15.4Q: Innate Immunity - Biology

15.4Q: Innate Immunity - Biology

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

The ability of a multicellular organism to defend itself against invasion by pathogens (bacteria, fungi, viruses, etc.) depends on its ability to mount immune responses. This table gives some of the distinguishing features of each type of immunity.

Innate ImmunityAdaptive Immunity
Pathogen recognized by receptors encoded in the germlinePathogen recognized by receptors generated randomly
Receptors have broad specificity, i.e., recognize many related molecular structures called PAMPs (pathogen-associated molecular patterns)Receptors have very narrow specificity; i.e., recognize a particular epitope
PAMPs are essential polysaccharides and polynucleotides that differ little from one pathogen to another but are not found in the host.Most epitopes are derived from polypeptides (proteins) and reflect the individuality of the pathogen.
Receptors are PRRs (pattern recognition receptors)In jawed vertebrates, the receptors are B-cell (BCR) and T-cell (TCR) receptors for antigen
Immediate responseSlow (3–5 days) response (because of the need for clones of responding cells to develop)
Little or no memory of prior exposureMemory of prior exposure
Occurs in all metazoansOccurs in vertebrates only

The Cells of the Innate Immune System

A variety of different types of cells participate in innate immunity. What they all have in common is that the receptors by which they recognize pathogens are limited in their specificity. This is in contrast to the B cells and T cells of the adaptive immune system that generate receptors — BCRs and TCRs respectively — that are exquisitely specific for the pathogen. The players:

  • The several granulocytes of the blood and tissues
    • neutrophils
    • eosinophils
    • basophils and mast cells
  • monocytes and macrophages
  • dendritic cells
  • Innate Lymphoid Cells (ILCs). These are cells that look like lymphocytes but do not have the antigen receptors found on B lymphocytes (BCRs) and T lymphocytes (TCRs). They include cytotoxic Natural Killer (NK) cells and several subsets of non-cytotoxic cells (ILC1, ILC2, ILC3, etc.) each with it own pattern of cytokine secretion and favored targets.

Pathogen-Associated Molecular Patterns (PAMPs)

Pathogens, especially bacteria, have molecular structures that are not shared with their host and are shared by many related pathogens. They are relatively invariant; that is, do not evolve rapidly (in contrast, for example, to such pathogen molecules as the hemagglutinin and neuraminidase of influenza viruses).


  • the flagellin of bacterial flagella
  • the peptidoglycan of Gram-positive bacteria
  • the lipopolysaccharide (LPS, also called endotoxin) of Gram-negative bacteria
  • double-stranded RNA. (Some viruses of both plants and animals have a genome of dsRNA. And many other viruses of both plants and animals have an RNA genome that in the host cell is briefly converted into dsRNA).
  • unmethylated DNA (eukaryotes have many times more cytosines, in the dinucleotide CpG, with methyl groups attached).

Pattern Recognition Receptors (PRRs)

There are three groups:

  1. secreted molecules that circulate in blood and lymph;
  2. surface receptors on phagocytic cells like macrophages that bind the pathogen for engulfment;
  3. cell-surface receptors that bind the pathogen initiating a signal leading to the release of effector molecules (cytokines).

Secreted PRRs

Example: Circulating proteins (e.g., C-reactive protein) that bind to PAMPs on the surface of many pathogens. This interaction triggers the complement cascade leading to the opsonization of the pathogen and its speedy phagocytosis.

Phagocytosis Receptors

Macrophages have cell-surface receptors that recognize certain PAMPs, e.g., those containing mannose. When a pathogen covered with polysaccharide with mannose at its tips binds to these, it is engulfed into a phagosome.

Toll-Like Receptors (TLRs)

Macrophages, dendritic cells, and epithelial cells have a set of transmembrane receptors that recognize different types of PAMPs. These are called Toll-like receptors (TLRs) because of their homology to receptors first discovered and named in Drosophila. Mammals have 12 different TLRs each of which specializes — often with the aid of accessory molecules — in a subset of PAMPs. In this way, the TLRs identify the nature of the pathogen and turn on an effector response appropriate for dealing with it. These signaling cascades lead to the expression of various cytokine genes. Examples:

  • TLR-1: Forms a heterodimer with TLR-2 at the cell surface which binds to the peptidoglycan of Gram-positive bacteria like Streptococci and Staphylococci.
  • TLR-2: With TLR-1, binds cell-wall components of Gram-positive bacteria.
  • TLR-3: Binds to the double-stranded RNA of viruses engulfed in endosomes.
  • TLR-4: Activated by the lipopolysaccharide (endotoxin) in the outer membrane of Gram-negative bacteria like Salmonella and E. coli O157:H7
  • TLR-5: Binds to the flagellin of motile bacteria like Listeria.
  • TLR-6: Forms a heterodimer with TLR-2 and responds to peptidoglycan and certain lipoproteins.
  • TLR-7 and TLR-8: Form a heterodimer that binds to the single-stranded RNA (ssRNA) genomes of such viruses as influenza, measles, and mumps that have been engulfed in endosomes.
  • TLR-9: Binds to the unmethylated CpG of the DNA of bacteria that have been engulfed in endosomes. (The cytosines in the host's CpG dinucleotides often have methyl groups attached.)
  • TLR-11:In mice, it binds proteins expressed by several infectious protozoans (Apicomplexa) as well as, like TLR-5, to flagellin. Humans do not have TLR-11.

In all these cases, binding of the pathogen to the TLR initiates a signaling pathway leading to the activation of NF-κB. This transcription factor turns on many cytokine genes such as those for tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and chemokines, which attract white blood cells to the site. All of these effector molecules lead to inflammation at the site. And even before these late events occur, the binding of Gram-positive bacteria to TLR-2 and Gram-negative bacteria to TLR-4 enhances phagocytosis and the fusion of the phagosomes with lysosomes.

Innate Immunity can trigger Adaptive Immunity

This can occur in several ways:

Macrophages and dendritic cells are phagocytes and are also responsible for "presenting" antigens to T cells to initiate both cell-mediated and antibody-mediated adaptive immune responses.

  • Digested fragments of the engulfed pathogen are returned to the cell surface nestled in the cavity of class II histocompatibility molecules.
  • Gene transcription turned on by the interaction of PAMPs and TLRs causes transmembrane molecules called B7 to appear at the cell surface.
  • T cells have a receptor for B7 called CD28.
  • Simultaneous binding of
    • CD28 to B7 and
    • the antigen/class II complex to TCRs specific for it
  • activates the T cell.
  • This leads to repeated mitotic divisions producing clones of CD4+ T cells that can carry out cell-mediated immune responses and/or stimulate B cells to secrete antibodies of the appropriate specificity

Dendritic cells also engulf self-antigens, e.g., body cells that have died by apoptosis, but because these have no PAMPs associated with them, there is no second signal to activate the T cells.

The interaction of PAMPs and TLRs on dendritic cells causes them to secrete cytokines, including

  • interleukin 12 (IL-12) which stimulates the production of Th1 cells
  • interleukin 23 (IL-23) which stimulates the production of Th17 cells
  • interleukin 6 (IL-6), which interferes with the ability of regulatory T cells to suppress the responses of effector T cells to antigen. A double-negative is a positive.

B cells are also antigen-presenting cells. They bind antigen with their BCRs and engulf it into lysosomes. They then transport the digested fragments to the cell surface incorporated in class II histocompatibility molecules just as macrophages and dendritic cells do. B cells also have TLRs. When a PAMP such as LPS binds the TLR, it enhances the response of the B cell to the antigen.

It has been known for many years that for vaccines to be effective, the preparation must contain not only the antigen but also materials called adjuvants. Several adjuvants contain PAMPs, and their stimulus to the innate immune system enhances the response of the adaptive immune system to the antigen in the vaccine. Pathogens coated with fragments of the complement protein C3 are not only opsonized for phagocytosis but also bind more strongly to B cells that have bound the pathogen through their BCR. This synergistic effect enables antibody production to occur at doses of antigen far lower than would otherwise be needed. Some workers feel that, in fact, adaptive immunity is not possible without the assistance of the mechanisms of innate immunity.

Antimicrobial Peptides

In addition to their innate pathogen-recognition systems, vertebrates (including ourselves), invertebrates (e.g., Drosophila), even plants and fungi secrete antimicrobial peptides that protect them from invasion by bacteria and other pathogens. In fact, probably all multicellular organisms benefit from this form of innate immunity. For humans, the best-studied antimicrobial peptides are the defensins, hepcidin and the cathelicidins


All our epithelial surfaces

  • skin
  • lining of the GI tract
  • lining of the genitourinary tracts
  • lining of the nasal passages and lungs

are protected by defensins.

  • Some defensins are secreted by the epithelial cells themselves; others by Th17 cells and neutrophils.
  • Some are secreted all the time; others only in response to attack by pathogens. (In some cases their genes are turned on by activated TLRs.)
  • They are synthesized from larger gene-encoded precursors which are
  • cut to produce the active peptide.
  • These range in length from 25 to 45 amino acids.
  • In humans, they contain 6 invariant cysteines that form 3 disulfide bonds that assist in producing a secondary structure that consists of 3 strands of anti-parallel beta sheet.
  • They attack the outer surface of the cell membrane surrounding the pathogen eventually punching lethal holes in it. (Unlike eukaryotes, the phospholipids in the outer membrane of bacteria carry a surplus of negative charges, and the positive charges on the defensins probably enable them to penetrate the bacterial membranes while sparing host membranes.)

Curiously, some defensins (β-defensin) also affect coat color (in dogs and mice) and in other ways mimic the effects of melanocyte-stimulating hormone (MSH).


Hepcidin is a peptide of 25 amino acids with a secondary structure (beta sheet) like that of the defensins. It is secreted by the liver and controls the level of iron in the blood and ECF by regulating its release from intracellular stores. Hepcidin secretion is increased in response to invasion by pathogens (fungi and bacteria). Many of these require iron for their virulence and by blocking the release of iron into the blood, hepcidin starves them of this essential factor.


The best known human cathelicidin is LL37, a peptide of 37 amino acids synthesized by macrophages, neutrophils, adipocytes, and epithelial cells (providing antimicrobial protection to our skin and the lining of our urinary tract). Unlike the defensins, its secondary structure is alpha helix.

Like defensins, the gene for LL37 can be turned on by activated TLRs. In macrophages, for example, cathelicidin synthesis within the cell promotes killing of engulfed bacteria like M. tuberculosis, the agent of TB. Activation of the cathelicidin gene requires the presence of the active form of vitamin D (1,25 [OH]2 vitamin D3). This may explain:

  • why people with a deficiency of vitamin D are more susceptible to tuberculosis;
  • the physiological basis for the practice of exposing patients to sunlight in TB sanitariums (before the days of antibiotics).

Antimicrobial Peptides and the GI Tract

The contents of the GI tract (especially the colon) are loaded with bacteria. But most of these cause no trouble thanks to a variety of defenses. Among these is the barrier of antimicrobial peptides that exists from mouth to anus.

  • The epithelium of the mouth and tongue is protected by a layer of antimicrobial peptides as well as those secreted in the saliva.
  • The stomach is also protected by antimicrobial peptides (cut by pepsin from a larger precursor) as well as by the low pH of gastric juice.
  • The liquefied contents that leave the stomach are quickly neutralized by the bicarbonate ions in the pancreatic fluid. However, any bacteria that survived the trip through the stomach (e.g., E. coli has a proton pump that enables it to survive the strong acid of the gastric juice) are kept in check by the antimicrobial peptides secreted by the Paneth cells of the small intestine. So, the contents of the small intestine normally contain only a small population of microbes.
  • Not so for the large intestine (colon). The colon supports an enormous population (>1013) of microorganisms, but these seldom invade its lining thanks to
    • a protective barrier of antimicrobial peptides as well as
    • the protective actions of continuous stimulation of
      • TLR-2s by Gram-positive commensals and
      • TLR-4s by Gram-negative commensals
  • The rectum is also protected by an epithelial barrier of antimicrobial peptides.

Innate immune system

The innate immune system is one of the two main immunity strategies found in vertebrates (the other being the adaptive immune system). The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms. [1]

The major functions of the vertebrate innate immune system include:

  • Recruiting immune cells to sites of infection through the production of chemical factors, including specialized chemical mediators called cytokines
  • Activation of the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells
  • Identification and removal of foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells
  • Activation of the adaptive immune system through a process known as antigen presentation
  • Acting as a physical and chemical barrier to infectious agents via physical measures like skin or tree bark and chemical measures like clotting factors in blood or sap from a tree, which are released following a contusion or other injury that breaks through the first-line physical barrier (not to be confused with a second-line physical or chemical barrier, such as the blood-brain barrier, which protects the extremely vital and highly sensitive nervous system from pathogens that have already gained access to the host's body).

The amazing innate immune response to influenza A virus infection

Influenza A viruses (IAVs) remain a major health threat and a prime example of the significance of innate immunity. Our understanding of innate immunity to IAV has grown dramatically, yielding new concepts that change the way we view innate immunity as a whole. Examples include the role of p53, autophagy, microRNA, innate lymphocytes, endothelial cells and gut commensal bacteria in pulmonary innate immunity. Although the innate response is largely beneficial, it also contributes to major complications of IAV, including lung injury, bacterial super-infection and exacerbation of reactive airways disease. Research is beginning to dissect out which components of the innate response are helpful or harmful. IAV uses its limited genetic complement to maximum effect. Several viral proteins are dedicated to combating innate responses, while other viral structural or replication proteins multitask as host immune modulators. Many host innate immune proteins also multitask, having roles in cell cycle, signaling or normal lung biology. We summarize the plethora of new findings and attempt to integrate them into the larger picture of how humans have adapted to the threat posed by this remarkable virus. We explore how our expanded knowledge suggests ways to modulate helpful and harmful inflammatory responses, and develop novel treatments.

Keywords: Collectin LL-37 interferon neutrophil p53.

Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses

Immunosenescence contributes to a decreased capacity of the immune system to respond effectively to infections or vaccines in the elderly. The full extent of the biological changes that lead to immunosenescence are unknown, but numerous cell types involved in innate and adaptive immunity exhibit altered phenotypes and function as a result of aging. These manifestations of immunosenescence at the cellular level are mediated by dysregulation at the genetic level, and changes throughout the immune system are, in turn, propagated by numerous cellular interactions. Environmental factors, such as nutrition, also exert significant influence on the immune system during aging. While the mechanisms that govern the onset of immunosenescence are complex, systems biology approaches allow for the identification of individual contributions from each component within the system as a whole. Although there is still much to learn regarding immunosenescence, systems-level studies of vaccine responses have been highly informative and will guide the development of new vaccine candidates, novel adjuvant formulations, and immunotherapeutic drugs to improve vaccine responses among the aging population.

Keywords: Adjuvants Aging Immunity Immunosenescence Senolytics Systems biology Vaccinology.

Copyright © 2019. Published by Elsevier Inc.

Conflict of interest statement

Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co. Inc., Avianax, Adjuvance, Valneva, Medicago, Sanofi Pasteur, GlaxoSmithKline, and Emergent Biosolutions. Drs. Poland and Ovsyannikova hold patents related to vaccinia and measles peptide vaccines. Dr. Kennedy holds a patent related to vaccinia peptide vaccines. Dr. Kennedy has received research funding from Merck Research Laboratories to study waning immune responses to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. All other authors declare no competing interests.


Figure 1.. Immune cell populations and the…

Figure 1.. Immune cell populations and the effects of immunosenescence on cellular function.

IRF1 Promotes the Innate Immune Response to Viral Infection by Enhancing the Activation of IRF3

Innate immunity is an essential way for host cells to resist viral infection through the production of interferons (IFNs) and proinflammatory cytokines. Interferon regulatory factor 3 (IRF3) plays a critical role in the innate immune response to viral infection. However, the role of IRF1 in innate immunity remains largely unknown. In this study, we found that IRF1 is upregulated through the IFN/JAK/STAT signaling pathway upon viral infection. The silencing of IRF1 attenuates the innate immune response to viral infection. IRF1 interacts with IRF3 and augments the activation of IRF3 by blocking the interaction between IRF3 and protein phosphatase 2A (PP2A). The DNA binding domain (DBD) of IRF1 is the key functional domain for its interaction with IRF3. Overall, our study reveals a novel mechanism by which IRF1 promotes the innate immune response to viral infection by enhancing the activation of IRF3, thereby inhibiting viral infection.IMPORTANCE The activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. IRF3 plays a critical role in the innate immune response to RNA viral infection. However, whether IRF1 plays a role in innate immunity is unclear. In this study, we demonstrated that IRF1 promotes the innate immune response to viral infection. IRF1 is induced by viral infection. Notably, IRF1 targets and augments the phosphorylation of IRF3 by blocking the interaction between IRF3 and PP2A, leading to the upregulation of innate immunity. Collectively, the results of our study provide new insight into the regulatory mechanism of IFN signaling and uncover the role of IRF1 in the positive regulation of the innate immune response to viral infection.

Keywords: IRF1 IRF3 PP2A innate immunity interferon virus.

Copyright © 2020 American Society for Microbiology.


IRF1 can be induced by viral infection in a JAK/STAT signaling-dependent way. (A…

Ectopic expression of IRF1 promotes…

Ectopic expression of IRF1 promotes the innate immune response to viral infection and…

Silencing of IRF1 inhibits antiviral…

Silencing of IRF1 inhibits antiviral immunity. (A and B) Huh7 cells were transfected…

IRF1 enhances the expression of…

IRF1 enhances the expression of ISGs induced by poly(I·C) and viral infection but…

IRF1 promotes the activation of…

IRF1 promotes the activation of IRF3 by viral infection. (A and B) Luciferase…

IRF1 interacts with IRF3. (A)…

IRF1 interacts with IRF3. (A) The subcellular localization of endogenous IRF1 and IRF3…

IRF1 promotes the innate immune…

IRF1 promotes the innate immune response to viral infection by blocking the IRF3-PP2A…

Schematic model of IRF1-mediated promotion…

Schematic model of IRF1-mediated promotion of the innate immune response to viral infection.…

Ira Mellman

Ira Mellman is Vice President of Research Oncology at Genentech. Ira is a cell biologist with a long standing interest in membrane traffic. His lab is reponsible for key observations leading to the initial discovery of endosomes, the mechanisms of epithelial cell polarity, and the cellular basis of dendritic cell function. Until 2007, Ira was… Continue Reading


An array of approximately 20 types of proteins, called a complement system , is also activated by infection or the activity of the cells of the adaptive immune system and functions to destroy extracellular pathogens. Liver cells and macrophages synthesize inactive forms of complement proteins continuously these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the innate and adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already tagged by the adaptive immune system. This “tagging” involves the attachment of specific proteins called antibodies (discussed in detail later) to the pathogen. When they attach, the antibodies change shape providing a binding site for one of the complement proteins. After the first few complement proteins bind, a cascade of binding in a specific sequence of proteins follows in which the pathogen rapidly becomes coated in complement proteins.

Complement proteins perform several functions, one of which is to serve as a marker to indicate the presence of a pathogen to phagocytic cells and enhance engulfment. Certain complement proteins can combine to open pores in microbial cell membranes and cause lysis of the cells.

33.1 Innate Immune Response

In this section, you will explore the following questions:

  • What are examples of physical and chemical immune barriers?
  • What are the immediate and induced immune responses?
  • What are natural killer cells, and what is their role in immunity?
  • What are the features of histocompatibility class I molecules?
  • How do the proteins in a complement system function to destroy extracellular pathogens?

Connection for AP ® Courses

Much of the information about the different organ systems of vertebrate animals is not within the scope for AP ® . The immune system, however, was chosen for in-depth exploration because all organisms, including humans, must maintain dynamic homeostasis to survive within changing environments. Even the simplest multicellular eukaryotes like sponges and cnidarians have developed cells that specialize in immune defenses to protect against disruptions to homeostasis. News headlines warn us of outbreaks of diseases, including Ebola, measles, flu, and insect-borne viruses such as West Nile and chikungunya, that spread rapidly through populations, often with devastating consequences. We also hear about the emergence of new infections, especially ones caused by bacteria that have evolved resistance to antibiotics.

Immune systems in animals range from a loose cluster of phagocytic cells in sponges to complex interactions of molecules, cells, tissues, and organs that provide immunity in mammals. Components of the immune system constantly search the body for signs of disease-causing microorganisms called pathogens. Immune factors mobilize, identify the nature of the pathogen, strengthen the corresponding cells and molecules to combat the infection, and then halt the immune response after the infection is cleared to avoid unnecessary host cell damage. Because of its programmable memory system, the immune system can remember pathogens and initiate a more rapid response upon re-exposure. The immune response can be either innate or adaptive. The adaptive immune response stores information about past infections and mounts pathogen-specific defense. The innate immune response is always present and defends against all pathogens.

Despite the barriers of skin, tears, and mucus, pathogens may still enter the body. The innate immune system responds with inflammation, pathogen engulfment, and secretion of immune factors and proteins. Several types of cells are involved in the innate immune system, including mast cells that release histamines (causing those annoying symptoms associated with allergies and colds), macrophages that consume pathogens and cancer cells, natural killer (NK) cells that destroy tumor cells and virus-infected cells, several types of white blood cells, and even protective proteins like complement and interferon. We know from experience, however, that these barriers can fail. Fortunately, adaptive immune responses provide another, more specific line of defense.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 2 of the AP ® Biology Curriculum Framework. The AP ® Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP ® Biology course, an inquiry-based laboratory experience, instructional activities, and AP ® exam questions. A learning objective merges required content with one or more of the seven science practices.

Big Idea 2 Biological systems utilize free energy and molecular building blocks to grow, to reproduce, and to maintain dynamic homeostasis.
Enduring Understanding 2.D Growth and dynamic homeostasis of a biological system are influenced by changes in the system’s environment.
Essential Knowledge 2.D.4 Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis.
Science Practice 1.1 The student can create representations and models of natural or man-made phenomena and systems in the domain.
Science Practice 1.2 The student can describe representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective 2.30 The student can create representations or models to describe nonspecific immune defenses in animals.

The immune system comprises both innate and adaptive immune responses. Innate immunity occurs naturally because of genetic factors or physiology it is not induced by infection or vaccination but works to reduce the workload for the adaptive immune response. Both the innate and adaptive levels of the immune response involve secreted proteins, receptor-mediated signaling, and intricate cell-to-cell communication. The innate immune system developed early in animal evolution, roughly a billion years ago, as an essential response to infection. Innate immunity has a limited number of specific targets: any pathogenic threat triggers a consistent sequence of events that can identify the type of pathogen and either clear the infection independently or mobilize a highly specialized adaptive immune response. For example, tears and mucus secretions contain microbicidal factors.

Physical and Chemical Barriers

Before any immune factors are triggered, the skin functions as a continuous, impassable barrier to potentially infectious pathogens. Pathogens are killed or inactivated on the skin by desiccation (drying out) and by the skin’s acidity. In addition, beneficial microorganisms that coexist on the skin compete with invading pathogens, preventing infection. Regions of the body that are not protected by skin (such as the eyes and mucus membranes) have alternative methods of defense, such as tears and mucus secretions that trap and rinse away pathogens, and cilia in the nasal passages and respiratory tract that push the mucus with the pathogens out of the body. Throughout the body are other defenses, such as the low pH of the stomach (which inhibits the growth of pathogens), blood proteins that bind and disrupt bacterial cell membranes, and the process of urination (which flushes pathogens from the urinary tract).

Despite these barriers, pathogens may enter the body through skin abrasions or punctures, or by collecting on mucosal surfaces in large numbers that overcome the mucus or cilia. Some pathogens have evolved specific mechanisms that allow them to overcome physical and chemical barriers. When pathogens do enter the body, the innate immune system responds with inflammation, pathogen engulfment, and secretion of immune factors and proteins.

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 33.2 and shown in Figure 33.3, 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.

Effects of Cytokine Release

The binding of PRRs with PAMPs triggers the release of cytokines, which signal that a pathogen is present and needs to be destroyed along with any infected cells. A cytokine is a chemical messenger that regulates cell differentiation (form and function), proliferation (production), and gene expression to affect immune responses. At least 40 types of cytokines exist in humans that differ in terms of the cell type that produces them, the cell type that responds to them, and the changes they produce. One type cytokine, interferon, is illustrated in Figure 33.4.

One subclass of cytokines is the interleukin (IL), so named because they mediate interactions between leukocytes (white blood cells). Interleukins are involved in bridging the innate and adaptive immune responses. In addition to being released from cells after PAMP recognition, cytokines are released by the infected cells which bind to nearby uninfected cells and induce those cells to release cytokines, which results in a cytokine burst.

A second class of early-acting cytokines is interferons, which are released by infected cells as a warning to nearby uninfected cells. One of the functions of an interferon is to inhibit viral replication. They also have other important functions, such as tumor surveillance. Interferons work by signaling neighboring uninfected cells to destroy RNA and reduce protein synthesis, signaling neighboring infected cells to undergo apoptosis (programmed cell death), and activating immune cells.

In response to interferons, uninfected cells alter their gene expression, which increases the cells’ resistance to infection. One effect of interferon-induced gene expression is a sharply reduced cellular protein synthesis. Virally infected cells produce more viruses by synthesizing large quantities of viral proteins. Thus, by reducing protein synthesis, a cell becomes resistant to viral infection.

Phagocytosis and Inflammation

The first cytokines to be produced are pro-inflammatory that is, they encourage inflammation, the localized redness, swelling, heat, and pain that result from the movement of leukocytes and fluid through increasingly permeable capillaries to a site of infection. The population of leukocytes that arrives at an infection site depends on the nature of the infecting pathogen. Both macrophages and dendritic cells engulf pathogens and cellular debris through phagocytosis. A neutrophil is also a phagocytic leukocyte that engulfs and digests pathogens. Neutrophils, shown in Figure 33.3, are the most abundant leukocytes of the immune system. Neutrophils have a nucleus with two to five lobes, and they contain organelles, called lysosomes, that digest engulfed pathogens. An eosinophil is a leukocyte that works with other eosinophils to surround a parasite it is involved in the allergic response and in protection against helminthes (parasitic worms).

Neutrophils and eosinophils are particularly important leukocytes that engulf large pathogens, such as bacteria and fungi. A mast cell is a leukocyte that produces inflammatory molecules, such as histamine, in response to large pathogens. A basophil is a leukocyte that, like a neutrophil, releases chemicals to stimulate the inflammatory response as illustrated in Figure 33.5. Basophils are also involved in allergy and hypersensitivity responses and induce specific types of inflammatory responses. Eosinophils and basophils produce additional inflammatory mediators to recruit more leukocytes. A hypersensitive immune response to harmless antigens, such as in pollen, often involves the release of histamine by basophils and mast cells.

Cytokines also send feedback to cells of the nervous system to bring about the overall symptoms of feeling sick, which include lethargy, muscle pain, and nausea. These effects may have evolved because the symptoms encourage the individual to rest and prevent them from spreading the infection to others. Cytokines also increase the core body temperature, causing a fever, which causes the liver to withhold iron from the blood. Without iron, certain pathogens, such as some bacteria, are unable to replicate this is called nutritional immunity.


Watch this 23-second stop-motion video showing a neutrophil that searches for and engulfs fungus spores during an elapsed time of about 79 minutes.

  1. Neutrophils phagocytize pathogens invading the body and release chemical histamines that cause pathogen destruction and removal from the body. This prevents pathogens from producing toxic compounds that harm cells.
  2. Neutrophils phagocytize pathogens invading the body, resulting in their death and removal from the body. This prevents pathogens from multiplying or producing toxic compounds that harm human cells.
  3. Neutrophils are phagocytic and are the first responders to infection. They produce large quantities of cytokines, which cause pathogen destruction and removal from the body.
  4. Neutrophils produce cytokines that help phagocytes to recognize foreign material that will destroy and remove pathogens from the body.

Natural Killer Cells

Lymphocytes are leukocytes that are histologically identifiable by their large, darkly staining nuclei they are small cells with very little cytoplasm, as shown in Figure 33.6. Infected cells are identified and destroyed by natural killer (NK) cells, lymphocytes that can kill cells infected with viruses or tumor cells (abnormal cells that uncontrollably divide and invade other tissue). T cells and B cells of the adaptive immune system also are classified as lymphocytes. T cells are lymphocytes that mature in the thymus gland, and B cells are lymphocytes that mature in the bone marrow. NK cells identify intracellular infections, especially from viruses, by the altered expression of major histocompatibility class (MHC) I molecules on the surface of infected cells. MHC I molecules are proteins on the surfaces of all nucleated cells, thus they are scarce on red blood cells and platelets which are non-nucleated. The function of MHC I molecules is to display fragments of proteins from the infectious agents within the cell to T-cells healthy cells will be ignored, while “non-self” or foreign proteins will be attacked by the immune system. MHC II molecules are found mainly on cells containing antigens (“non-self proteins”) and on lymphocytes. MHC II molecules interact with helper T-cells to trigger the appropriate immune response, which may include the inflammatory response.

An infected cell (or a tumor cell) is usually incapable of synthesizing and displaying MHC I molecules appropriately. The metabolic resources of cells infected by some viruses produce proteins that interfere with MHC I processing and/or trafficking to the cell surface. The reduced MHC I on host cells varies from virus to virus and results from active inhibitors being produced by the viruses. This process can deplete host MHC I molecules on the cell surface, which NK cells detect as “unhealthy” or “abnormal” while searching for cellular MHC I molecules. Similarly, the dramatically altered gene expression of tumor cells leads to expression of extremely deformed or absent MHC I molecules that also signal “unhealthy” or “abnormal.”

NK cells are always active an interaction with normal, intact MHC I molecules on a healthy cell disables the killing sequence, and the NK cell moves on. After the NK cell detects an infected or tumor cell, its cytoplasm secretes granules comprised of perforin, a destructive protein that creates a pore in the target cell. Granzymes are released along with the perforin in the immunological synapse. A granzyme is a protease that digests cellular proteins and induces the target cell to undergo programmed cell death, or apoptosis. Phagocytic cells then digest the cell debris left behind. NK cells are constantly patrolling the body and are an effective mechanism for controlling potential infections and preventing cancer progression.


An array of approximately 20 types of soluble proteins, called a complement system, functions to destroy extracellular pathogens. Cells of the liver and macrophages synthesize complement proteins continuously these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the antibody response of the adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. Binding of complement proteins occurs in a specific and highly regulated sequence, with each successive protein being activated by cleavage and/or structural changes induced upon binding of the preceding protein(s). After the first few complement proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement proteins.

Complement proteins perform several functions. The proteins serve as a marker to indicate the presence of a pathogen to phagocytic cells, such as macrophages and B cells, and enhance engulfment this process is called opsonization. Certain complement proteins can combine to form attack complexes that open pores in microbial cell membranes. These structures destroy pathogens by causing their contents to leak, as illustrated in Figure 33.7.

15.4Q: Innate Immunity - Biology

Organs Involved in Innate Immunity

  • Eyes: tears wash away pathogens and have bacteriocidal enzymes.
  • Skin: Difficult for a pathogen to penetrate, sweat creates high salt conditions, oil layer makes an inhospitable environment.
  • Stomach: acid kills pathogens and sterilizes food.
  • Nose: Mucus traps pathogens which are swallowed or blown out.
  • Mouth: Natural microbiota prevents growth of opportunistic pathogens.
  • Lungs: mucus lining of lungs traps pathogens and cilia move particles out to throat and it is swallowed.
  • Large intestine: Natural microbiota prevents growth of opportunistic pathogens.
  • Reproductive system: acid conditions and natural microbiota.

Innate Immunity Influences

  • Age
  • Nutrition
  • Endocrine functions: disorders including diabetes, hyperthyroidism, adrenal dysfunction and stress.

Mechanisms of Innate Immunity

  • Non-specific broad spectrum response.
  • No lasting immunological memory.
  • Has limited flexibility and repertoire.
  • Responses are evolutionarily ancient.

This module presents the concepts of Innate Immunity which is a nonspecific inherited immune system to prevent infection. This type of immunity acts on the species, race and individual levels. A given species may have an immunity to a pathogen however individuals or races within the species may have modified specific responses.

The primary mechanisms involved in innate immunity are presented. These mechanisms include: anatomic, physiologic, phagocytic and inflammatory barriers and responses. The organism uses a combination of responses and innate immunity retains no lasting immune memory.

  • Basic concepts of innate immunity.
  • Species, race and individual parameters of innate immunity.
  • Body systems involved in innate immunity.
  • Factors that influence innate immunity.
  • Mechanisms of innate immunity.
  • Innate Immune responses: Anatomic, Physiologic, Phagocytic and Inflammatory.
  • Images and diagrams showing the relationship between innate immunity and adaptive immunity.
  • Concept map showing inter-connections of concepts.
  • Definition slides introduce terms as they are needed.
  • Examples given throughout to illustrate how the concepts apply.
  • A concise summary is given at the conclusion of the tutorial.

Immune system consists of two processes: Innate Immunity and Adaptive Immunity.
Determinants affecting innate immunity, genetics and environmental factors.
There are specific organs and systems involved in innate immunity that are shared within defined groups such as species, races etc.
Organs and systems involved in innate immunity: eyes, skin, stomach, large intestine, nose, mouth, lungs and reproductive system.
The systems interact to complement each others innate immune functions, e.g. mucous in the nose traps pathogens and particles which are transported to the stomach where they are sterilized.
Innate immunity may be considered at the level of the species, race or individual.

Factors affecting innate immunity include: age, hormonal levels, nutrition and stress.

See all 24 lessons in college biology, including concept tutorials, problem drills and cheat sheets:
Teach Yourself Microbiology Visually in 24 Hours

© 2014 Rapid Learning Center. Privacy | Disclaimer Home | Order | Preview | Review | About | Contact
Chemistry Survival, Biology Survival, Physics Survival and
Mathematics Survival Publishing are the divisions of Rapid Learning Inc.


In February 2012, a new version of InnateDB was released that included the incorporation of bovine gene, pathway and molecular interaction annotation in addition to the existing data for human and mouse. This new version of the platform now also facilitates a systems biology approach to the investigation of the bovine innate immune response and is poised to deepen our understanding of important bovine infectious diseases associated with significant economic losses (e.g. bovine tuberculosis and mastitis), as well as enabling cross-species comparisons of innate immunity.

As bovine experimentally validated interactions and pathways are virtually non-existent, InnateDB uses an orthology-based approach to predict bovine pathways and interactions primarily from human data. One should be aware that this approach results in a humanized and frequently incomplete representation of the bovine interactome, but in the absence of widespread experimental data it provides at least a network biology framework to build on and to generate hypotheses that can be subsequently experimentally validated. InnateDB experimentally validated and predicted interactions are clearly labelled. As of September 2012, InnateDB contains >70 000 bovine interologs (interactions based on orthology) involving 10 717 bovine genes. In each case, one can link back to the orthologous human interaction to review evidence for the interaction.

The latest release of InnateDB also uses orthology predictions to transfer human and mouse pathway annotations to bovine genes in real time. Currently, pathway annotations can be assigned to 7032 bovine genes by orthology to human genes. Notably, although only ∼70% of all human genes (14 316 genes) have a predicted bovine ortholog, and a significantly higher proportion (85%) of human genes with pathway annotations have a bovine ortholog. This higher prevalence of conserved genes among pathway-annotated genes indicates that many of the associated processes may be well preserved.

To further examine the appropriateness of the orthology-based annotation transfer on a per-pathway basis, we determined the ‘conservation rate’ (cons) of each pathway, defined as the ratio of pathway participants in the source organism (human/mouse) that have a putative counterpart in the target organism (cow) to the total number of participants in the source organism. As of September 2012, InnateDB contains 1536 human pathways with five or more pathway participants, 80% (1257 pathways) of these have a conservation rate of 0.8 or better. The corresponding number for a conservation rate of ≥0.7 is 93% (1442 pathways). The high prevalence of strongly conserved pathways seems to largely justify an orthology-based approach for inferring bovine pathways. Supplementary Table S1 lists the remaining 107 pathways with a relatively low conservation rate (cons <0.7). Notably, the list of pathways for which an orthology-based reconstruction is challenging includes >30 immunologically important pathways. In some cases, the low conservation rate can be attributed to real divergence of the underlying processes. The bovine Type I Interferon family, for example, has been shown to have undergone widespread expansion, including the divergence of a new Type I interferon (IFN) family (IFNX) in the cow from IFN alpha ( 15). In other cases, the conservation rate might further increase with future improvements to the quality of the bovine draft genome.

In addition to orthology-based annotation transfer, the tissue expression profile of a gene can provide some insight into its potential function ( 16). Through collaboration with colleagues at the United States Department of Agriculture, InnateDB now integrates bovine tissue expression data for >13 000 genes. This data was sourced from the Bovine Gene Atlas ( 17), which has profiled gene expression across 87 different bovine tissues using a next generation sequencing approach. A graphical tissue expression profile is available on the Gene Card page of bovine genes.