells; bind to specific antigens.

  • IgM: First antibody produced during a primary immune response.

  • IgG: Most abundant antibody; high levels in secondary responses due to memory cells.

  • IgA: Primarily found in secretions (tears, saliva, respiratory/GI fluids, breast milk).

  • IgE: Usually present in very low concentrations; elevates during allergic reactions and parasitic infections.

  • IgD: Hypersensitivity reactions; comprises only 1\% of immunoglobulins.

Active Acquired vs. Passive Acquired Immunity

  • Active Acquired Immunity:

    • Achieved through exposure to an antigen (illness or vaccination).

    • Activates the immune system and produces memory cells, providing long-term immunity.

  • Passive Acquired Immunity:

    • Individual receives pre-made antibodies.

    • Provides immediate, but short-term, immunity.

    • Examples: Hepatitis B immunoglobulin (HBIg) or antibodies transferred in breast milk.

Vaccines

  • Specific formulation containing a weakened, non-disease-producing pathogen.

  • Exposes the body to the antigen to stimulate an immune response and produce memory cells without causing the disease.

Basic Immune Disorders

Categories of Immune Disorders

  • Overreaction: Hypersensitivity reactions.

  • Underreaction: Immunodeficiency.

  • Self-attack: Autoimmune disorders.

Hypersensitivity Reactions (Overreaction)

  • Type I: Immediate (Allergies/Atopic Disorder):

    • Process: Allergen interacts with an APC; B cells activate and produce IgE; IgE binds to mast cells, causing degranulation (release of chemicals like histamine, prostaglandins, leukotrienes).

    • Symptoms: Induced by released chemicals; can be local (hives, nasal discharge, allergic gastroenteritis, bronchial asthma) or systemic.

    • Allergic Rhinitis: 50\% of U.S. population test positively; causes mucus hypersecretion, bronchiole constriction, pale nasal mucosa, watery eyes, sneezing.

    • Anaphylaxis: Severe, life-threatening systemic allergic response. Symptoms include urticaria, bronchoconstriction, laryngeal edema, angioedema. Can be fatal within minutes. Treated with EpiPen (epinephrine).

  • Type II: Cytotoxic Hypersensitivity:

    • Igs (IgG or IgM) attack antigens on the cell surface, leading to antibody-mediated cell lysis (e.g., via complement activation and phagocytosis).

    • Example: Blood transfusion reaction.

  • Type III: Immune Complex Hypersensitivity:

    • Antigen-antibody complexes are deposited in tissues, activating the complement system and causing tissue damage.

    • Can be systemic (e.g., Systemic Lupus Erythematosus) or localized (e.g., Rheumatoid Arthritis).

  • Type IV: Delayed Hypersensitivity:

    • T cell mediated, not antibody-mediated.

    • Previous exposure to antigen primes T cells.

    • T cell attack (cytokine release, tissue injury, fibrosis) occurs days after initial exposure.

    • Examples: Poison ivy, transplant rejection, Mantoux test for tuberculosis.

Autoimmune Disorders (Attack “Self” Cells)

  • Immune system cannot recognize itself and mounts an immune response against self-antigens (autoantibodies or T cell-mediated).

  • Can be organ-specific or systemic.

  • Underlying etiology: Often unknown.

  • Molecular mimicry: Body’s antigens resemble an infectious agent, leading the immune system to mistakenly attack the body’s own cells.

    • Example: Rheumatic fever, where antistreptococcal antibodies attack heart valves.

  • Known predictors: Genetics, female sex, abnormal stressors.

  • Frequently progressive relapsing-remitting disorders with exacerbations and remissions.

  • Diagnosis often involves eliminating other possibilities.

Specific Autoimmune Disorders

  • Systemic Lupus Erythematosus (SLE):

    • Multi-system disease with antinuclear antibodies (ANA’s) present.

    • Antibody complexes are deposited in various tissues.

    • Chronic disease with periods of remission and exacerbations.

    • Symptoms: Skin rash (classic butterfly rash across cheeks), joint inflammation, kidney damage, vasculitis, Raynaud’s phenomenon.

    • Risk factors: Genetic predisposition, environmental factors (e.g., EBV infection), and hormonal components.

  • Rheumatoid Arthritis (RA):

    • Chronic joint inflammation, may also affect other tissues.

    • Risk factors: Genetic factors, environmental factors (e.g., infections), hormonal influence (females are more likely).

    • Joint typical presentation: Symmetrical, tender, swollen joints (fingers, wrists, knees, hips most common).

    • Symptoms: Painful, stiff joints for 30 minutes or more in the morning.

    • Pathology: Involves antigen presentation, T helper cell activation (CD4), B cell activation leading to plasma cells and antibody production, macrophage involvement, and cytokine release (interleukins, TNF) leading to joint inflammation and pannus formation (abnormal granulation tissue).

  • Scleroderma (Systemic Sclerosis):

    • Abnormal accumulation of fibrous tissue in the skin and organs.

    • Associated with several gene mutations.

    • Inflammatory reaction with injury to the endothelium.

    • Most noticeable change: “Tightening” of skin; skin appears smooth, shiny, and stretched.

    • Contractures of fingers may occur.

    • CREST syndrome (a type of scleroderma): Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia.

    • Diagnosis: Elevated ANA’s, “ground glass” appearance in lungs.

    • Treatment: NSAIDs, corticosteroids, immunosuppressants.

Immunodeficiency (Diminished or Absent Immune Response)

  • Increases vulnerability to opportunistic infections.

  • Can be acute or chronic.

  • Types: Primary (congenital, present at birth) or secondary (acquired due to infection, chemotherapy, immunosuppressive drugs, etc.).

  • Diagnosis: Clinical suspicion based on recurrent or persistent infections, alongside blood analysis (immunoglobulin levels, WBC count, B- and T-cell counts).

  • Treatment: Individualized, depending on the deficiency (e.g., gamma-globulin, bone marrow transplants, thymus transplants).

  • Precautions: Reverse isolation precautions, careful evaluation of necessity for vaccines.

Immunity Across the Life Span

  • Infancy: Immunity based on maternal IgG for 3 to 6 months (temporary passive immunity); breastfeeding transfers IgA; vaccinations provide additional protection.

  • Adolescence: Hormonal changes impact the immune system, as B cells and macrophages have hormone receptors; increased risk for inflammatory and autoimmune diseases.

  • Immune dimorphism: Sexes respond differently to infection/vaccination.

  • Aging (Immune senescence): Decreases immune response; lower B- and T-cell production but increased apoptosis of these cells.

  • Age-related changes are multifactorial; comorbidity significantly impacts immunity, and autoimmune disorders become more likely due to misinterpretation of signals.

Developing a Strong Immune System

  • Avoid over-sanitizing the environment to build immunity.

  • Smoking cessation and moderate alcohol consumption.

  • Regular exercise.

  • Vaccinations.

  • Increased fluid intake.

  • Well-balanced diet.

  • Adequate sleep.

  • Weight management.

  • Reducing stress.

Infection and Portal of Entry

Portal of Entry

  • Skin: Natural barrier due to thickness and low pH; harbors normal flora (e.g., Staphylococcus, Streptococcus, Candida). Intact skin is a crucial barrier.

  • Respiratory tract: Possible entry for thousands of microorganisms (viruses, bacteria, fungi) despite cilia, mucous secretions, and specialized immune cells.

  • Gastrointestinal tract: Contaminated food and drink, fecal-oral transmission. Stomach pH, mucus, and normal flora prevent many infections.

  • Genitourinary tract: Urethra is a common route. Flow of urine and low pH of the vagina help prevent infections. Females are at greater risk of UTIs. Semen and vaginal secretions can transmit infectious agents.

  • Blood-blood transmission: Via blood transfusions, sharing needles. Also through mucous membranes, eyes, and skin (necessitating universal precautions).

  • Maternal-fetal transmission: Some pathogens cross the placental barrier or are transmitted during childbirth, causing congenital infections (e.g., CMV, rubella, herpes simplex virus).

Bacterial Infections

  • Pseudomonas aeruginosa:

    • Gram-negative bacterium.

    • Most common pathogen isolated from hospitalized patients after 1 week or more.

    • Can infect many systems, potentially life-threatening; lung infection may lead to pneumonia.

  • Bacterial Meningitis:

    • More severe than viral meningitis, can be fatal.

    • Common signs: Fever, nuchal rigidity (neck stiffness), headache, photophobia.

    • Specific signs: Kernig’s and Brudzinski’s signs.

    • Diagnosis: Lumbar puncture is needed.

    • Neisseria meningitidis: Droplet transmission person-to-person. May cause meningococcemia (systemic infection) with petechiae and potential gangrene. Meningococcal vaccine available.

    • Haemophilus influenzae: Gram-negative, subtype b is most virulent. Children and elderly most at risk. Childhood immunization has significantly reduced infection rates.

  • Escherichia coli (E. coli):

    • Many different strains.

    • E. coli O157:H7: May cause severe disease. Lives in intestines of healthy cattle; undercooked meat is a common transmission route. Can lead to Hemolytic Uremic Syndrome (HUS).

  • Diphtheria (Corynebacterium diphtheriae):

    • Bacteria secretes a toxin that produces a pseudomembrane in the throat.

    • Treated with antitoxin.

    • DTaP vaccine protects against Corynebacterium diphtheriae, Bordetella pertussis, and Clostridium tetani.

  • Pertussis (Bordetella pertussis):

    • Also known as “whooping cough.”

    • Produces a toxin that affects ciliary action of the respiratory tract.

  • Tetanus (Clostridium tetani):

    • Produces a toxin that results in muscle contraction, causing “lockjaw.”

  • Botulism (Clostridium botulinum):

    • Produces a toxin that results in muscle flaccidity.

    • Used clinically as “Botox.”

Viral Infections

  • Common cold:

    • Adults experience 3-4 colds per year.

    • Caused by Rhinovirus, Adenovirus, Coronavirus.

    • Transmitted via direct contact or droplet.

  • Influenza virus:

    • 3 major types: A, B, C.

    • Causes annual outbreaks and can lead to pandemics.

    • High mutation rate leads to challenges in vaccine development and necessitates seasonal vaccines.

    • Abrupt onset of symptoms, lasting 2 weeks or longer.

  • Epstein-Barr Virus (EBV):

    • Cause of mononucleosis; over 90\% of population infected, but not all develop mononucleosis.

    • Symptoms: Pharyngitis, severe fatigue, lymphadenopathy, and splenomegaly.

  • Cytomegalovirus (CMV):

    • Causes a wide range of disorders, including birth defects and mononucleosis-like symptoms in adults.

    • Can cause congenital infections.

    • Immunocompromised individuals are at high risk.

Parasitic Infections

  • Amebiasis (Entamoeba histolytica) and Giardiasis (Giardia lamblia):

    • Water-borne protozoan infections.

    • May be asymptomatic or develop into severe dysentery.

  • Malaria (Plasmodium protozoan):

    • Transmitted by the Anopheles mosquito.

    • Destroys RBCs, affects liver and spleen.

    • Symptoms: Jaundice, chills, hemolytic anemia, hepatomegaly, splenomegaly.

    • Treated with chloroquine; malaria prophylaxis available.

  • Prions:

    • Cause fatal degenerative neurological diseases.

    • Creutzfeldt-Jakob Disease (CJD): Results in a spongiform appearance of the brain.

    • Bovine Spongiform Encephalopathy (“Mad cow” disease): Spread via meat-and-bone meal fed to cattle.

Mycoplasma pneumoniae Infection

  • Small bacteria, lacks a cell wall.

  • Infection referred to as “walking pneumonia,” common in school-aged children.