Innate Immunity Flashcards

Innate Immunity

Overview

The immune system defends against pathogens through various mechanisms:

• Barriers prevent infection.
• Immune responses occur when pathogens breach these barriers.
• In vertebrates, there are innate (non-specific) and adaptive (specific) immune responses. Adaptive immunity is covered in Chapter 9.

Barriers to Infection

First-line defenses provide innate resistance:

• Physical barriers: Skin or bark.
• Chemical barriers: Lysozyme in saliva.
• Microbiological barriers: Microbiota (microflora).

Physical Barriers in Plants

• Cell walls provide strength and flexibility.
• Cuticle: Made of cutin and waxes; a thicker cuticle prevents more infections.
• Bark: A thicker layer prevents pathogen entry in trees.
• Stomata: Openings for pathogens, but can close when signaled (Figure 8.2.2).
• Leaf Orientation: Vertical leaves prevent water collection, which inhibits water-reliant pathogens.

Physical Barriers in Animals

• Epithelial cells line the skin, respiratory, gastrointestinal, and urogenital tracts.
• They are joined tightly by membrane proteins to form a continuous barrier.
• Adaptations:
  • Keratinized skin.
  • Mucus-secreting membranes trap organisms.
  • Cilia sweep foreign bodies away (Figure 8.2.3).

Chemical Barriers

Chemical Barriers in Plants

Plants produce chemicals that defend against infection after physical barriers are breached. Levels may increase upon pathogen attack.

• Alkaloids: Toxic to fungi, bacteria, insects, and humans (e.g., caffeine, nicotine, morphine, capsaicin, atropine). Toxicity is dose-dependent. Atropine is a cardiac stimulant in small doses but lethal in large doses.
• Cyanogenic Glycosides: Break down to form hydrogen cyanide, which is toxic to eukaryotic cells because it disrupts ATP production in mitochondria by blocking the electron transfer chain.
• Phenolics:
  • Phytoalexins and Flavonoids: Antibiotic properties that disrupt cellular metabolism.
  • Tannins: Water-soluble, stored in vacuoles, toxic to pathogens. Bind to salivary proteins and digestive enzymes like trypsin, leading to pathogen death from inadequate energy. Effective against antibiotic-resistant bacteria.
• Saponins: Soap-like properties that break down lipids and disrupt plasma membranes.
• Terpenes: Essential oils; pyrethrins are used in insecticides. Phytoectysones mimic insect moulting hormones, disrupting larval development.

Chemical Barriers in Animals

• External Chemical Barriers: Lysozyme enzymes, lactic acid, and fatty acids in tears, sweat, and saliva provide generalized defense by destroying bacterial cell walls (Figure 8.2.4).
• Other Chemical Barriers:
  • Stomach acid and digestive enzymes kill pathogens.
  • Lung fluid contains surfactants that coat pathogens, aiding macrophage elimination.
  • Genital mucosa produce secretions for defense.

Microbiological Barriers in Animals

• Normal flora (non-pathogenic bacteria) are present on skin, in the mouth, nose, throat, gastrointestinal tract, and urogenital tract.
• They prevent pathogen colonization by competing for space and resources and by producing chemicals that lower pH.
• Antibiotics can disrupt normal flora, predisposing individuals to infections.
• In immunocompromised individuals, normal flora can cause disease.

The Innate Immune Response

• Attacking cells and molecules immediately respond if pathogens breach barriers.
• Found in all organisms, indicating its fundamental importance.
• Keeps infections under control until the adaptive immune response develops (which can take several days).

Innate Immune Responses in Vertebrates:

• Non-specific: Do not target specific antigens.
• Rapid: Occur within hours.
• Present in all animals.
• Fixed responses: Do not adapt.
• Do not result in immunological memory.

Innate Immune Responses in Plants

• Mainly a chemical response.
• Some chemicals are always present, while others are produced upon pathogen exposure.
• Triggered by pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides.
• Recognized by pattern recognition receptors (PRRs).
• Resistance Genes: Code for R proteins that activate defenses upon PAMP recognition.
• Specific pathogen molecules are avirulence proteins (AVr), coded by AVr genes.
• Hormone-like chemicals like jasmonic acid and salicylic acid activate responses (Figure 8.2.5).

Plant Defense Proteins and Enzymes

• Plants produce proteins and enzymes when under attack.
  • Defensins: Small proteins that act against digestive enzymes and disrupt pathogen plasma membranes; rich in cysteine (Figure 8.2.6).
  • Protease Inhibitors: Inhibit digestive enzymes like trypsin.
  • Digestive Enzyme Inhibitors: Block normal digestion, including lectins (block starch digestion) and ricin (highly toxic; 0.2 mg can kill an adult).
  • Hydrolytic Enzymes: Break down cell walls:
    • Chitinases: Break down chitin in fungal cell walls and insect exoskeletons.
    • Glucanases: Break down glucans in oomycete cell walls.
    • Lysozymes: Digest bacterial cell walls.
• Pathogen recognition may activate enzymes that strengthen cell walls.
• Hypersensitive Response: Self-destruction of infected tissues to wall off the pathogen.

Innate Immune Responses in Animals

• Animals recognize and respond to pathogens via PAMPs:
  • Lipopolysaccharide (Gram-negative bacteria).
  • Peptidoglycan (Gram-positive bacteria).
  • Flagellin.
  • Microbial nucleic acids.
• Leukocytes (white blood cells) have PRRs on their surface to recognize PAMPs.

Pattern Recognition Receptors (PRRs)

Five main classes (Table 8.2.1):

• Toll-like receptors (TLRs)
• C-type lectin receptors (CLRs)
• NOD-like receptors (NLRs)
• RIG-like receptors (RLRs)
• AIM2-like receptors (ALRs)

PRR location determines whether they respond to intracellular or extracellular pathogens.
The innate immune response to PAMPs is non-specific, unlike the adaptive immune response.

Granulocytes

Leukocytes containing cytoplasmic granules that are released during immune responses. Neutrophils, basophils, eosinophils, and mast cells are granulocytes.

• Basophils and mast cells release histamine and are involved in allergic responses.
• High numbers of eosinophils are associated with parasitic infections.
• Granulocytes in blood are identified by granule staining: basophils (blue), eosinophils (red), neutrophils (neutral pink) (Table 8.2.2).

Phagocytes

Leukocytes that engulf and break down pathogens via phagocytosis (Figure 8.2.7). Include neutrophils, macrophages, monocytes, and dendritic cells.

Antigen Presentation

Macrophages and dendritic cells act as antigen-presenting cells (APCs). They present antigen fragments linked to MHC-II proteins on their surface (Figure 8.2.8).

• MHC Class I (MHC-I): Found on all nucleated cells; present peptide antigens to cytotoxic T cells. Intracellular pathogens down-regulate MHC-I expression to avoid recognition.
• Natural Killer (NK) Cells: Recognize the absence of MHC-I in infected cells and release molecules that destroy the cell (Figure 8.2.9).
• MHC Class II (MHC-II): Found on APCs; activate helper T cells, linking innate and adaptive immune responses (Figure 8.2.10).

Summary of Innate Immune Cells

Table 8.2.2 summarizes leukocytes involved in innate immune responses, indicating their roles in phagocytosis, antigen presentation, and cytokine release.

Defensive Molecules

Complement proteins and cytokines are involved in both innate and adaptive immune responses.

Complement Proteins

• Over 30 proteins circulate in the blood and help kill foreign cells.
• Activated by antigens and carbohydrates on bacterial and parasite surfaces.
• Activation leads to lysis of pathogens by punching holes in plasma membranes.
• Attract phagocytes to the infection site.
• Also involved in adaptive immune responses via antigen-antibody complexes.

Cytokines

• Small signaling molecules that coordinate immune responses.
• Peptides, proteins, or glycoproteins released by body cells in response to cell damage or pathogens.
• Promote lymphocyte proliferation, induce inflammation and fever, promote antibody responses, and activate macrophages.

Interferons

• Produced by and act on virus-infected host cells (autocrine manner).
• Activate cells to break down viral RNA and block translation, limiting viral replication.
• Attract NK cells, which kill virus-infected cells.
• Non-specific; act against any virus, but viruses vary in susceptibility.
• Some viruses evade interferon-induced defenses or inhibit interferon production.
• Also play a smaller role in combating bacterial and parasitic infections.

Chemokines

• Type of cytokine that acts as a chemical attractant (chemo-attractant).
• Attract leukocytes to sites of infection and inflammation.

The Inflammatory Response

• Accumulation of fluid, plasma proteins, and leukocytes at damaged or infected tissue.
• Results in heat, pain, swelling, redness, and loss of function.
• Triggered by interaction between leukocytes and pathogens, leading to the production, activation, or release of peptides and proteins like complement proteins and cytokines.
• Acute inflammation involves phagocytes and occurs soon after infection.
• Inflammation can also involve lymphocytes and occur later as part of the adaptive immune response.

Steps in Acute Inflammatory Response (Figure 8.2.11):

1. Pathogens breach barriers.
2. Injured cells release cytokines (chemokines), attracting neutrophils. Mast cells release histamine, increasing blood vessel dilation and permeability. Platelets release clotting factors.
3. Neutrophils migrate towards cytokines and are activated, recruiting macrophages and secreting factors that degrade and kill pathogens.
4. Macrophages are activated and secrete cytokines, phagocytosing pathogens and debris. This leads to pus formation (leukocytes, dead pathogens, and cell debris).
5. Inflammatory response continues until the pathogen is eliminated and the wound is healed.

Fever

• Increase in body temperature caused by inflammatory cytokines resetting the hypothalamus.
• Normal human body temperature is around 37°C.
• Fever slows replication of bacteria and viruses by shifting temperature away from their optimal range.
• Increases activity and proliferation of leukocytes, improving the immune response.