Microbe-Human Interactions: Colonization & Disease

Interactions Between Microbes and Humans Overview

• Humans coexist with both beneficial and harmful microorganisms from birth.
• Some microbes can cause disease and are called pathogens.
• Pathogenicity defines a microbe's ability to cause disease.
• Virulence determines the severity of the infection.
• Microbes enter the body through portals of entry like the skin and mucous membranes.
• Microbes attach to tissues using structures like fimbriae or capsules.
• Microbes produce virulence factors, such as toxins and enzymes, to cause disease.
• Diseases are transmitted via direct or indirect contact.
• Epidemiologists track diseases, using data such as incidence and prevalence, to control outbreaks.

Colonization vs. Infection vs. Disease

• Colonization occurs when microbes reside in the body without causing harm.
• Infection occurs when microbes invade and multiply within the body.
• Disease occurs when an infection leads to tissue damage and symptoms.

Normal Biota and the Microbiome

• Normal biota are found on the skin, in the respiratory and gastrointestinal tracts, and in other areas.
• The Human Microbiome Project reveals a greater variety of normal biota than previously known.

Pathogenicity vs. Virulence

• Pathogenicity refers to the ability of a microbe to cause disease.
• Virulence refers to the degree of damage a pathogen causes.
• True pathogens cause disease in healthy individuals. For example, the influenza virus.
• Opportunistic pathogens cause disease in immunocompromised individuals. For example, Candida albicans.

Steps in Disease Development

• Portal of Entry: Pathogens enter the body through openings like the skin and mucous membranes.
• Attachment: Pathogens adhere to host tissues using fimbriae, pili, or capsules.
• Invasion: Microbes evade host defenses, such as phagocytosis.
• Multiplication: Pathogen spreads and damages tissue.
• Disease Development: Symptoms become apparent.
• Portal of Exit: Pathogens leave the body to infect new hosts.

Polymicrobial Infections

• Involve multiple pathogens simultaneously.
• An example is dental cavities caused by Streptococcus and other bacteria working together.

Infectious Dose (ID)

• The minimum number of microbes required to cause an infection.
• A low ID indicates high virulence, such as with Mycobacterium tuberculosis.
• A high ID indicates lower virulence, such as with Vibrio cholerae.

Three Ways Microbes Cause Tissue Damage

• Exoenzymes: Break down host tissues, examples include collagenase and hyaluronidase.
• Toxins:
  • Exotoxins are secreted proteins, such as botulinum toxin.
  • Endotoxins are part of the Gram-negative bacterial cell wall, specifically lipopolysaccharides.
• Host immune response: Immune reactions like inflammation and fever can damage tissues.

Stages of Disease Progression

• Incubation Period: No symptoms are present.
• Prodromal Stage: Mild symptoms start to appear.
• Period of Invasion: Severe symptoms manifest.
• Convalescent Period: The body recovers.

Types of Infections

• Local infection: Confined to one area, such as a skin abscess.
• Focal infection: Spreads from one area to another.
• Systemic infection: Affects the entire body.
• Mixed infection: Involves multiple pathogens.

Reservoirs & Transmission

• Reservoirs house pathogens, including humans, animals, and soil.
• Carriers are infected individuals who spread the disease.
• Transmission Modes:
  • Direct Contact: Person-to-person.
  • Indirect Contact: Through fomites (inanimate objects).
• Vector Transmission: Via insects. An example is mosquitoes.

Healthcare-Associated Infections (HAIs)

• Acquired in hospitals, often due to equipment, procedures, or drug-resistant bacteria.
• Common HAIs include urinary tract infections (UTIs) and pneumonia.

Epidemiology & Disease Tracking

• Incidence: New cases in a population over a specific time.
• Prevalence: Total cases at a given time.
• Types of Epidemics:
  • Point-source: Single exposure, such as food poisoning.
  • Common-source: Continuous exposure, from contaminated water.
  • Propagated: Person-to-person spread, classic for influenza.

Koch’s Postulates (Disease Causation)

• The suspected pathogen must be present in every case of the disease.
• It must be isolated and grown in pure culture.
• The pure culture must cause the disease in a healthy host.
• The same pathogen must be re-isolated from the newly infected host.
• Limitations: Some microbes can't be cultured, and some diseases have multiple causes.

Herd Immunity

• High vaccination rates protect vulnerable individuals by reducing disease spread.

Host Defenses I – Overview and Innate Defenses

• The immune system protects the body from pathogens using cells, fluids, and organs
• It functions with three lines of defense.
• First Line: Physical and chemical barriers, such as skin and mucous membranes.
• Second Line: Innate immune responses, including phagocytes and inflammation.
• Third Line: Adaptive immunity with T and B lymphocytes.
• The combined effort of the Lymphatic system, mononuclear phagocyte system (MPS), extracellular fluid (ECF), and blood vascular system cooperate to eliminate invaders.

Three Lines of Defense

• First Line: Skin, mucous membranes, normal microbiota; prevents pathogen entry.
• Second Line: Phagocytes, inflammation, fever, antimicrobial proteins; rapid, nonspecific response.
• Third Line: T and B lymphocytes, antibodies; specific, long-term immunity.

Importance of Markers in Immunity

• Markers on cells help differentiate self from non-self.
• Second & third lines of defense target invaders based on these markers.

Body Systems Involved in Immunity

• Lymphatic system: Filters lymph, returns fluid to the circulatory system.
• Circulatory system: Blood transports immune cells.
• Mononuclear phagocyte system (MPS): Macrophages patrol tissues and engulf invaders.
• Extracellular fluid (ECF): Facilitates immune cell movement through tissues.

The Lymphatic System

• Functions:
• Returns extracellular fluid to the circulatory system.
• Drains inflammation-related fluids.
• Immune surveillance through lymphocytes, phagocytes, and antibodies.
• Lymphoid Organs:
  • Primary organs include Bone marrow (B & T cell production) and Thymus (T cell maturation).
  • Secondary include Lymph nodes, spleen, tonsils, and gut-associated lymphoid tissue (GALT).

Blood Cells in Innate Immunity

• Granulocytes: Neutrophils, eosinophils, and basophils involved in inflammation and phagocytosis.
• Macrophages: Mature monocytes that engulf pathogens and present antigens.
• Dendritic cells: Initiate adaptive immunity.

Mononuclear Phagocyte System (MPS) & Histocytes

• The MPS is a network of macrophages that engulfs pathogens.
• Histiocytes are specialized, tissue-resident macrophages. For example, Kupffer cells in the liver.

Cytokines & Their Roles

• Cytokines are signaling proteins that regulate immune responses.
• IL-1 (Interleukin-1) is a pro-inflammatory cytokine which promotes fever & inflammation.
• IL-10 (Interleukin-10) is an anti-inflammatory cytokine that suppresses excessive immune responses.

First Line of Defense: Physical & Chemical Barriers

• Skin: Keratin provides a tough barrier.
• Mucous Membranes: Trap microbes in mucus.
• Chemical Defenses:
• Lysozyme (tears, saliva) breaks bacterial cell walls.
• Acidic pH (stomach, skin) kills pathogens.
• Defensins (antimicrobial peptides) destroy bacterial membranes.
• Normal Microbiota: Compete with pathogens for nutrients and space.

Second Line of Defense: Innate Immune Responses

• Phagocytosis: Engulfing and digesting pathogens.
• Inflammation: Localized response to injury or infection.
• Fever: Increases metabolism; inhibits pathogens.
• Antimicrobial Proteins: Directly destroy microbes or enhance immunity.

Steps of Phagocytosis

• Chemotaxis: Phagocytes follow chemical signals to infection.
• Adhesion: Phagocyte binds to pathogen.
• Engulfment: Pathogen is engulfed into a phagosome.
• Fusion: Phagosome fuses with lysosome to form a phagolysosome.
• Destruction: Enzymes digest the pathogen.
• Exocytosis: Debris is expelled.

Stages of Host DefensesInflammation

• Injury initiates it.
• Vasodilation occurs leading to increased blood flow with redness and heat.
• Permeability increases as fluid leaks causing swelling and pain.
• Migration of Neutrophils and Macrophages.
• Healing begins with tissue repair.

Fever: Mechanism & Function

• Triggered by pyrogens (fever-inducing molecules).
• Benefits:
  • Inhibits microbial growth.
  • Increases immune response speed.

Four Antimicrobial Products

• Complement System: Creates membrane attack complexes (MACs) to lyse bacteria.
• Interferons: Protects cells from viral infections.
• Restriction Factors: Prevents viral replication inside cells.
• Antimicrobial Peptides (AMPs): Destroy microbial membranes.

Adaptive Immunity and Immunization

• Adaptive immunity activates when innate defenses aren't enough.
• Adaptive immunity is highly specific, recognizing unique antigens and creating memory cells for long-term immunity.
• Adaptive immunity is acquired after exposure to an infection or vaccine.
• Adaptive immunity consists of lymphocyte development, antigen presentation and clonal selection, lymphocyte activation & proliferation, and T-Cell and B-Cell responses.

Adaptive Immunity vs. Innate Immunity

• Adaptive immunity is delayed, takes 3 to 5 days to activate.
• Innate immunity is immediate.
• Adaptive immunity recognizes specific antigens.
• Innate immunity is nonspecific.
• Adaptive immunity forms memory cells.
• Innate immunity has no memory.
• Macrophages and neutrophils are key cells in innate immunity.
• T cells and B cells are key cells in adaptive immunity.

Key Terminology

• Antigen (Ag): Molecule recognized by the immune system.
• Immunogen: Antigen that triggers a strong immune response.
• Epitope: Region on an antigen that immune cells recognize.

The Four Stages of Adaptive Immunity

• Stage I: Lymphocyte Development & Clonal Deletion - B & T cells originate in the bone marrow. - B cells mature in bone marrow; T cells mature in the thymus. - Clonal deletion eliminates self-reactive lymphocytes to prevent autoimmunity.
• Stage II: Antigen Presentation & Clonal Selection - Antigen-Presenting Cells engulf pathogens and display antigens on MHC molecules. - MHC-I presents to Cytotoxic T cells (CD8+) to kill infected cells. - MHC-II presents to Helper T cells (CD4+) to activate B & T cells.
• Stage III: Lymphocyte Activation & Proliferation - B & T cells recognize the antigen and proliferate into effector cells (attack the pathogen) and memory cells (provide long-term immunity).
• Stage IV: T-Cell & B-Cell Responses - T-Cell Response (Cell-Mediated Immunity) - Helper T cells (CD4+) activate other immune cells. - Cytotoxic T cells (CD8+) destroy infected cells. - Regulatory T cells (Tregs) suppress excessive immune responses. - B-Cell Response (Humoral Immunity) - Activated B cells become plasma cells which secrete antibodies.

Major Histocompatibility Complex (MHC)

• MHC molecules are self-markers on all cells.
• MHC-I is on all nucleated cells and interacts with CD8+ T cells.
• MHC-II is on APCs and interacts with CD4+ T cells.

B-Cell & T-Cell Receptors

• B-Cell Receptors (BCRs) bind free-floating antigens.
• T-Cell Receptors (TCRs) only recognize antigens when presented on MHC molecules.

Types of Antigens

• Alloantigens are found in different members of the same species. For example, blood group antigens.
• Superantigens trigger excessive immune responses, leading to cytokine storms.
• Haptens are small molecules that become antigenic when attached to larger proteins.

Antibody Structure & Function

• Antibodies (Immunoglobulins, Ig) are Y-shaped molecules made by B cells.
• Functions of Antibodies: - Neutralization blocks pathogen binding. - Opsonization marks pathogens for phagocytosis. - Complement Activation triggers the complement system.
• Types of Antibodies - IgG is the most abundant, crosses the placenta, and provides long-term immunity. - IgA is found in mucus & secretions, such as saliva, tears, and breast milk. - IgM is the first antibody produced during an infection. - IgE is involved in allergic reactions & parasitic infections. - IgD is a B-cell receptor; its function is unclear.

Primary vs. Secondary Immune Response

• Primary Response: Slower response, mostly IgM.
• Secondary Response: Faster, stronger memory response, mostly IgG.

Types of Adaptive Immunity

• Natural Active results from exposure to a pathogen. An example is an infection.
• Artificial Active results from vaccination. An example is the MMR vaccine.
• Natural Passive results from maternal antibodies such as found in Breast milk or via the placenta.
• Artificial Passive results from injected antibodies, such as antiserum or anti-venom.

Vaccines

• An effective vaccine should be safe with minimal side effects, provide long-term immunity, and elicit both B-cell & T-cell responses.

Hypersensitivity Reactions (Allergic & Autoimmune Responses)

• The immune system can overreact, which may lead to hypersensitivity reactions.
• These are divided into four types: - Type I (Immediate) – Allergies & Anaphylaxis - Type II (Cytotoxic) – Antibody-Mediated Cell Destruction - Type III (Immune Complex) – Antigen-Antibody Complex Deposition - Type IV (Delayed) – T-Cell Mediated Responses

Clinical Forms of Anaphylaxis & Their Fatality Risks

• Anaphylaxis is caused by the massive release of histamine and other mediators from mast cells.
• Cutaneous anaphylaxis is a localized reaction. It's less dangerous and usually resolves with antihistamines.
• Systemic anaphylaxis (Anaphylactic shock) is life-threatening.
• Causes bronchoconstriction, swelling of airways, and circulatory collapse. More often fatal due to airway obstruction and severe hypotension.
• Common triggers include Bee stings, peanut allergies, and certain medications. For example, penicillin.
• Treatment includes Epinephrine (EpiPen) to reverse symptoms.

Ways to Prevent or Short-Circuit Type I Allergic Reactions

• Avoidance of Allergens by eliminating contact with known allergens.
• Desensitization (Allergen Immunotherapy) through Repeated exposure to small amounts of an allergen to build tolerance.
• IgG blocking can prevent IgE binding.
• Pharmacological Treatment includes Antihistamines blocking histamine receptors, Epinephrine to reverse anaphylaxis, and Corticosteroids to reduce inflammation.

Immune Components Causing Cell Lysis in Type II Hypersensitivity

• Type II hypersensitivity reactions are antibody-mediated cytotoxic responses that may lead to cell lysis.
• IgG & IgM antibodies bind to target cells and mark them for destruction.
• Complement system triggers cell lysis via the membrane attack complex (MAC).
• Phagocytes (Macrophages & NK cells) destroy antibody-coated cells.
• Examples include Hemolytic disease of the newborn (HDN) via Rh incompatibility, and Blood transfusion reactions.

Rh Factor & Hemolytic Disease Prevention in Newborns

• The Rh factor is a protein on red blood cells.
• If an Rh-negative mother carries an Rh-positive fetus, her immune system can develop anti-Rh antibodies. This can attack fetal RBCs in a second pregnancy- Hemolytic Disease of the Newborn (HDN).
• Prevention: RhoGAM injection during pregnancy and after delivery prevents maternal anti-Rh antibody formation.

Type II vs. Type III Hypersensitivity

• Type II is antibody-mediated.
• Type III: is antigen-antibody complexes deposit in tissues.
• Type II: is antibody attack on cells directly with IgG, IgM.
• Type II damages RBCs, platelets, tissue cells.
• Type III: causes inflammation. An example is Hemolytic disease or Transfusion reactions.

Type IV Delayed Hypersensitivity Reaction

• Tuberculosis Skin Test (PPD Test) is one example.
• Type IV reactions are mediated by T cells, not antibodies.
• In TB skin testing, memory T cells react to Mycobacterium tuberculosis antigens, leading to localized swelling (delayed reaction in 24–72 hours).
• Other examples include Poison ivy contact dermatitis, and Graft rejection.

Classes of Grafts & Graft Rejection

• Autograft is from the same individual; No rejection.
• Isograft: is between identical twins; No rejection.
• Allograft is between individuals of the same species; Risk of rejection.
• Xenograft is between different species; High rejection risk.
• Host vs. Graft Disease (HVGD): Host immune system attacks the transplanted organ (T cells target foreign MHC molecules).
• Graft vs. Host Disease (GVHD): Transplanted immune cells (from bone marrow) attack the recipient’s tissues.
• Prevention: Immunosuppressive drugs (cyclosporine, corticosteroids) are administrated.

Autoimmune Diseases & Key Features

• Lupus (SLE): Systemic; affects skin, joints, kidneys (positive for anti-DNA antibodies).
• Rheumatoid Arthritis: Attacks joint cartilage & synovial membranes.
• Type 1 Diabetes Autoimmune destruction of pancreatic β-cells (insulin deficiency).
• Common Features Loss of self-tolerance, productions of autoantibodies.

Primary vs. Secondary Immunodeficiency

• . Primary: due to genetic factors.
• Secondary: is acquired
• Primary mutations are inherited.
• Primary onset is present from birth.