Overview of Innate Immunity from University of Portsmouth

UNIVERSITYOF PORTSMOUTH

METTE Overview of Innate Immunity

Learning Objectives

On completion of this session you should be able to

1. Identify and differentiate between the key components of the innate immune system.
2. Describe the cellular responses involved in innate immunity, including the activation and functions of key immune cells.

Overview of Innate Immunity

1. First line of defence against microbes
2. Exist before exposure to microbes
3. Found in plants, insect and vertebrates
4. 3 Essential functions
   1. Initial response to microbes
   2. Eliminate damaged cells and initiate the process of tissue repair
   3. Stimulate adaptive immune response
5. 2 types of responses
   1. Inflammation
   2. Anti-viral defence

Innate and Adaptive Immunity Attributes

TABLE 5-1 Innate and adaptive immunity

Attribute Innate immunity Adaptive immunity Response time Minutes/hours Days Specificity Specific for molecules and molecular patterns associated with pathogens and molecules produced by dead/damaged cells Highly specific; discriminates between even minor differences in molecular structure of microbial or nonmicrobial molecules Diversity A limited number of conserved, germ line- encoded receptors Highly diverse; a very large number of receptors arising from genetic recombination of receptor genes in each individual Memory responses Some (observed in invertebrate innate responses and mouse/human NK cells) Persistent memory, with faster response of greater magnitude on subsequent exposure Self/nonself discrimination Perfect; no microbe-specific self/nonself patterns in host Very good; occasional failures of discrimination result in autoimmune disease Soluble components of blood Many antimicrobial peptides, proteins, and other mediators Antibodies and cytokines Major cell types Phagocytes (monocytes, macrophages, neutrophils), natural killer (NK) cells, other leukocytes, epithelial and endothelial cells T cells, B cells, antigen-presenting cells Table 5-1 Kuby Immunology, Seventh Edition @ 2013 W. H. Freeman and Company

Components of Innate Immunity

Physical barriers to infection Chemical barriers to infection Pathogens Epithelial layers of skin and mucosal/glandular tissues Acidic pH and anti-microbial proteins and peptides H H +H H . Cellular responses to infection Damage/infection Pathogens Infected cell Macrophage Phagocytosis and degradation Killing by NK cell Dendritic cell Binding to cells Antibodies NK cell Activation of adaptive immune responses T-cell responses Cell'activation Anti-microbial substances (e.g., peptides, interferons) Cytokines and chemokines Systemic effects (e.g., fever) Pathogen elimination Inflammation: recruitment and activation of protective cells and molecules (e.g., complement) to the infection site

1. Anatomical barrier
   • Physical barriers
   • Chemical barriers
2. Cell
   • Phagocytic cells
   • Dendritic cell
   • NK cells, ILC
3. Soluble protein
   • Complement
   • Cytokines, chemokines
   • Antimicrobial substances

Kuby Immunology, 7th edition H+ H+

Anatomical Barriers - Physical

Skin and other Epithelial Barriers

Organ or tissue Innate mechanisms protecting skin/epithelium Skin Antimicrobial peptides, fatty acids in sebum Mouth and upper alimentary canal Enzymes, antimicrobial peptides, and sweeping of surface by directional flow of fluid toward stomach Stomach Low pH, digestive enzymes, antimicrobial peptides, fluid flow toward intestine Small intestine Digestive enzymes, antimicrobial peptides, fluid flow to large intestine Epithelial lining of alimentary canal Large intestine Normal intestinal flora compete with invading microbes, fluid/feces expelled from rectum Mammary glands Stomach Airway and lungs Cilia sweep mucus outward, coughing, sneezing expel mucus, macrophages in alveoli of lungs Large intestine Urogenital tract Flushing by urine, aggregation by urinary mucins; low pH, anti-microbial peptides, proteins in vaginal secretions Small intestine Salivary, lacrimal, and mammary glands Flushing by secretions; anti-microbial peptides and proteins in vaginal secretions Rectum Urogenital tract Figure 5-2 Kuby Immunology, Seventh Edition @ 2013 W. H. Freeman and Company Physical barriers to infection Chemical barriers to infection Pathogens Epithelial layers of skin and mucosal/glandular tissues H +H C Skin Lacrimal glands Mouth Salivary glands Airway Lung Epithelial lining of airway and lung H+ H Acidic pH and anti-microbial proteins and peptides H . H'· ·

Anatomical Barriers - Chemicals

TABLE 5-2 Some human antimicrobial proteins and peptides at epithelial surfaces

Proteins and peptides* Location Antimicrobial activities Lysozyme Mucosal/glandular secretions (e.g., tears, saliva, respiratory tract) Cleaves glycosidic bonds of peptidoglycans in cell walls of bacteria, leading to lysis Lactoferrin Mucosal/glandular secretions (e.g., milk, intestine mucus, nasal/respiratory and urogenital tracts) Binds and sequesters iron, limiting growth of bacteria and fungi; disrupts microbial membranes; limits infectivity of some viruses Secretory leukocyte protease inhibitor Skin, mucosal/glandular secretions (e.g., intestines, respiratory, and urogenital tracts, milk) Blocks epithelial infection by bacteria, fungi, viruses; antimicrobial S100 proteins, e.g .: - psoriasin Skin, mucosal/glandular secretions (e.g., tears, saliva/tongue, intestine, nasal/ respiratory and urogenital tracts) - Disrupts membranes, killing cells - calprotectin - Binds and sequesters divalent cations (e.g., manganese and zinc), limiting growth of bacteria and fungi Defensins (a and B) Skin, mucosal epithelia (e.g., mouth, intestine, nasal/respiratory tract, urogenital tract) Disrupt membranes of bacteria, fungi, protozoan parasites, and viruses; additional toxic effects intracellularly; kill cells and disable viruses Cathelicidin (LL37) ** Mucosal epithelia (e.g., respiratory tract, urogenital tract) Disrupts membranes of bacteria; additional toxic effects intracellularly; kills cells. Surfactant proteins SP-A, SP-D Secretions of respiratory tract, other mucosal epithelia Block bacterial surface components; promotes phagocytosis *Examples listed in this table are all produced by cells in the epithelia of mucosal and glandular tissues; examples of prominent epithelial sites are listed. Most proteins and peptides are produced constitutively at these sites, but their production can also be increased by microbial or inflammatory stimuli. Many are also produced con- stitutively in neutrophils and stored in granules. In addition, synthesis and secretion of many of these molecules may be induced by microbial components during innate immune responses by various myeloid leukocyte populations (monocytes, macrophages, dendritic cells, and mast cells). ** While some mammals have multiple cathelicidins, humans have only one. Kuby Immunology, 7th edition

Cellular Response to Infection

Cellular responses to infection

Damage/infection · NK cell Pathogens Infected cell Macrophage - Viral infected cell Phagocytosis - Malignancy degradation Killing by NK cell Dendritic cell Binding to cells Antibodies NK cell Activation of adaptive immune responses T-cell responses Cell'activation Cytokines and chemokines Inflammation: Systemic effects (e.g., fever) Pathogen elimination activation of protective cells and molecules (e.g., complement) to the infection site

1. Phagocytic cells
   • Macrophage, neutrophil "Phagocytosis"
2. Dendritic cell
   • -> activate adaptive immune response

Anti-microbial substances (e.g., peptides, interferons)

Cellular Response Mechanisms

Phagocytes (neutrophils, dendritic cells, macrophages) Pathogen-associated molecular patterns (PAMPs) PAMPs recognized by pattern recognition receptors (PRRs) Pathogen killed and degraded in lysosomes Antimicrobial peptides Pathogen Phagocyte activated to produce anti-microbial components, followed by secretion of inflammation- promoting cytokines and chemokines C-reactive protein (CRP) SP-A, SP-D, Mannose- binding lectin (MBL) Complement proteins Phagocytosis Membrane damage kills pathogen The immune system

1. Detects/senses the presence of a pathogen
2. Mounts a response Opsonins are recognized by opsonin receptors, enhancing phagocytosis Opsonized pathogen Innate initiation of adaptive response CRP, MBL, complement proteins activate complement pathway . Dendritic cell PRRs recognize PAMPs, activating phagocytosis and signaling pathways. Complement destroys membrane, stimulates inflammation, attracts neutrophils and other cells " Dendritic cells migrate to lymph nodes, carrying intact or degraded pathogens. Antigen fragments bound to cell surface MHC proteins are T cell . recognized by T cells. Activated T cells initiate adaptive responses. Figure 5-6 Kuby Immunology, Seventh Edition @ 2013 W. H. Freeman and Company ‘060

Summary of Innate Immunity

1. The main components of the innate immune system include physical and chemical barriers.
2. Cellular responses involve cells reacting to signals from their environment, crucial for maintaining balance in multicellular organisms.
3. Cells involved include macrophages, neutrophils, natural killer (NK) cells and dendritic cells.
4. Activation of these cells triggers inflammation and enhances antiviral defense mechanisms.I KNIVEDOITV .-

UNIVERSITYOF PORTSMOUTH

METTE Innate Immunity - Recognition of Pathogens

Learning Objectives

On completion of this session you should be able - to understand the mechanisms underlying the recognition of pathogens and dead cells by the immune system, including the role of pattern recognition receptors (PRRs) and the consequences of this recognition.

Recognition of Pathogens & Dead Cells

1. The innate response recognises components of microbes that cannot or do not easily change (required for survival and/or infectivity)
2. These are also shared by many classes of microbe
3. Examples: dsRNA, lipopolysaccharide (LPS), lipoteichoic acid (LTA), peptidoglycan, N-formylated-Met peptides, mannose glycans
4. Termed pathogen associated molecular patterns (PAMPs)