Antigens and Pathogens Notes

Antigens and the Immune System

Overview

• The immune system protects the body from foreign substances called pathogens.

• Key components include immune cells (leukocytes or white blood cells) like eosinophils, neutrophils, and lymphocytes.

• Antibodies (immunoglobulins) are proteins produced by B lymphocytes that bind to specific antigens.

8.1 Antigens and Pathogens

Nature of Antigens

• Antigens are unique molecules that elicit an immune response.

• They can be self-antigens or non-self antigens.

• Immune cells differentiate between self and non-self antigens.

Definition

• Antigens are molecules recognized by receptors on T lymphocytes (T cells) or antibodies produced by B lymphocytes (B cells).

• Antibodies (immunoglobulins, Ig) can be bound to or secreted by B lymphocytes.

Importance

• Antigens enable the body to recognize and respond to potentially harmful pathogens.

• Immunogens are antigens that elicit an immune response; the term "antigen" is commonly used.

Structure of Antigens

• Most antigens are protein-based (one or more polypeptide chains).

• Can also be composed of carbohydrates, lipids, or nucleic acids.

• Example: ABO blood group carbohydrates are antigens.

Types of Antigens

• Expressed on the surface of the plasma membrane of cells.

• Some antigens (e.g., bacterial toxins) circulate freely in body fluids.

• Allergens cause immediate hypersensitivity reactions (allergic responses).

  • These are rapid, vigorous overreactions to harmless antigens.

  • Examples: pollen, fur, house dust, latex, foods (peanuts, lobster, MSG).

  • Reactions range from mild to life-threatening anaphylaxis.

Self vs. Non-Self Antigens

• The immune system distinguishes between self-antigens (own cells) and non-self antigens (foreign).

Case Study: Blood Groups and Transfusions

Historical Context

• First successful human-to-human blood transfusion in the 1800s.

• Early transfusions were risky due to the lack of knowledge about blood groups.

• ABO blood groups discovered in 1901; matching transfusions suggested in 1907.

ABO Blood Type Antigens

• A and B antigens consist of carbohydrate molecules attached to proteins and lipids on red blood cell membranes.

• Differences in carbohydrate structure distinguish A and B antigens.

• Transfusing mismatched blood elicits an immune response.

Immune Response to Mismatched Blood

• Antibodies recognize the transfused blood cells as foreign.

• This leads to agglutination (clumping) of red blood cells.

• Agglutination destroys red blood cells, causing severe anemia and potentially death.

Blood Group Determination

• Presence or absence of A and B antigens determines blood type (A, B, AB, or O).

• Group O blood has neither A nor B antigens.

Blood Group Matching

• Blood group matching is a quick procedure.

• Antibodies (anti-A, anti-B) are mixed with the patient's blood to identify blood group.

• Matching antibody and antigen are never found in the same individual; mixing causes agglutination.

Case Study: Allergic Responses

Allergic Rhinitis (Hay Fever)

• Allergic reaction to pollen.

• Pollen particles carry allergenic antigens.

• Grass and tree pollens are common causes in Australia and New Zealand.

• Seasonal pattern: most abundant in spring and early summer.

Mast Cell Activation and Histamine Release

• Mast cell release of histamine is central to immediate hypersensitivity reactions.

• Allergic responses are mediated by immunoglobulin E (IgE).

• IgE is produced by plasma cells and travels in the bloodstream.

• IgE binds to receptors on mast cells (common in epithelial and mucosal tissues).

Mechanism of Allergic Response

1. Initial exposure to allergens triggers plasma cells to produce IgE.

2. IgE binds to mast cells.

3. Subsequent exposure to the same allergen crosslinks two IgE molecules on a mast cell.

4. This triggers a cascade of signaling molecules, causing mast cells to release histamine.

Effects of Histamine

• Histamine binds to receptors on various cell types, causing:

  • Blood vessel dilation.

  • Decrease in blood pressure.

  • Increased blood vessel permeability to immune cells and fluids.

  • Contraction of smooth muscles in airways (difficulty breathing).

  • Activation of fluid-secreting cells (runny nose, teary eyes, sneezing).

Responding to Antigens

Antigen Recognition

• Antigen recognition depends on receptors.

  • B lymphocytes: membrane-bound antibodies recognize free antigens or antigens on pathogens.

  • These antibodies can also be secreted.

  • T lymphocytes: receptors recognize antigens presented by antigen-presenting cells (APCs).

Major Histocompatibility Complex (MHC) Proteins

• MHC proteins (also called human leukocyte antigens, HLA) present self or non-self antigens to T lymphocytes.

• Different classes of MHC proteins exist.

T Lymphocyte Maturation in the Thymus

• Positive Selection: T lymphocytes that do not interact with MHC proteins are destroyed (apoptosis).

• Negative Selection: T lymphocytes that react with self-antigens in the thymus bind tightly and die (clonal deletion).

• Clonal deletion is a two-stage process: selecting T lymphocytes that can recognize MHC proteins and eliminating those that react to self-antigens.

Tolerance

• Tolerance (self-tolerance) is the inability to respond to self-antigens.

• Breakdown of self-tolerance leads to autoimmune diseases.

Immunogens

• Not all antigens elicit an immune response; those that do are called immunogens.

Pathogens as Sources of Non-Self Antigens

Pathogens

• Pathogens are agents that cause disease.

  • Primary pathogens: cause disease any time they are present.

  • Opportunistic pathogens: cause disease when host defenses are weakened.

• Most pathogens contain unique antigens recognized by the immune system.

• Examples: tuberculosis bacterium, tinea fungus, influenza virus.

• Toxins secreted by pathogens can also act as antigens.

Cellular Pathogens

• Cellular pathogens of plants and animals include:

  • Bacteria

  • Fungi

  • Oomycetes

  • Protozoans

  • Worms

  • Arthropods

Bacteria

• Prokaryotes; exposure to pathogenic bacteria is common.

• Pathogenic bacteria have evolved strategies to avoid immune recognition or interfere with the immune response.

  • Examples: inhibiting antigen processing, impairing MHC synthesis, disrupting lymphocyte activation.

• Not all bacteria are pathogenic; the human body relies on some bacteria for metabolic products.

  • Example: Escherichia coli in the intestine.

  • However, the same strain can cause infection if it enters the urinary tract.

Fungi

• Diverse family: macroscopic (mushrooms) to microscopic (molds, yeasts).

• Secrete digestive enzymes to break down organic matter, which can cause disease.

• Fungal cells produce surface glycoproteins and polysaccharides that act as antigens.

Oomycetes

• Cause blight and downy mildew in plants and life-threatening infections in animals.

• Classified in kingdom Protista; once thought of as fungi.

• Oomycetes have:

  • Motile cells (flagella)

  • Walls of cellulose

  • Many unique cellular processes compared to fungi.

• Release molecules that suppress the host's immune response and inhibit apoptosis.

• Example: Phytophthora cinnamomi, which destroys eucalypt timberland in Australia.

Protozoans

• Unicellular eukaryotes.

• Some reproduce within host cells; others reproduce extracellularly.

• Life cycles may include multiple stages in different hosts.

• Surface antigens change (antigenic variation) to evade detection by the host.

Worms

• Parasitic worms infect plants and animals: flatworms (tapeworms) and roundworms (hookworms, pinworms).

• In plants, roundworms infect roots.

• In animals, parasitic worms regulate the immune system to suppress the immune response against them.

  • Example: Nippostrongylus brasiliensis secretes inhibitors of antigen presentation.

Arthropods

• Invertebrates with external skeletons: insects (mosquitoes, ticks, lice, mites).

• Arthropod saliva contains molecules that modulate the host immune response and inhibit inflammation.

• Arthropod saliva contains antigens that can trigger an immune response, used in vaccine development.

• Some arthropods damage plants; e.g., psyllids (lerp insects) induce gall formation on leaves.

Non-Cellular Pathogens

• Viruses, viroids, and prions are non-cellular pathogens.

Viruses

• Infectious agents composed of genetic material (DNA or RNA) enclosed in a protein coat; some have a lipoprotein envelope.

• Antigenic Drift: Gradual accumulation of genetic mutations, leading to similar but not identical viruses recognized by the immune system.

• Antigenic Shift: Abrupt change in the genetic code due to re-assortment of genes from different viral strains, resulting in significantly different antigens.

Viroids

• Self-cleaving RNA enzymes (ribozymes); short, circular strands of RNA lacking a protein coat.

• Only known to be pathogens of plants.

• Damage plants by competing for nucleotides and forming viroid bundles.

• High mutation rate leads to antigenic variation.

Prions

• Infectious agents that do not contain genetic material; proteins with an abnormal shape.

• Prions stimulate normal cellular prion proteins (PrP) to misfold into the infectious prion form.

• Resistant to being denatured or broken down by proteases.

• Cause neurodegenerative diseases in mammals.

  • Examples: Scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE or mad cow disease) in cattle.

• Prions do not trigger an immune response because they are similar to normal PrP, and T lymphocytes that would have responded to normal PrP would have been destroyed to prevent an autoimmune reaction.

• Another reason could be that prions cannot be broken down and presented by antigen-presenting cells.

Case Study: Pioneering Studies of Disease

Louis Pasteur

• Established the existence of microorganisms and showed that infectious diseases were caused by microbes.

• Prior to this, post-operative infections in hospitals were common, exacerbated by practices such as doctors performing post-mortems and then surgery without changing clothes.

Joseph Lister

• Observed that wounds left open to the air were more prone to infection.

• Concluded that infection was due to 'something in the air'.

• Used carbolic acid (poisonous to living organisms) in hospital wards to kill 'invisible microbes', dramatically reducing infection rates.

• This was the first practice of antiseptic surgery.

Robert Koch

• Studied anthrax and formulated Koch's postulates to establish whether a specific microorganism was the cause of a particular disease.

• Koch's Postulates:

  1. The microorganism must be present in the tissues of the infected organism and not in a healthy organism.

  2. The microorganism must be able to be cultivated in isolation from the infected organism.

  3. When an uninfected organism is then inoculated with the culture, it should develop symptoms of the disease.

  4. Samples from the second infected organism should be able to be isolated and found to be the same as the microorganism from the first infected organism.