Responding to Antigens and Innate Immunity

Antigens and Pathogens

• Antigens: Unique molecules that elicit an immune response, crucial for immunity.
  • Can be self or non-self antigens.
  • Immune cells differentiate between self and non-self antigens.

Nature of Antigens

• Recognized by receptors on T lymphocytes (T cells) or antibodies from B lymphocytes (B cells).
• Antibodies (immunoglobulins - Ig) can be bound to or secreted by B lymphocytes.
• Important for recognizing harmful pathogens and mounting an immune response.
• Immunogens: Antigens that elicit an immune response.

Structure of Antigens

• Most are protein-based (one or more polypeptide chains).
• Can also be carbohydrates, lipids, or nucleic acids (e.g., ABO blood group carbohydrates).

Types of Antigens

• Expressed on the surface of the plasma membrane as recognition sites.
• Some antigens (e.g., bacterial toxins) circulate freely in body fluids.
• Allergens: Antigens causing immediate hypersensitivity reactions (allergic responses).
  • Allergic responses 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.
• Immune system distinguishes between self and non-self antigens.

Blood Groups and Transfusions

• First successful human-to-human blood transfusion occurred in the 1800s.
• ABO blood groups discovered in 1901; matching transfusions suggested in 1907.
• A and B blood type antigens are carbohydrate molecules on red blood cell membranes.
• Structure of carbohydrate differs between A and B antigens.
• Transfusing the wrong blood type elicits an immune response.
• Agglutination (clumping) of red blood cells occurs when antibodies recognize foreign blood cells.
• Agglutination destroys red blood cells, leading to severe anemia or death.
• Presence or absence of A and B antigens determines blood group (A, B, AB, or O).
• Group O blood has neither A nor B antigens.
• Blood group matching is a quick procedure using antibodies (anti-A and anti-B).
• Matching antibody and antigen are never found in the same individual; mixing causes agglutination.

Allergic Responses

• Allergic rhinitis (hay fever) is an allergic response to pollen.
• Pollen carries allergenic antigens.
• Grass and tree pollens are common causes in Australia and New Zealand.
• Pollen sensitivity has a seasonal pattern (spring/early summer).
• Mast cell release of histamine is central to immediate hypersensitivity reactions.
• Allergic responses are mediated by immunoglobulin E (IgE) antibodies.
• IgE is produced by plasma cells and binds to mast cells in epithelial and mucosal tissues.
• Subsequent exposure to the same allergen causes it to bind to adjacent IgE molecules, crosslinking them.
• This triggers a cascade, causing mast cells to release histamine (and other mediators) by exocytosis.
• Histamine binds to receptors on various cell types, causing:
  • Blood vessel dilation.
  • Decrease in blood pressure.
  • Increased permeability of blood vessels.
  • Contraction of smooth muscles (airways).
  • Activation of fluid-secreting cells (runny nose, teary eyes, sneezing).

Responding to Antigens

• Antigen recognition relies on receptors.

  • B lymphocyte receptors are membrane-bound antibodies that recognize free or pathogen-surface antigens.
  • Antibodies can also be secreted by B lymphocytes.
  • T lymphocyte receptors recognize antigens presented by antigen-presenting cells (APCs).

• Many different receptors exist, specific to particular antigens.

• Major histocompatibility complex (MHC) proteins / Human leukocyte antigens (HLA): Proteins on cell surfaces that present self or non-self antigens to T lymphocytes.

• During T lymphocyte maturation in the thymus:

  • Positive selection: T lymphocytes that do not interact with MHC proteins are destroyed via apoptosis.
  • Negative selection: T lymphocytes that react with self-antigens in the thymus die.
  • This two-stage process (clonal deletion) selects T lymphocytes that recognize MHC proteins and eliminates those reacting to self-antigens.

• Tolerance (self-tolerance): Inability to respond to self-antigens.

• Breakdown of self-tolerance leads to autoimmune diseases.

• Immunogens elicit an immune response.

Pathogens as Sources of Non-Self Antigens

• Pathogens: Agents causing disease.
  • Primary pathogens: Cause disease any time they are present.
  • Opportunistic pathogens: Cause disease when host defenses are weakened.
• Most pathogens have unique antigens recognized by the immune system.
• Toxins secreted by pathogens can also act as antigens.

Cellular Pathogens

• Cellular pathogens include bacteria, fungi, oomycetes, protozoans, worms, and arthropods.

Bacteria

• Prokaryotes, exposure to pathogenic bacteria is common.
• Many have evolved ways to avoid recognition or interfere with immune response (e.g., inhibiting antigen processing, impairing MHC synthesis, disrupting lymphocyte activation).
• Not all bacteria are pathogenic; some are beneficial (e.g., Escherichia coli in the intestine).
• Same strain of $E. coli$ can be beneficial in the intestine but cause infection in the urinary tract.

Fungi

• Diverse family, from macroscopic mushrooms to microscopic molds and yeasts.
• Secrete digestive enzymes to break down organic matter; these secretions often cause disease.
• Fungal cells produce surface glycoproteins and polysaccharides that act as antigens.

Oomycetes

• Cause blight and downy mildew on plants and infections in animals.
• Originally thought of as fungi, now classified in kingdom Protista.
• Have motile cells (flagella), cellulose walls, and unique cellular processes.
• Release molecules that suppress host's immune response and inhibit apoptosis.
• Example: Phytophthora cinnamomi destroys eucalypt timberland in Australia.
• Spores attracted to roots by chemical signals.

Protozoans

• Unicellular eukaryotes.
• Some reproduce within host cells, others extracellularly (e.g., Giardia lamblia).
• Life cycles include multiple stages in different hosts.
• Antigenic variation: Express different surface proteins (antigens) at different life stages to evade detection.

Worms

• Parasitic worms infect plants and animals (e.g., tapeworms, hookworms, pinworms).
• In plants, roundworms infect roots.
• In animals, they suppress immune response (e.g., Nippostrongylus brasiliensis secretes inhibitors of antigen presentation).

Arthropods

• Invertebrates with external skeletons (exoskeletons).
• Transmit or cause disease in humans (e.g., mosquitoes, ticks, lice, mites).
• Saliva contains molecules that modulate host immune response and inhibit inflammation.
• Saliva also contains antigens that can trigger an immune response (used in vaccine development).
• Saliva from feeding psyllids kills leaf tissue in plants.

Non-Cellular Pathogens

• Viruses, viroids, and prions.

Viruses

• Infectious agents composed of genetic material (DNA or RNA) in a protein coat.
• Some have a lipoprotein envelope.
• Antigenic drift: Gradual accumulation of genetic mutations causing changes to viral antigens (recognized by immune system if similar virus infected before).
• Antigenic shift: Abrupt change in genetic code due to re-assortment of genes from different viral strains, resulting in significantly different antigens.

Viroids

• Self-cleaving RNA enzymes (ribozymes) that lack a protein coat.
• Only pathogens of plants.
• Damage plants by competing for nucleotides and forming viroid bundles.
• High mutation rate leads to antigenic variation, avoiding host resistance.

Prions

• Infectious agents that do not contain genetic material.
• Proteins similar to normal cellular prion proteins (PrP) but with an abnormal shape.
• Stimulate normal PrP to misfold into infectious form.
• Resistant to denaturation and proteases.
• Cause neurodegenerative diseases in mammals (e.g., scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle).
• CJD causes vacuoles and misfolded proteins (plaques) in the brain, killing neurons.
• Prions do not trigger an immune response because they are similar to normal PrP, and T lymphocytes that respond to normal PrP are destroyed. Also, prions may not be processed and presented by antigen-presenting cells.

Pioneering Studies of Disease

• Louis Pasteur established the existence of microorganisms and showed that infectious diseases were caused by microbes.
• Joseph Lister introduced antiseptic surgery using carbolic acid to kill 'invisible microbes'.
• Robert Koch studied anthrax and formulated Koch's postulates to establish whether a specific microorganism was the cause of a particular disease:
  1. The microorganism must be present in the tissues of the infected organism but 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.

Innate Immunity

• Immune systems respond to non-self antigens and defend against pathogens through various mechanisms.
• These include barriers and immune responses to pathogens that breach them.
• In vertebrates, immune responses are divided into innate (non-specific) and adaptive (specific) responses.

Barriers to Infection

• First-line defenses providing innate resistance:
  • Physical barriers (skin, bark).
  • Chemical barriers (lysozyme enzymes).
  • Microbiological barriers (microbiota/microflora).

Physical Barriers in Plants

• Cell walls provide strength and flexibility.
• Cutin and waxes form the cuticle on the outer cell wall.
• Thicker cuticle and bark prevent more pathogens from infecting.
• Stomata create openings but can be closed when signaled.
• Vertical leaf orientation prevents water collection.

Physical Barriers in Animals

• Epithelial cells line skin and respiratory/gastrointestinal/urogenital tracts, forming a continuous barrier.
• Toughened skin, mucus-secreting membranes, and cilia-lined membranes trap and sweep away foreign bodies.

Chemical Barriers in Plants

• Chemicals defend against infection when physical barriers are breached; levels increase upon pathogen attack.
  • Alkaloids: Toxic to many organisms (e.g., caffeine, nicotine, morphine, capsaicin, atropine).
  • Cyanogenic glycosides: Break down to form hydrogen cyanide, disrupting ATP production in eukaryotic cells.
  • Phenolics: Include phytoalexins, flavonoids, and tannins; have antibiotic properties, disrupt metabolism, and bind to digestive enzymes.
  • Saponins: Soap-like properties; disrupt lipids and plasma membranes.
  • Terpenes: Make up essential oils; pyrethrins are insecticides, phytoectysones disrupt insect moulting.

Chemical Barriers in Animals

• External barriers include lysozyme enzymes and toxic metabolites (lactic acid, fatty acids) in tears, sweat, and saliva.
• Stomach acid and digestive enzymes kill many pathogens.
• Lung fluid contains proteins (surfactants) that coat pathogens, aiding macrophage elimination.
• Genital mucosa produce secretions for defense against pathogens.

Microbiological Barriers in Animals

• Non-pathogenic bacteria (normal flora) on skin, mouth, nose, throat, gastrointestinal tract, and urogenital tract.
• Prevent growth of pathogens by competing for space/resources and producing chemicals that lower pH.
• Antibiotics can disrupt normal flora, predisposing to infections.
• In weakened immune systems, normal flora can grow unchecked and cause disease.

Innate Immune Response

• Attacking cells and molecules immediately meet pathogens that breach barriers.
• Found in all organisms.
• Critical for controlling infections until adaptive immune response develops.

Innate Immune Responses in Vertebrates

• Non-specific, rapid, present in all animals, fixed responses, no immunological memory.

Innate Immune Responses in Plants

• Mainly chemical response.
• Triggered when plant cells recognize pathogen-associated molecular patterns (PAMPs).
• Recognized by pattern recognition receptors (PRRs).
• Resistance genes: Code for proteins (R proteins) that switch on defenses when they recognize specific PAMPs (avirulence proteins AVr).
• Plants use hormone-like chemicals (jasmonic acid, salicylic acid) to activate responses.
• Defenses are activated, including increased toxin production and strengthening of cell walls.

Proteins Produced by Plant Tissues

• Defensins: Small proteins acting against digestive enzymes and microbes by disrupting plasma membranes.

• Protease inhibitors: Inhibit enzymes such as trypsin.

• Digestive enzyme inhibitors: Block normal digestion; include lectins and ricin.

• Hydrolytic enzymes: Break down cell walls; chitinases, glucanases, lysozymes.

• Pathogen recognition activates enzymes that strengthen cell walls.

• Cell-mediated responses (hypersensitive response) can result in self-destruction of infected tissues.

Innate Immune Responses in Animals

• Recognize and respond to pathogens through identification of PAMPs (lipopolysaccharide, peptidoglycan, flagellin, microbial nucleic acids).
• White blood cells (leukocytes) have pattern recognition receptors (PRRs) on their surface to recognize PAMPs.