Cellular and Non-cellular Pathogens and the Immune System
Cellular and Non-Cellular Pathogens
Pathogens are classified into two categories: cellular and non-cellular.
Bacteria
Unicellular prokaryotic organisms.
They reproduce through binary fission.
Bacteria release toxins or enzymes that negatively affect cell functioning or lead to cell death.
Fungi
Eukaryotic organisms.
Characterized by spore formation.
Viruses
Non-cellular pathogens.
Consist of genetic material (either DNA or RNA) stored within a capsid (a protein coat).
Require a host cell to replicate.
Prions
Non-cellular pathogens made entirely of protein.
They cause other proteins to misfold.
They specifically affect the brains of animals, leading to diseases such as Mad cow disease.
Protozoa
Single-celled eukaryotic organisms.
Worms
Multicellular parasites.
Require a host to feed on and reproduce.
The First Line of Defense
The primary barrier system is characterized by physical, chemical, and microbiological barriers designed to keep pathogens out of a host organism.
Barriers in Plants
Physical: Includes structures like bark.
Chemical: Includes substances such as Glucanases, which defend the plant against fungal pathogens.
Barriers in Animals
Physical: Intact skin acts as a primary physical barrier.
Chemical: Stomach acid is used to kill swallowed pathogens.
Microbiological: Consists of non-pathogenic bacteria (normal flora) that prevent the growth or colonization of pathogens by competing for space and resources.
The Second Line of Defense: Innate Immunity
This line of defense provides a non-specific and immediate response against potential pathogens.
All cells involved are leukocytes (white blood cells).
Lysosomes () contain enzymes that target and destroy foreign material.
Phagocytes
Immune cells that engulf foreign or dead material via endocytosis.
This process is termed phagocytosis.
Types include neutrophils, dendritic cells, and macrophage cells.
Antigen-Presenting Cells (APCs)
After destroying foreign material, APCs display fragments of the antigen on their MHC class II markers.
This interaction allows them to activate the adaptive immune system.
Primary APCs include dendritic cells and macrophages.
Cytokines
Signaling molecules released by immune cells to communicate and coordinate responses.
Interferons
A specific type of cytokine released by virus-infected cells.
They interact with neighboring cells to trigger changes that inhibit viral spread.
Natural Killer (NK) Cells
These cells target and destroy abnormal or infected cells.
Cell survival is determined by the MHC class I markers, which can be altered by disease.
If the killer inhibitory receptor detects a sufficient number of MHC class I markers, the cell survives.
If the killer inhibitory receptor detects an insufficient number of MHC class I markers, cell death is triggered.
Mast Cells
Activate when they detect injury or are stimulated by antigens or allergens.
Upon activation, they release histamine, a critical molecule in the inflammatory response.
Eosinophils
Large granulated cells.
Upon contacting a large pathogen, they undergo degranulation, releasing toxic chemicals such as DNase, RNase, and protease to destroy the pathogen.
The Complement System
Consists of complement proteins within the blood.
In the presence of a pathogen, these proteins react with one another in a complement cascade.
Opsonization: Complement proteins stick to the outside surface of pathogens, making them easier to identify and engulf by phagocytes.
Chemotaxis: Complement proteins gather near a pathogen and attract phagocytes to the site of infection.
Lysis: Proteins form a membrane attack complex (MAC), which causes the cell to burst (lysis) and be destroyed.
Fever and Inflammation
Fever
A rise in core body temperature in response to an infection.
Many pathogens are unable to survive at elevated temperatures.
Inflammation
A result of increased blood flow, which brings immune cells and chemicals to an infected area, characterized by redness and swelling.
Initiation: Pathogens enter the body; platelets surround the area to prevent further entry; injured cells attract phagocytes to engulf pathogens.
Vasodilation: Mast cells release histamine, causing blood vessels to widen (vasodilation) to increase blood flow and the permeability of vessels for immune cell migration.
Migration: Phagocytes migrate to the injured site for phagocytosis; complement proteins are attracted to pathogens; pus (composed of dead immune cells and pathogens) may form.
The Third Line of Defense: Adaptive Immunity
Acquired during life, this response is specific and provides long-term immunological memory.
It is initiated by the presentation of non-self antigens by APCs.
Humoral Immunity
A naive B cell with a complementary receptor to the antigen is selected.
A helper T cell with a complementary receptor to the antigen present on the MHC class II marker of the naive B cell is selected.
Cytokines are released, stimulating clonal expansion and differentiation into memory B cells (for memory) and plasma B cells (to secrete antibodies).
Antibody Functions
Neutralization: Blocking the binding sites of pathogens to prevent host cell attachment.
Agglutination: Binding to antigens on separate pathogens to form large antigen-antibody complexes, aiding phagocyte recognition.
Immobilization: Restricting pathogen movement through complex formation.
Opsonization: Binding directly to the pathogen surface to facilitate phagocytosis.
Activation of complement proteins: Facilitating the complement system by attaching to pathogen surfaces.
Cell-Mediated Immunity
A naive T cell with a receptor complementary to the MHC II marker on an APC is selected.
A helper T cell with a complementary receptor to the antigen is selected.
Cytokines trigger clonal expansion and differentiation.
This produces memory T cells and cytotoxic T cells, which release toxins and chemicals to destroy infected cells.
Antibody Structure
Antibodies consist of two heavy chains and two light chains.
They feature a variable region (antigen-binding site) and a constant region (stem).
Chains are held together by disulfide bonds.
Self vs. Non-Self Recognition
Self-antigens: Molecules on the surface of an organism's own cells that identify them as "self," preventing immune attacks.
MHC (Major Histocompatibility Complex)
MHC Class I markers: Found on all nucleated cells in the body.
MHC Class II markers: Found only on specialized antigen-presenting cells.
Non-self antigens: Markers on foreign cells recognized as not belonging to the body, activating an immune destruction response.
Antigen Malfunctions
Autoimmune diseases: The immune system identifies the body's self-antigens as foreign (non-self) and attacks healthy cells. Examples include Lupus and Type 1 diabetes.
Allergies: The immune system overreacts to an allergen, which is a non-self antigen that is actually harmless (a non-pathogen).
Allergic Reactions (Mechanism)
Exposure to an allergen.
Recognition of the antigen as a pathogen; a B cell is selected and differentiates.
Plasma B cells secrete IgE antibodies, which bind to mast cells.
Re-exposure to the same allergen; the allergen binds to the IgE antibodies already on the mast cells, causing them to degranulate (activate).
Histamine is released, causing vasodilation and increased permeability. Symptoms include swelling and redness.
The Lymphatic System
A large network of vessels through which lymph (a pale fluid high in leukocytes) flows.
Primary Lymphoid Tissue
Bone marrow: Site of B cell maturation and leukocyte creation.
Thymus: Site of T cell maturation.
Secondary Lymphoid Tissue
Lymph nodes: Sites for maintaining lymphocytes and initiating the adaptive immune response.
Lymphatic Flow
Fluid leaks from blood vessels into tissues; this leakage increases during inflammation.
Lymphatic capillaries collect this fluid and any pathogens.
The system has thin walls and relies on muscle movement (not the heart) to squeeze fluid through.
Valves ensure one-way flow.
Lymphatic Surveillance
Afferent vessels: Deliver lymph from tissues to lymph nodes. Lymph travels through clusters of B and T cells to find matching receptors.
Efferent vessels: Collect lymph from nodes and return it to circulation.
If an antigen matches a lymphocyte receptor, it undergoes clonal expansion, resulting in swelling of the lymph node.
Immunity Categories and Medical Interventions
Innate Immunity: Natural, non-specific immunity without medical intervention.
Adaptive Immunity
Natural Active: Individual produces their own memory cells and antibodies after exposure.
Natural Passive: Individual acquires pre-made antibodies (e.g., via breastfeeding or the placenta). No immunological memory is formed.
Artificial Active: The body makes its own antibodies and memory cells due to medical intervention, such as vaccines.
Artificial Passive: The body acquires antibodies via external medical intervention, such as antivenoms.
Vaccines
Contain attenuated (weakened) or dead pathogens to generate immunity without causing illness.
Immune Responses
Primary Immune Response: Slow, as APCs require time to find matching T and B cells for clonal expansion.
Secondary Immune Response: Pre-existing memory cells identify the antigen, resulting in a large, rapid production of antibodies.
Booster Vaccines
Memory cells may die off over long periods. Boosters are given years later to stimulate existing memory cells and maintain long-lasting immunity.
Herd Immunity
When a majority of a population is vaccinated, pathogens cannot easily spread, protecting those who are unvaccinated or cannot be vaccinated.
Epidemiology and Disease Transmission
Infectious Disease: Caused by a pathogen (e.g., COVID).
Non-infectious Disease: Not caused by a pathogen (e.g., diabetes).
Contagion: How easily a pathogen is transmitted between people.
Virulence: How severe the disease caused by the pathogen is.
Emerging Diseases: Diseases that have not occurred in humans before, or have existed historically but were only recently discovered to be caused by a specific pathogen (e.g., COVID).
Re-emerging Diseases: Diseases once controlled that are becoming health problems again, or that previously only affected small populations (e.g., Tuberculosis/TB).
Factors Contributing to Emergence/Re-emergence
Zoonosis (animal-to-human transmission).
Evolution of the pathogen.
Insufficient vaccination.
Global travel.
Increasing human population.
Poor hygiene.
Epidemiological Terms
Outbreak: Sudden, unexpected increase in disease occurrence.
Epidemic: Rapid increase of a disease within a specific population.
Pandemic: Infectious disease spreading to multiple countries/continents (e.g., COVID).
Endemic: Disease occurring at a relatively baseline level in a population (e.g., Flu in Australia).
Historical Impact on Indigenous Australians
In , British colonists and convicts brought diseases like Smallpox to Australia, causing devastating sickness and death among Aboriginal populations.
Reasons for Susceptibility
Lack of immunity: Europeans had developed immunity over time, whereas Aboriginal individuals had no immunological memory of these pathogens.
Lack of knowledge: There was an absence of knowledge regarding treatment and control of these new diseases.
Disruption: Colonization restricted access to food, water, and traditional medical practices.
Pathogen Identification and Control
Methods of Identification
Physical: Visualizing the pathogen structure using a microscope.
Phenotypic: Using agar plates to facilitate growth for identification.
Immunological (Serology): Diagnosis based on antibodies/antigens in serum. SANDWICH ELISA (Enzyme-Linked Immunosorbent Assay) involves:
Coating a plate with pathogen-specific antibodies.
Adding patient serum (antigen binds if present).
Adding a second enzyme-tagged antibody.
Adding a substrate to produce a color change signal.
Molecular: Genetic sequencing or hybridization-based detection using labeled segments of genetic material complementary to the pathogen.
Modes of Transmission
Airborne: Inhaling particles from sneezing, coughing, or talking.
Droplet: Pathogen-containing droplets falling on surfaces and being transferred to eyes, nose, or mouth.
Direct Physical: Touch or sexual contact.
Indirect Physical: Contaminated food, water, or vectors.
Faecal-oral: Pathogens from feces consumed by another person.
Control Strategies
PPE (Personal Protective Equipment).
Screening and Quarantine/Isolation.
Education and Vaccination.
Disinfectants: Applied to non-living surfaces.
Antiseptics: Applied to living tissues.
Antibiotics and Antivirals.
Immunotherapy
Medical intervention to alter immune system functioning.
Activation Immunotherapy: Used to induce or amplify an immune response (e.g., for cancer).
Dendritic Cell Therapy: Priming dendritic cells with tumor-associated antigens (TAA) to train the immune system.
CAR T Therapy: T cells are extracted and modified with a Chimeric Antigen Receptor (CAR) to seek and destroy cancer cells.
Antibody Therapy: Using monoclonal antibodies (mAbs).
Cytokine Therapy: Using signaling molecules like interferons.
Suppression Immunotherapy: Used to prevent or reduce an immune response (e.g., for autoimmune diseases).
Monoclonal Antibodies (mAbs)
Laboratory-made proteins. Production involves:
Isolating the antigen on a desired cell.
Vaccinating an animal to produce antibodies.
Extracting B-lymphocytes.
Fusing B-lymphocytes with myeloma cells (rapidly dividing cancer cells) to form hybridomas.
Cloning hybridomas to produce large amounts of antibodies.
Administering the collected antibodies to the patient.
mAbs Action Against Cancer
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): mAbs bind to cancer cells, leading NK cells to recognize and destroy them.
Complement Activation: mAbs bind to cancer cells and interact with complement proteins to destroy the cell.
Checkpoint Inhibition: Cancer cells often stimulate immune checkpoints to suppress the immune system. mAbs block these checkpoints so the immune system remains active against the cancer.
Conjugated mAbs: Have medicines or radioactive substances attached to deliver directly to cancer cells.
Naked mAbs: Have no attached molecules.
Traditional vs. Immunotherapy
Cancer: Traditional therapies like chemotherapy and radiotherapy kill all rapidly dividing cells (causing hair loss). Immunotherapy targets cancer cells specifically.
Autoimmune: Traditional treatments use immunosuppressants which lead to immunodeficiency. Immunotherapy can inhibit only specific autoreactive B and T cells or cytokines, leaving the rest of the immune system intact.