Question

Some pathogens proliferate within extracellular tissue spaces. Other proliferate within cells. Describe 4 examples of how the innate immune system deals with intracellular infections, and 4 examples how innate immune system deals with extracellular infections.

4 Marks.

Answer 1

Answer;

4 examples of how the innate immune system deals with intracellular infections, and 4 examples how innate immune system deals with extracellular infections;

The innate immune response is present in its final state from birth and attempts to defend against all pathogens.

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Innate immunity is comprised of different components including physical barriers (tight junctions in the skin, epithelial and mucous membrane surfaces, mucus itself); anatomical barriers; epithelial and phagocytic cell enzymes (i.e., lysozyme), phagocytes (i.e., neutrophils, monocytes, macrophages), inflammation-related serum proteins (e.g., complement, C-reactive protein, lectins such as mannose-binding lectin, and ficolins); surface and phagocyte granule antimicrobial peptides (e.g., defensins, cathelicidin, etc.); cell receptors that sense microorganisms and signal a defensive response (e.g., Toll-like receptors); and cells that release cytokines and inflammatory mediators (i.e., macrophages, mast cells, natural-killer cells). Once the interaction host-invader pathogen enters, a signaling cascade is initiated which enhances the immune response and activates specific mechanisms (3-5). This natural immune response is designed to: a) prevent infection, b) eliminate invader pathogens, and c) stimulate the acquired immune response.

Components of the innate immune system

The innate immune system includes physical and anatomical barriers as well as effector cells, antimicrobial peptides, soluble mediators, and cell receptors (Table 1). Skin and mucosa provide an effective immune barrier between the internal and external environment. Skin acts as not only a physical barrier but also a chemical shield. The most external layer of epidermis mainly consists of keratinocytes, which are tightly linked by desmosomes and embedded in a layer of extracellular matrix proteins. Keratinocytes not only act as a physical barrier but also express pattern recognition receptors (PRRs) and are capable of producing cytokines and antimicrobial peptides that, in turn, induce an inflammatory cascade and microbial destruction respectively (6,7). Furthermore, sebaceous glands associated with hair follicles produce large amounts of fatty acids which create an acidic environment that is hostile to microorganisms. Mucous membranes in the digestive, respiratory, and genitourinary tracts have a continuous epithelium that prevents microorganisms from entering the host. In addition, these epithelial cells produce antimicrobial peptides such as defensins. The production of defensins is also enhanced by the action of inflammatory cytokines including interleukin (IL)-1 and tumor necrosis factor alpha (TNF-α) which are produced by macrophages and other immune cells in response to invading pathogens .

COMPONENT	FUNCTION
Barriers
Skin	Prevents microbial entrance
Mucosa	Prevents microbial entrance, secretes proteins and enzymes, absorbs metabolic substrates
Effector cells
Granulocytes	Phagocytosis, cytokine production, protein and enzyme secretion, destruction of pathogens
Monocytes/macrophages	Phagocytosis, cytokine production, protein and enzyme secretion, destruction of pathogens
Dendritic cells	Phagocytosis, cytokine production, protein and enzyme secretion, destruction of pathogens
Natural killer (NK) cells	Lysis of infected and tumoral cells, activation of macrophages through cytokine production
Innate lymphoid cells	Mediate immune response and regulate tissue homeostasis and inflammation
Endothelial/epithelial cells	Microbial recognition, cytokine production
Antimicrobial peptides
	Destruction of invading pathogens
Soluble mediators
Cytokines
TNF-α, IL-1, chemokines	Mediate immune response and inflammation
IFN-α	Involved in resistance to viral infection
IFN-γ	Involved in resistance to intracellular pathogen infection and activation of macrophages
IL-12	Stimulates IFN-γ production by NK cells and T lymphocytes
IL-15	Stimulates NK cell proliferation
IL-10	Regulates and controls the inflammation process
TGF-β	Regulates and controls the inflammation process
Seric proteins
Complement system	Opsonization, destruction of pathogens, and T lymphocyte activation
Collectins	Opsonization of pathogens and complement activation
C reactive protein	Opsonization of pathogens and complement activation
Coagulation system	Localization of damage or infected tissue
Cellular receptors
TLRs	Recognize a variety of microbial components
NLRs	Sense bacterial components present in the cytoplasm
CLRs	Recognize sugar moieties of bacteria and fungi
RLRs	Sense viral RNA

TNF: Tumor necrosis factor; IFN: interferon; IL: interleukin; TGF: transforming growth factor; TLR: Toll-like receptor; NLR: Nod-like receptor; CLR: C-type lectin receptor; RLR: RIG-I-like receptor.

Pathogen Recognition

An infection may be intracellular or extracellular, depending on the pathogen. All viruses infect cells and replicate within those cells (intracellularly), whereas bacteria and other parasites may replicate intracellularly or extracellularly, depending on the species. The innate immune system must respond accordingly: by identifying the extracellular pathogen and/or by identifying host cells that have already been infected. When a pathogen enters the body, cells in the blood and lymph detect the specific pathogen-associated molecular patterns (PAMPs) on the pathogen’s surface. PAMPs are carbohydrate, polypeptide, and nucleic acid “signatures” that are expressed by viruses, bacteria, and parasites but which differ from molecules on host cells. The immune system has specific cells, described in Figure 1 and , with receptors that recognize these PAMPs. A macrophage is a large phagocytic cell that engulfs foreign particles and pathogens. Macrophages recognize PAMPs via complementary pattern recognition receptors (PRRs). PRRs are molecules on macrophages and dendritic cells which are in contact with the external environment. A monocyte is a type of white blood cell that circulates in the blood and lymph and differentiates into macrophages after it moves into infected tissue. Dendritic cells bind molecular signatures of pathogens and promote pathogen engulfment and destruction. Toll-like receptors (TLRs) are a type of PRR that recognizes molecules that are shared by pathogens but distinguishable from host molecules). TLRs are present in invertebrates as well as vertebrates, and appear to be one of the most ancient components of the immune system. TLRs have also been identified in the mammalian nervous system.

Cell type Characteristics Location Image Mast cell Connective tissues, mucous membranes Dilates blood vessels and induces inflammation through release of histamines and heparin. Recruits macrophages and neutrophils. Involved in wound healing and defense against pathogens but can also be responsible for allergic reactions. Macrophage Phagocytic cell that consumes foreign pathogens and cancer cells. Stimulates response of other immune cells. Migrates from blood vessels into tissues. Kills tumor cells and virus-infected cells. Natural killer cell Circulates in blood and migrates into tissues. Dendritic cell Presents antigens on its surface, thereby triggering adaptive immunity. Present in epithelial tissue. including skin, lung and tissues of the digestive tract. Migrates to lymph nodes upon activation. Monocyte Differentiates into macrophages and dendritic cells in response to inflammation Stored in spleen, moves through blood vessels to infected tissues. Neutrophil Migrates from blood vessels into tissues. First responders at the site of infection or trauma, this abundant phagocytic cell represents 50-60 percent of all leukocytes. Releases toxins that kill or inhibit bacteria and fungi and recruits other immune cells to the site of infection. Basophil Responsible for defense against parasites. Releases histamines that cause inflammation and may be responsible for allergic reactions. Circulates in blood and migrates to tissues. Eosinophil Releases toxins that kill bacteria and parasites but also causes tissue damage. Circulates in blood and migrates to tissues.

Figure 1. The characteristics and location of cells involved in the innate immune system are described.