Chapter 17 Review Sheets - Innate Nonspecific Host Defenses

What are the two general types of immunity?

1. Nonspecific Innate Immunity

2. Specific Adaptive Immunity

Explain what Nonspecific Innate Immunity is.

Responds to a broad range of pathogens in the same way

What are the three types of Nonspecific Innate Immunity?

1. Physical

2. Chemical

3. Cellular

Endothelial cells that line blood vessels have very tight cell-to-cell junctions.

Explain why this would be important and generally explain the importance of cell-to-cell junctions in immunity.

Tight junctions rivet two adjacent cells together, preventing or limiting material exchange through the spaces between them.

Cell-to-cell junctions prevent invaders from crossing through to deeper tissue.

What are some bacterial defenses (think back to Chapter 16) that can be used to overcome that type of physical defense (like Cell-to-cell junctions)?

Invading microorganisms might attempt to break down substances chemically, using enzymes like Proteases that can cause structural damage to create a point of entry for pathogens.

What are the three layers of the skin and what is found in each layer?

1. Epidermis —> cells packs with Keratin, dead skin cells

2. Dermis —> hair follicles, sweat glands, nerves, and blood vessels

3. Hypodermis —> blood and lymph vessels

What is the role of Keratin and Fatty Acids in the Epidermis?

Keratin —> makes the skin’s surface mechanically tough and resistant to degradation by bacterial enzymes

Fatty Acids —> create a dry, salty, and acidic environment that inhibits the growth of some microbes and is highly resistant to breakdown by bacterial enzymes

While the skin provides a physical barrier, there are also mechanical components to its ability to protect the host.

How does shedding of skin protect the host?

When the dead cells of the Epidermis are shed, anu microbes clinging to them are also shed along with them. Shed skin cells are continually replaced with new cells from below, providing a new barrier that will soon be shed in the same way.

Where in the body do you find mucous membranes?

Nose, mouth, lungs, and urinary & digestive tracts

What are the characteristics of mucus that help protect the host?

Texture and Antimicrobial peptides

What is a Ciliated Epithelial Cell?

Hair-like cells in the respiratory tract that beat, pushing mucus secretions and trapped debris away from the sensitive tissues of the lungs

What is the mucociliary escalator?

System in which mucus and debris are propelled up and out of the respiratory tract by the beating of respiratory cilia and the mechanical actions of coughing and / or swallowing

What is a Goblet Cell?

Specialized type of epithelial cell that secrete mucins, which are significant components of mucus

What is Peristalsis?

Muscular contractions of the gastrointestinal that propel ingested material through the stomach, intestines, and eventually through the rectum and out of the body

What is the Endothelia?

Layer of epithelial cells lining blood vessels, lymphatics, the blood-brain barrier, and some other tissues

Why are the tight junctions of cells associated with the blood-brain barrier important?

They prevent any transient microbes in the bloodstream from entering the CNS, keeping the cerebrospinal fluid that surrounds the brain and spinal cord sterile under normal conditions

Is the Central Nervous System sterile?

Yes

Name two mechanical defenses that protect the eye.

1. Tears

2. Eyelashes

How is urine an example of a mechanical defense?

Urine passing out of the body washes out transient microorganisms in the urinary tract, preventing them from taking up residence

What are the ways in which normal microflora help to protect the host?

• Occupy available space

• Compete for available nutrients

Why would fecal transplantation be considered as a potential therapy for diseases caused by C. diff?

The transfer of fecal material from a donor (screened for potential pathogens) into the intestines of the recipient patient can be used as a method for restoring the normal microbiota and combating C. difficile infections

What is the difference between Endogenous and Exogenous chemical mediators?

Endogenous — produced by human body cells

Exogenous — produced by certain microbes that are part of the microbiome

Are chemical mediators always produced?

No; some are continual, others are stimulus-driven

What is Sebum?

What is the role of Sebum in innate immunity?

Sebum — oil released by sebaceous glands in the dermis that is released onto the skin surface through hair follicles; endogenous mediator

Provides an additional layer of defense by helping seal off the pore of the hair follicle, preventing bacteria on the skin’s surface from invading sweat glands and surrounding tissue

Propionibacterium acnes uses a ____________ to break down sebum, resulting in a compound called ____________.

Lipase enzyme

Oleic Acid

Oleic Acid would be an example of an ____________ mediator.

Exogenous

Which chemical mediators are found in the digestive tract?

Saliva (oral cavity) —> Lactoperoxidase (enzyme)

Mucus (esophagus) —> Lysozyme (enzyme)

Highly acidic gastric fluid (stomach)

Intestines (lower digestive tract) —> pancreatic and intestinal enzymes, antibacterial peptides (cryptins), bile from the liver, and specialized Paneth cells that produce Lysozyme

Why is lowering the pH of the system a way to protect the host against pathogens?

How do microorganisms do this?

Lowering the pH / increasing the acidity can inhibit the growth of many microbes and potential pathogens

They do this by fermentation, which produces acidic products

In what parts of the body is a low pH present?

Urinary Tract (urine), Vagina, and Ears (earwax / cerumen)

What does earwax do to protect the host?

Exhibits antimicrobial properties due to the presence of fatty acids, which lower the pH to between 3 and 5

What are the functions of Lactoferrin, Lactoperoxidase, and Lysozyme?

Lactoferrin —> inhibits microbial growth by chemically binding and sequestering iron

Lactoperoxidase —> catalyzes oxidation of substrates into bactericidal products (SCN- and H2O2)

Lysozyme —> cleaves the bond between NAG and NAM in peptidoglycan, a component of the cell wall in bacteria

Where are Lactoferrin, Lactoperoxidase, and Lysozyme found?

Respiratory Tract, tears, saliva

How do chemical defenses function in the respiratory tract?

Mucus (nasal passages) —> contains mix of antimicrobial molecules

Secretions (trachea and lungs) —> contains Lysozyme, Lactoferrin, and additional chemical mediators, like Surfactant

What are some important aspects about Antimicrobial Peptides (AMP)?

• Can be broad and narrow spectrum, depending on the antimicrobial mechanism

• Constitutively and induced expression

• Can:

  • Damage membranes

  • Damage nucleic acids

  • Inhibit cell wall synthesis

• Are found in several places in and on the body

• Are Endogenous and Exogenous

  • Transferred through HORIZONTAL Gene Transfer

What are Antimicrobial Peptides (AMP)?

Special class of nonspecific cell-derived mediators with broad-spectrum antimicrobial properties

Who produces Antimicrobial Peptides?

Where are they found?

Why are they considered to be antimicrobials?

Produced by many sources across all kinds of kingdoms or sumn

Found everywhere…

Can induce cell damage in microorganisms in a variety of ways

Bacteriocins are an example of exogenously produced AMPs.

What are some important characteristics of Bacteriocins?

Secreted By —> Resident microbiota

Body Site —> Gastrointestinal Tract

Pathogens Inhibited —> Bacteria

Mode of Action —> Disrupt Membrane

Defensins are an example of endogenously produced AMPs.

What are some important characteristics of Defensins?

Secreted By —> Epithelial cells, Macrophages, Neutrophils

Body Site —> Throughout the body

Pathogens Inhibited —> Fungi, Bacteria, and many viruses

Mode of Action —> Disrupt membrane

What are the different types of Plasma protein mediators?

1. Acute-Phase Proteins

2. Complement Proteins

3. Cytokines

What are Acute Phase Proteins?

Antimicrobial molecules produced by liver cells in response to pathogen-induced stimulation events

Explain the function of C-Reactive Protein, Ferritin, and Mannose Binding Lectin

C-Reactive Protein —> coats bacteria (opsonization), preparing them for indigestion by Phagocytes

Ferritin —> bind and sequester iron, thereby inhibiting the growth of pathogens

Mannose Binding Lectin —> activates complement cascade

What is complement?

Series of proteins that can become activated in the presence of invading microbes, resulting in opsonization, inflammation, and lysis of pathogens

What is the Alternative Pathway of complement activation?

Spontaneous activation of the complement protein

What is the Classical Pathway of complement activation?

More efficient mechanism; specific antibody must first bind to the pathogen to form an antibody-antigen complex to initiate the pathway

What is the Lectin Activation Pathway of complement activation?

Similar to the Classical Pathway; triggered by the binding of Mannose-Binding Lectin (an acute-phase protein) to carbohydrates on the microbial surface

Which of the Complement activation pathways is part of the innate immune response?

Alternative Pathway

What happens to C3b if pathogens are present?

Absent?

Present —> C3b attaches to the surface of the microbes an recruits other complement proteins in a cascade

Absent —> C3b is quickly degraded in a hydrolysis reaction using the water in blood

What are the three outcomes of complement?

1. Opsonization

2. Inflammation

3. Cytolysis of Pathogens

What is Opsonization?

Pathogen is coated in a chemical substance (an opsonin) that allows phagocytic cells to recognize, engulf, and destroy the pathogen more easily

What is Inflammation?

Innate nonspecific immune response characterized by erythema, edema, heat, pain, and altered function, typically at the site of injury / infection, but sometimes becoming systemic

Where would we find complement proteins?

In the Membrane Attack Complex (MAC), from the liver and circulating in our blood

Which proteins are important for Opsonization?

Inflammation?

Cytolysis?

Opsonization —> C1q, C3b, and C4b

Inflammation —> C3a and C5a

Cytolysis —> C5 to C9

What is the MAC Complex?

Why is it only effective against Gram-Negative bacteria?

Ring structure formed from complement proteins C6 through C9 that penetrates the membranes of a targeted cell, causing cell lysis and death

Cannot penetrate the thick layer of peptidoglycan associated with Gram-Positive bacterial cell walls

Is complement generally only effective against Gram-Negative bacteria?

Yes

Why is complement not always “activated”?

Precursor proteins that make up the complement system become activated when stimulated or triggered by a variety of factors, including the presence of microorganisms

What are Cytokines?

Protein molecules that act as chemical signals; produced by cells in response to a stimulation event — soluble proteins

What cells send and receive Cytokines?

Immune Cells (example, Macrophages)

Explain the difference between Autocrine, Paracrine, and Endocrine signaling.

Autocrine — same cell secretes and receives cytokine signal

Paracrine — cytokine signal secreted to a nearby cell

Endocrine — cytokine signal secreted to circulatory system; travels to distant cells

What are Interleukins?

Cytokines largely produced by immune system cells that help coordinate efforts against invading pathogens

What are Chemokines?

Chemotactic Cytokines that recruit specific subsets of leukocytes to infections, damaged tissues, and sites of inflammation

What are Interferons?

Cytokines released by cells that have been infected by a virus; stimulate antiviral responses in nearby cells as well as the cells secreting the interferons

Why would interferons trigger cells to stop producing and destroy mRNA and proteins?

Why is this message going to nearby cells?

These cellular changes inhibit viral replication and production of mature virus, slowing the spread of the virus.

This message is going to nearby cells so as to help prevent additional neighboring cells from becoming infected, thus stemming the infection.

What type of cell would produce interferons?

Cells infected with a virus

Explain the different outcomes associated with interferon messaging.

1. Neighboring uninfected cells destroy RNA and reduce protein synthesis

2. Neighboring infected cells undergo apoptosis

3. Activates immune cells

Explain the role of Mast Cells in inflammation and fever production.

When binded to Cytokines, Mast Cells release Histamine and Leukotrienes

• Histamine — mediates proinflammatory events (Bronchoconstriction and smooth muscle contraction)

• Leukotrienes — induce coughing, vomiting, and diarrhea, which serve to expel pathogens

What activates Mast Cells?

Cytokines

What is Histamine?

Proinflammatory molecule released by Basophils and Mast Cells in response to stimulation by other Cytokines and chemical mediators

What are Leukotrienes?

Lipid-based chemical mediators produced by Leukocytes and other tissue cells; promote inflammation and allergic responses

What is Bradykinin?

Activated form of a proinflammatory molecule induced in the presence of invader microbes; opens gaps between cells in blood vessels, allowing fluid and cells to leak into surrounding tissue

What are the formed elements of the blood?

1. Red Blood Cells (RBCs; also called Erythrocytes)

2. Platelets (also called Thrombocytes)

3. White Blood Cells (WBCs; also called Leukocytes)

What is the primary role of each of the formed elements of the blood?

Which of these elements plays a role in the innate immune response?

RBCs —> carry oxygen to tissues

Platelets —> cellular fragments that participate in blood clot formation and tissue repair

WBCs —> participate in various nonspecific mechanisms of INNATE and adaptive immunity

White Blood Cells play a role in the Innate Immune Response

What cell type do the formed elements differentiate from?

Which formed element is formed in the greatest amounts?

All the formed elements differentiate from hematopoietic stem cells in the bone marrow

WBCs are formed in the greatest amounts

White Blood Cells (Leukocytes) are divided into what two general categories?

How can one differentiate between the two categories?

1. Granulocytes — numerous granules visible in the cytoplasm

2. Agranulocytes — lack granules

By looking under a microscope, how would one differentiate between an Eosinophil, Neutrophil, and a Basophil?

Neutrophil —> nucleus with 3 - 5 lobes and small, numerous, lilac-colored granules

• Each lobe is connected by a thin strand of material to the other lobes

Eosinophil —> fewer lobes in nucleus (~2 - 3) and larger granules that stain reddish-orange

Basophil —> two-lobed nucleus and large granules that stain dark blue or purple

Figure 17.14

Which category of Leukocyte would Neutrophils, Eosinophils, and Basophils belong to?

Granulocytes

Which compound released by Eosinophils is linked to asthma sufferers?

Eosinophil Peroxidase (EPO)

What is the purpose of Eosinophils?

How do they achieve their goals?

They protect against Protozoa and Helminths

Their granules contain Histamine, degradative enzymes, and a compound called Major Basic Protein (MBP)

• MBP disrupts the cell membrane and permeability of parasites by binding to their surface carbohydrates

What do Basophils do?

What dye do they absorb?

Promote chemotaxis and release Histamine, which opens the gaps between cells in the blood vessels

Absorbs Methylene Blue

What complement proteins activate the Basophil?

C3a and C5a (Anaphylatoxins)

How is the Basophil linked to the acquired immune response?

Activated via antibodies

Which Leukocytes are linked to allergies?

Eosinophils, Basophils, and Mast Cells

Compare and contrast Mast Cells and Basophils.

Similarities:

• Contain many of the same components in their granules and play similar roles in allergic responses and other inflammatory responses

Differences:

• Mast cells leave the circulating blood and are most frequently found residing in tissues

What two groups of cells are Agranulocytes separated into?

1. Lymphocytes

2. Monocytes

What are the three types of Lymphocytes?

1. Natural Killer Cells (NK Cells)

2. B. Cells

3. T. Cells

What are the two types of Monocytes?

1. Macrophages

2. Dendritic Cells

What types of cells do Natural Killer Cells (NK Cells) destroy?

Cells that are abnormal in some way — examples includes Cancer cells and cells infected with viruses

How are NK Cells able to recognize the difference between a “normal” cell and an “abnormal” cell?

Can recognize normal MHC markers on the surface of healthy cells and these markers serve as an inhibitory signal preventing NK cell activation

Cancer cells and other virus-infected cells actively diminish or eliminate expression of MHC markers on their surface, which NK cells interpret as an abnormality and a cell in distress

What are the two different mechanisms an NK cell can use to destroy its target cell?

1. May express cytotoxic membrane proteins and cytokines that stimulate the target cell to undergo apoptosis

2. May use perforin-mediated cytotoxicity to induce apoptosis in target cells

How do Perforin and Granzymes work together?

Perforin creates pores in the target cell and granzymes enter through these protes into the cytoplasm of the target cell, where they trigger a cascade of protein activation that leads to apoptosis

What is a Monocyte?

Large, agranular, mononuclear leukocytes found in the peripheral blood that are responsible for phagocytosis of pathogens and damaged cells

Describe the difference between a Monocyte and a Macrophage.

Macrophages are Monocytes that have migrated from the bloodstream into any tissue of the body

What is an Antigen-Presenting Cell?

Macrophages, Dendritic Cells, and B Cells that process and present foreign pathogen antigens for the purpose of activating T cells and adaptive immune responses

How does a Macrophage destroy its target cell?

They secrete antimicrobial mediators and pro-inflammatory cytokines

What is the difference between a Macrophage and a Dendritic Cell?

Macrophage:

• Remain in tissues

• First responder

• Phagocytosis

• Release Cytokines

Dendritic Cells:

• Differ in structure and general location

• Tend to be found near “ports of injury”

• Primarily take up small soluble antigens

What is a Pathogen-Associated Molecular Pattern?

Common molecular motifs found on pathogens

What are some examples of Pathogen-Associated Molecular Patterns?

• Nucleic Acids (Ex. viral DNA or DNA)

• Peptidoglycan, in bacterial cell wall

• Flagellin (protein found in bacterial flagella)

• Lipopolysaccharide (LPS) from the outer membrane of Gram-Negative Bacteria

• Lipopeptides (molecules expressed by most bacteria)

What is a Pattern-Recognition Receptor?

Where is it located?

Receptors on the surface or in the interior of phagocytic cells that bind to pathogen-associated molecular patterns (PAMPs)

When a PRR binds a PAMP, what happens?

Sends a signal to the nucleus that activates genes involved in phagocytosis, cellular proliferation, production and secretion of antiviral interferons and proinflammatory cytokines, and enhances intracellular killing

Describe the process of Phagocytosis.

Large particles are engulfed by membrane invagination, after which the particles are enclosed in a pocket, which is pinched off from the membrane to form a vacuole

What types of Leukocytes are capable of Phagocytosis?

.Neutrophils and Eosinophils

(Monocytes can too)