Comprehensive Study Notes: Chapter 7 - Dealing with Disease

Chapter 7: Dealing with Disease - Unit 4 Biology Area of Study 1

Detecting Pathogens (7A)

Antigens are defined as molecules, or parts of a molecule, that elicit an immune response. These molecules are typically found on the surface of pathogens or may be toxins released by bacteria. Their molecular composition can include proteins, sugars, and nucleic acids such as DNA or RNA. Antigens serve as the primary mechanism for the immune system to differentiate between 'self' and 'non-self' components.

Self-Antigens

Self-antigens are located on the surface of an organism's own cells to prevent the immune system from attacking 'self' tissue. In humans and other vertebrates, these are referred to as Major Histocompatibility Complex (MHC) markers. There are two primary types:

MHC Class I: These markers are found on all nucleated cells in the body. Notably, they are absent from Red Blood Cells (RBCs) because RBCs lack a nucleus.
MHC Class II: These markers are found specifically on specialized immune cells.

Antigens on Red Blood Cells (RBCs)

Red blood cells utilize glycoproteins as 'self' labels. The classification of blood groups is determined by the presence or absence of specific antigens and the corresponding antibodies in the plasma:

Group A: Contains A antigens on the RBC and Anti-B antibodies in the plasma.
Group B: Contains B antigens on the RBC and Anti-A antibodies in the plasma.
Group AB: Contains both A and B antigens on the RBC and has no antibodies in the plasma.
Group O: Contains no antigens on the RBC but has both Anti-A and Anti-B antibodies in the plasma.

Non-Self Antigens

Non-self antigens are those recognized as foreign by the immune system, thereby eliciting an immune response. Every individual possesses unique MHC markers to provide a basis for this distinction.

Malfunctions Involving Antigens

When the immune system fails to distinguish between self and non-self, it can lead to two types of malfunctions:

Autoimmune Disease: Occurs when the system attacks the body's own cells. Examples include Multiple Sclerosis, Type 1 Diabetes, and Rheumatoid Arthritis.
Allergic Reaction: An overreaction to a harmless non-self antigen (allergen). Common allergens include eggs, seafood, and peanuts.

Types of Pathogens

Pathogens are agents that cause disease. They are categorized into two structural types:

Cellular Pathogens (Living)

Bacteria: Unicellular prokaryotes that reproduce via binary fission. They cause disease by releasing toxins and enzymes that lead to cell lysis and death. While some are beneficial (e.g., in the GI tract), pathogenic bacteria are treated with antibiotics.
Fungi: Eukaryotic pathogens (including yeasts and moulds) that reproduce via spore formation (sexual or asexual). They possess a cell wall but no chloroplasts and thrive in moist conditions.
Protozoa: Single-celled eukaryotes that require a host for feeding and reproduction.
Multicellular Parasites: Such as worms (e.g., Tapeworms).

Non-Cellular Pathogens (Non-living)

Viruses: Composed of genetic material (DNA or RNA) encased in a protein coat called a capsid. They require a host cell for replication. Their antigens can mutate, which complicates the immune response.
Prions: Composed entirely of protein with no genetic material. They cause other proteins to misfold and are responsible for diseases such as bovine spongiform encephalopathy (Mad Cow Disease) in mammals.

Scale of Pathogens

The size of biological agents varies significantly:

Worms (e.g., Tapeworm): up to $10\,m$ to $1\,m$ .
Fungus (e.g., Trichophyton): approximately $1\,cm$ .
Protozoa (e.g., Plasmodium): $100\,\mu m$ to $10\,\mu m$ .
Bacteria (e.g., Neisseria meningitidis): $1\,\mu m$ .
Viruses (e.g., Rhinovirus): $100\,nm$ to $10\,nm$ .
Prions: $1\,nm$ .

The First Line of Defence (7B)

The first line of defence consists of innate, non-specific barriers that prevent pathogenic infection before it begins.

Types of Protection

Physical Barriers: Block or hinder pathogens from entering the body.
Chemical Barriers: Produce chemical substances that inhibit growth or destroy pathogens.
Microbiological Barriers: Consist of 'normal flora' (non-pathogenic bacteria) that prevent the growth of pathogens by competing for resources.

Barriers in Plants

Physical: Thick bark to prevent entry, waxy cuticles on leaves, thorns, and the closing of stomata.
Chemical: Tannins (toxic to insects), phenols (repel microorganisms), caffeine (toxic to insects and fungi), and enzymes that disrupt fungal cell membranes.

Barriers in Animals

Physical: Intact skin, mucous secretions, hairs in the respiratory tract, and cilia.
Chemical: Lysozyme enzymes in tears and saliva (destroy bacteria), acidic sweat, earwax with antibacterial compounds, antibacterial proteins in semen, low pH in the vagina, and stomach acid.
Microbiological: Normal flora found on the skin, in the gastrointestinal (GI) tract, and in the vagina.

The Second Line of Defence (7C)

The innate immune system activates if pathogens breach the first line. It is characterized by being non-specific (identical response regardless of pathogen) and having no immunological memory.

Cells of the Innate Immune System

Phagocytes (Neutrophils, Macrophages, Dendritic Cells): These cells recognize non-self pathogens and engulf them via endocytosis. The pathogen is enclosed in a vesicle that fuses with a lysosome, where enzymes digest it. If the cell is an 'Antigen-Presenting Cell' (APC), like a macrophage or dendritic cell, it displays fragments of the digested pathogen on its MHC Class II marker to alert the adaptive immune system.
Natural Killer (NK) Cells: Large granulated cells that target abnormal cells (cancer) and virus-infected cells. They utilize two receptors: the Killer Inhibitory Receptor (examines MHC I markers) and the Killer Activation Receptor (binds molecules on infected cells). If an NK cell detects a lack of MHC I markers on a target cell, the activation receptor triggers apoptosis (programmed cell death) via cytotoxic chemicals.
Mast Cells: Located in tissues; these detect injury and release histamine to initiate inflammation.
Eosinophils: Large granulated cells containing toxic chemicals used to destroy larger pathogens, such as parasites, that cannot be swallowed by phagocytes.

Non-Cellular Components

Cytokines: Signalling proteins that facilitate communication between immune cells. They guide cells to infection sites, induce fever/inflammation, and promote lymphocyte proliferation.
Interferons: A specific cytokine released by virus-infected cells that warns neighboring cells, making them less susceptible to infection and blocking viral translation.
Complement Proteins: Blood proteins that assist immune cells. They act via Opsonisation (sticking to pathogens to mark them), Chemotaxis (attracting phagocytes), or Lysis (forming a Membrane Attack Complex (MAC) causing the target cell to burst).

Physiological Responses

Fever: An elevated body temperature that inhibits pathogen survival and activates defensive proteins. However, prolonged fevers can damage host cells.
Inflammation: A response to injury and infection characterized by pain, redness, heat, and swelling. It consists of three steps:
1. Initiation: Pathogens enter; injured cells release cytokines; platelets wall off the area.
2. Vasodilation: Mast cells release histamine, causing blood vessels to widen and become more permeable.
3. Migration: Increased permeability allows phagocytes (neutrophils, macrophages) and complement proteins to enter the tissue. This results in the formation of pus (dead cells and pathogens) and subsequent tissue repair.

The Third Line of Defence (7D)

The adaptive immune system is specific and possesses immunological memory. It is initiated through antigen presentation by macrophages or dendritic cells.

Humoral Immunity

This response involves B lymphocytes and targets extracellular threats through antibodies.

B Lymphocytes: Originate and mature in the bone marrow and lymphoid tissues. There are two types: Plasma B cells (produce thousands of antibodies; short-lived) and Memory B cells (long-lived; provide future protection).
Antibodies: Also called Immunoglobulins (Ig). They consist of four polypeptide chains (two heavy, two light), forming a quaternary structure joined by disulphide bonds. They have a constant region (stem) and a variable region (antigen-binding sites).

The Four Steps of the Humoral Response

Selection of B Cell: A naive B cell interacts with a complementary antigen.
Selection of Helper T Cell: A T helper cell with a complementary receptor is selected and releases cytokines to stimulate the B cell.
Clonal Expansion and Differentiation: The B cell divides into many copies and differentiates into Plasma B cells and Memory B cells.
Production of Antibodies: Plasma cells secrete antibodies into the bloodstream.

Action of Antibodies

Neutralisation: Blocking pathogen sites used to attack host cells.
Agglutination: Form complex clumps of pathogens for easier phagocytosis.
Immobilisation: Restricting pathogen movement.
Opsonisation: Marking pathogens for destruction.
Activation of Complement: Facilitating MAC formation.

Cell-Mediated Immunity

This response focuses on intracellular threats (infected or abnormal cells) using T lymphocytes.

Helper T Cells: Release cytokines to activate both B and T cell responses.
Cytotoxic T Cells: Bind to MHC I markers on infected cells. Once activated, they release perforins and granzymes to induce apoptosis.
Memory T Cells: Provide faster responses to subsequent exposures.

Steps in Cell-Mediated Response

Antigen Presentation: Dendritic cells present antigens to naive T cells in lymph nodes.
Selection and Clonal Expansion: Active T helper cells release cytokines to stimulate the differentiation of naive T cells into Cytotoxic T cells.
Homing and Attack: Cytotoxic T cells travel to the site of infection, bind to the target cell's MHC I, and release molecules to kill it.

Haemolytic Disease of the Newborn (HDN)

HDN is an antibody-mediated condition. It occurs when an Rh-negative mother carries an Rh-positive foetus. During the birth of the first Rh-positive infant, foetal blood may leak into the mother's system. The mother's B cells recognize the Rh antigen as non-self and produce Anti-Rh (Anti-D) antibodies. During a second pregnancy with an Rh-positive foetus, these antibodies are small enough to cross the placenta and destroy the foetus's red blood cells, potentially leading to anaemia or death.

Allergic Reactions

Allergic reactions are immune responses to non-pathogenic allergens (e.g., hay fever, anaphylaxis). The process involves two phases:

Sensitisation: Initial exposure leads to B cell selection and differentiation. Plasma cells produce IgE antibodies, which bind to the surface of mast cells via their constant regions.
Re-exposure: Upon second exposure, the allergen binds to the IgE on the mast cells (cross-linking), causing the mast cells to degranulate and release histamine. This causes vasodilation, airway constriction, and increased capillary permeability. Symptoms of anaphylaxis include difficulty breathing, swelling, and vomiting.

The Lymphatic System (7E)

The lymphatic system acts as a transport network and a site for immune surveillance.

Primary Lymphoid Tissues: Include the Bone Marrow (where B and T cells are produced and B cells mature) and the Thymus (where T cells mature).
Secondary Lymphoid Tissues: Include the Lymph Nodes, Spleen, and Tonsils. These are sites where mature lymphocytes congregate. Lymph nodes filter foreign particles from lymph using fibers and allow APCs to meet B and T cells to initiate the adaptive immune response.

Questions & Discussion

Case Study: Thunderstorm Asthma

Question 4a (2019 Biology Exam): Pollen fragments cause allergic reactions when they interact with a specific type of cell and a protein of the immune system. Name the cell and the protein involved.

Response: The cell involved is the mast cell. The protein involved is the IgE antibody (immunoglobulin E).

Question 4b: List two strategies that a person could take to reduce their risk of developing thunderstorm asthma.

General recommendations: Avoid being outdoors during storms in high pollen seasons; use preventative asthma medication if prescribed.

Question 4c: Explain if it could be possible to develop a vaccine against thunderstorm asthma.

Response: Theoretical discussion involves the complexity of vaccines which typically target pathogens. A 'vaccine' for an allergy would need to desensitize the immune system to the allergen (pollen fragments) rather than attacking a living agent.