Nonspecific Host Defenses Lecture Notes

These flashcards cover the key vocabulary and concepts related to nonspecific host defenses as outlined in the lecture notes.

Why are Nonspecific Defenses described as 'Innate'?

Nonspecific defenses are termed 'innate' because they are present at birth and are fully functional before any exposure to infectious agents, providing the body with immediate defense mechanisms.

What is the body's first line of defense?

The first line of defense includes physical and chemical barriers that occur at body surfaces, primarily the skin and mucous membranes, which aim to block the entry of pathogens.

Name some External Body Surfaces.

External body surfaces that act as barriers against pathogens include the skin and the conjunctiva, which is the mucous membrane covering the front of the eye.

Name some Internal Body Surfaces.

Internal body surfaces include the linings of the digestive tract, vagina, respiratory tract, urinary tract, and the external auditory canal, which are all critical in protecting against infections.

Name 5 Nonspecific Defenses on the Skin.

1. Stratified epidermis - Multiple layers of skin cells that provide physical protection.
   

 2. Keratin (drying agent) - A protein that creates a tough outer layer, enhancing skin's barrier function.

3. Fatty acids (acidic) - Secreted by sebaceous glands, these lower skin pH, inhibiting pathogen growth.
   

4. Salty perspiration (hypertonic) - High salt concentration can dehydrate and inhibit bacterial growth.
   

5. Lysozyme (antibacterial) - An enzyme present in sweat that breaks down bacterial cell walls, particularly effective against Gram-positive bacteria.

Name 3 Acidic Environments as Chemical Defenses.

1. HCl in stomach - The acidic gastric environment kills many pathogens ingested with food.
   

2. Fatty acids in sebum (skin) - These create an acidic environment on the skin's surface.
   

3. Acidic vagina (from normal flora) - Lactic acid produced by lactobacilli maintains low pH, inhibiting the growth of pathogens.

What is Lysozyme?

Lysozyme is an enzyme found in tears, perspiration, and saliva that catalyzes the hydrolysis of bacterial cell walls, making it especially effective against Gram-positive bacteria.

Explain the action of the Mucociliary Escalator.

The Mucociliary Escalator is a defense mechanism of the respiratory system where mucus traps inhaled bacteria and dust particles, and cilia on epithelial cells move this mucus upward to be expelled or swallowed.

Where is the Mucociliary Escalator found?

The Mucociliary Escalator is located in the lining of the respiratory tract, particularly the trachea and bronchi, where ciliated columnar epithelium is present.

Identify the action of Transferrin.

Transferrin is a glycoprotein that binds iron in blood plasma, saliva, tears, and milk, thereby reducing the availability of iron for bacterial metabolism, which helps limit bacterial growth.

What is the function of Hydrochloric Acid (HCl)?

Hydrochloric Acid (HCl) is secreted by the stomach and serves a dual purpose: it aids in the digestion of food and also acts as a barrier against pathogens that are ingested.

What are Bile Salts?

Bile salts are bile acids that have been conjugated with amino acids, produced by the liver, and they play a key role in lipid digestion and can also inhibit the growth of certain bacteria.

Name a Bacterial Species Tolerant of Bile Salts.

Bacterial species such as Enterococcus faecalis and Streptococcus bovis are known to tolerate and grow in the presence of bile salts.

Explain 'iron withholding' and the antibacterial properties of transferrin.

Iron withholding refers to the mechanism by which transferrin binds iron, making it inaccessible for pathogenic bacteria, thus inhibiting their growth. Additionally, transferrin binds to lipopolysaccharides in the outer membrane of Gram-negative bacteria, disrupting their membrane integrity.

Explain the antiviral properties of transferrin/lactotransferrin.

Transferrin and lactotransferrin can inhibit viral infections by binding to lipoproteins on human plasma membranes, thereby preventing viruses that use these proteins as receptor sites from entering and infecting the cells.

Why could taking an iron supplement increase your risk for bacterial infections?

Taking iron supplements can lead to excess iron in the bloodstream, which may surpass the binding capacity of transferrin. This results in free iron becoming available, which can support the growth of pathogenic bacteria.

List 7 examples of mechanical defenses.

1. Diarrhea - Expels pathogens from the digestive tract.
   

2. Vomiting - Forces the evacuation of pathogens from the stomach.
   

3. Coughing - Clears the respiratory tract of irritants and pathogens.
   

4. Sneezing - Expels airborne pathogens from the nasal passages.
   

5. Urination - Flushes out pathogens from the urinary system.
   

6. Lacrimation - Tears wash away irritants and pathogens from the eyes.
   

7. Salivation - Saliva contains enzymes and antibodies that neutralize pathogens.
   

8. Sloughing/desquamation of the skin - Shedding of dead skin cells removes pathogen-laden cells.
   

9. Mucociliary escalator - Moves mucus trapping pathogens out of the respiratory tract.

How can urine serve as a mechanical defense?

Urine serves as a mechanical defense by its flow through the urinary tract, which helps dislodge and flush out bacteria, preventing urinary tract infections.

How do normal flora defend against pathogenic bacterial species?

1) Normal flora bacteria outcompete foreign pathogens for space and essential nutrients necessary for survival.

2) Normal flora produce bacteriocins or antibiotics that inhibit the growth of competing microbial species.

3) Normal flora create hostile environments for pathogens through mechanisms such as microbial antagonism, where the metabolic by-products (like acids) lower pH and deter pathogen colonization.

Describe what is meant by a body’s '2nd line of defense.'

The body's second line of defense includes immune responses that are activated when pathogens breach the first line of defense. These defenses are nonspecific and include components such as phagocytic cells, inflammation, fever, and the release of various chemical mediators to combat infections.

What is another name for granules carried by leukocytes?

Granules carried by leukocytes are also referred to as vesicles or sacs, which contain various bioactive compounds essential for the immune response.

What does it mean when leukocytes “degranulate”?

When leukocytes 'degranulate,' it refers to the process by which the contents of their granules (or vesicles) are released from the cell into the extracellular space through the mechanism of exocytosis. This release plays a crucial role in immune responses such as inflammation and combating infections.

List and briefly describe the 5 phases of phagocytosis (CAIDE).

1. Chemotaxis - This is the process of chemical attraction of phagocytes to a particular site of infection, driven by chemotactic chemicals such as bacterial toxins, components of damaged cells, complement proteins, and antibodies that mark pathogens for destruction.
   

2. Adherence or Attachment - In this phase, phagocytes attach to the pathogen's surface. This can be hindered by certain microbial defenses, such as the production of M proteins or slippery capsules. The process of opsonization, where microorganisms are coated with complement proteins or antibodies, facilitates this adherence, making it easier for phagocytes to recognize and engulf them.
   

3. Ingestion - The phagocyte then engulfs the microbe by extending its plasma membrane around it, resulting in the formation of a vesicle that contains the microbe.
   

4. Digestion - The vesicle containing the microbe fuses with a lysosome—a special intracellular vesicle packed with various digestive enzymes—allowing the breakdown of the microbe's components.
   

5. Exocytosis - After the microbe has been digested, the leftover debris is expelled from the phagocyte through exocytosis, clearing the cell of unwanted materials.

What compounds are contained in a lysosome?

Lysosomes contain digestive enzymes, specifically lysozymes, that break down various macromolecules, as well as reactive chemicals like hydrogen peroxide, hypochlorite, hydroxide ions, and free radicals such as superoxide, which assist in destroying engulfed pathogens.

Define chemotaxis.

Chemotaxis is the process whereby leukocytes are chemically attracted to the site of infection, a mechanism vital for the effective targeting of immune responses against pathogens.

What compounds can be chemotactic for phagocytes?

Chemotactic factors for phagocytes include complement proteins, bacterial toxins, antibodies, and components released from damaged tissue cells, all of which guide phagocytes to the site of infection.

What is the process of coating microbes with complement proteins or antibodies to facilitate phagocytosis called?

The process of coating microbes with complement proteins or antibodies to enhance phagocytosis is called opsonization, which increases the efficiency with which phagocytes can identify and engulf pathogens.

Name 2 opsonins.

Two types of opsonins are: 1) Complement proteins, which are part of the nonspecific immune response. 2) Antibodies, which are part of the specific immune response, marking pathogens for destruction by immune cells.

Name 2 structures on the surface of bacteria that can inhibit the adherence step of phagocytosis.

Two structures that can hinder the adherence of phagocytes to bacteria are capsules and M proteins found on fimbriae, which can interfere with phagocyte attachment and subsequent engulfment.

What bacterial species inhibits the digestion step of phagocytosis, allowing it to survive inside of a macrophage?

Mycobacterium tuberculosis is known to inhibit the digestion step of phagocytosis, enabling it to evade destruction and persist within macrophages.

What structure would help a bacterial cell outrun a phagocyte and escape phagocytosis?

Flagella are motility structures that can enable a bacterial cell to swim away from phagocytes, thereby facilitating its escape from phagocytosis.

What enzyme is produced by Staphylococcus aureus to kill white blood cells?

Staphylococcus aureus produces leukocidins, which are toxins specifically designed to kill white blood cells and impair the immune response.

How does coagulase enzyme protect bacteria from phagocytosis?

The coagulase enzyme triggers the formation of blood clots, allowing bacteria to multiply within these clots and remain hidden from the immune response by evading phagocytosis. Additionally, bacteria can coat themselves with fibrin, further preventing phagocytosis.

What is the technical term for fever?

The technical term for fever is pyrexia, which refers to an increase in body temperature as a part of the immune response.

What triggers of fever are called?

Triggers that induce fever are known as pyrogens, which can originate from both external and internal sources.

What are exogenous and endogenous pyrogens?

Exogenous pyrogens are substances, like lipopolysaccharides released from Gram-negative bacteria, that provoke fever from outside the body. Endogenous pyrogens are produced internally, such as interleukins, interferons, and Tumor Necrosis Factor (TNF), which are released by activated immune cells during an immune response.

What is the body’s thermostat?

The hypothalamus is the body's thermostat, regulating body temperature by coordinating responses to maintain homeostasis.

How do pyrogens like interleukins induce fever?

Pyrogens such as interleukin travel to the hypothalamus and stimulate its production of prostaglandins, which reset the hypothalamic thermostat to a higher temperature, resulting in fever.

What compound is involved in resetting the hypothalamus at a higher temperature?

Prostaglandins are the compounds that facilitate the resetting of the hypothalamic thermostat, tricking the body into raising its temperature to fight infections.

What 3 mechanisms in the body act to increase body temperature?

1. Vasoconstriction - Blood vessels to the skin and extremities constrict to reduce heat loss, thereby conserving body heat.
   

2. Shivering/Chills - Vasoconstriction causes skin to cool, triggering skeletal muscle contractions and the contraction of arrector pili muscles to produce heat (goosebumps).
   

3. Increased Thyroid Hormones - The thyroid gland enhances the production of thyroid hormones, boosting metabolic rate and generating heat through chemical reactions in the body.

Why are low-grade fevers beneficial?

Low-grade fevers inhibit the growth of certain microbes since many bacteria are mesophilic rather than thermophilic. Additionally, increased body temperature enhances heart rate, accelerating the delivery of immune cells to infection sites, stimulates B and T cell proliferation, and speeds up biochemical reactions, promoting more efficient immune responses.

Why are high-grade fevers harmful?

High-grade fevers can be detrimental because they risk denaturing the body’s own proteins and enzymes, leading to cellular dysfunction and potentially severe health consequences.

What percentage of children experience febrile seizures?

Approximately 3-5% of children experience febrile seizures, which are convulsions associated with fever.

True or False: Febrile seizures are scary because they can cause brain damage.

False. While febrile seizures can be alarming to witness, they generally do not cause brain damage and are often benign.

Consider the following: Two children are both three years old. Johnny weighs 50 pounds; Tammy weighs only 30. The children are approximately the same height. Which child can tolerate a higher fever? Why?

Tammy can tolerate a higher fever because she has a higher surface area-to-volume ratio, which allows her body to dissipate heat more effectively to the environment, reducing the risk of overheating.

Why can children generally tolerate higher fever than adults?

Children have a higher surface area-to-volume (SA/V) ratio, which allows them to dissipate heat to the environment more efficiently than adults, thus enabling them to manage higher fevers without as many adverse effects.

What is the action of fever reducers/pain relievers such as acetaminophen & ibuprofen?

Fever reducers like acetaminophen and ibuprofen work by inhibiting the synthesis or release of prostaglandins, which are compounds involved in the fever response and pain sensation, thus lowering temperature and alleviating discomfort.

Why is it not a good idea to administer a fever reducer for a low-grade fever?

Administering a fever reducer for a low-grade fever can mask symptoms of illness. Lowering the fever may make children feel better, causing them to play and expend energy that is better spent on fighting the infection and healing. Consequently, reducing a fever can allow pathogens to proliferate, potentially leading to a higher fever once the medication is stopped.

Why might it not be a good idea to give a cool bath to someone with a fever?

Giving a cool bath to someone with a fever can lead to chills as the body tries to generate more heat in response to being cooled. This physiological response can cause skeletal muscle contractions that produce even more heat, potentially increasing the body temperature further.

What kind of leukocyte is a Natural Killer (NK) cell?

A Natural Killer (NK) cell is a type of lymphocyte, which is a white blood cell involved in the innate immune response.

How is a NK cell different from B and T lymphocytes?

Natural Killer (NK) cells differ from B and T lymphocytes in that they do not possess antibodies (like B cells) or antigen receptors (like T cells); instead, they can recognize stressed, infected, or tumor cells without the need for these specific markers.

What are NK cells looking for on the surface of cells?

Natural Killer (NK) cells are looking for 'self markers' known as MHC class I markers, which are typically present on healthy human cells to indicate their normal status to the immune system.

What is self-tolerance?

Self-tolerance is the ability of leukocytes to distinguish between the body's own cells (self) and foreign cells (non-self), preventing an autoimmune response where the immune system attacks its own tissues.

What are 'self markers' called?

Self markers are referred to as MHC class I markers, where MHC stands for Major Histocompatibility Complex, a set of molecules displayed on cell surfaces that help the immune system recognize self from non-self.

How do NK cells kill their targets?

Natural Killer (NK) cells kill their targets by detecting the absence or reduced presence of MHC class I markers on infected or abnormal cells. When these markers are not sufficiently expressed, NK cells degranulate—releasing cytotoxic granules containing perforins and proteases. Perforins form pores in the target cell's plasma membrane, allowing proteases to enter and induce apoptosis, a programmed form of cell death that minimizes inflammation and damage to surrounding tissues.

Why would a NK cell attack a viral infected human cell?

NK cells can target viral-infected human cells because many viruses induce the infected cells to downregulate or decrease the production of MHC class I markers on their surface. Fewer MHC class I markers can signal to NK cells that the cell is abnormal and should be destroyed, allowing NK cells to effectively identify and eliminate potentially harmful cells, even those that exhibit some level of normalcy.

Why are cancer/tumor cells targets of NK cells?

Cancer cells often downregulate MHC class I markers in a similar way to viral-infected cells, making them less detectable by the immune system. NK cells are then capable of recognizing the low levels of MHC class I markers and targeting these cancerous cells for destruction, thus playing a crucial role in immune surveillance against tumors.

What does NET stand for?

NET stands for Neutrophil Extracellular Traps, which are web-like structures that trap and kill pathogens.

NETs are produced by what type of leukocyte?

NETs are produced by neutrophils, a type of white blood cell crucial for the immune response to infection.

Explain how these leukocytes commit suicide to form NETS.

When neutrophils are activated, they undergo a process of suicide called NETosis. During this process, they expel the contents of their nuclei, which includes DNA and bactericidal enzymes, creating a mesh-like structure called a NET. This trap captures invading bacteria and fungi, effectively immobilizing and killing them in the extracellular space.

What cells produce complement proteins?

Most complement proteins are synthesized by hepatocytes (liver cells), although they can also be produced by other cells, including macrophages and epithelial cells.

What analogy is used to describe the cascade pathway of the complement system? Why is this analogy used?

The cascade pathway of the complement system is often described using the domino analogy. Once one complement protein is activated, it triggers the activation of subsequent proteins in the pathway, much like how knocking down one domino leads to the sequential fall of many others. This analogy illustrates the highly coordinated and amplifying nature of the complement system activation process.

What activates the complement system?

1) Classical pathway – This pathway is activated when an antibody binds to its specific antigen, resulting in the fixing and activation of complement proteins.

2) Alternative pathway – Activated directly by the presence of certain microbial surfaces, such as carbohydrates and lipopolysaccharides found in bacterial membranes.

3) Lectin pathway – Activated by mannose-binding lectin (MBL) binding to specific carbohydrates on the surface of pathogens.

List the 4 functions of the complement system. (COLA)

The four primary functions of the complement system are: 1) Chemotaxis – Attracting immune cells to sites of infection.

2) Opsonization – Coating pathogens to enhance phagocytosis by immune cells.

3) Lysis – Destroying pathogens by puncturing their membranes via membrane attack complexes (MAC).

4) Activation of inflammatory responses – Promoting inflammation to help recruit and activate other immune components.

What forms membrane attack complexes (MAC) and what is their function?

Membrane attack complexes (MAC) are formed by complement proteins that assemble into a pore-like structure that punches holes in the cell membranes of pathogens, leading to cell lysis and death by allowing ions and water to freely enter and exit the bacterial cells.

What are the 4 major symptoms of inflammation?

The four major symptoms of inflammation are: 1) Redness – Due to increased blood flow to the area (vasodilation).

2) Swelling – Resulting from the accumulation of interstitial fluid due to increased vessel permeability.

3) Pain/Irritation – Caused by nerve fiber injury, pressure from swelling, and the release of inflammatory mediators like prostaglandins.

4) Heat – From increased metabolic activity in the inflamed tissue, resulting in higher local temperatures.

Explain the activation of the inflammatory response. What are the 3 ways mast cells are activated?

The inflammatory response is activated when tissue is damaged or infected. Mast cells can be activated through three mechanisms:

1) Pathogen binding to receptors on mast cells.

2) Binding of IgE antibodies to receptors on mast cells, which then attach to specific antigens.

3) Complement proteins binding to receptors on mast cells. Upon activation, mast cells degranulate, releasing histamine and other cytokines, leading to vasodilation and increased permeability of blood vessels, thereby facilitating an inflammatory response.

Blood vessels dilate and become 'leaky' due to the release of histamine by basophils and mast cells. What's the purpose?

The dilation and increased permeability of blood vessels aim to deliver more blood and its components, such as antibodies, white blood cells, and complement proteins, to the site of infection. This enhanced blood flow allows immune cells and proteins to exit the bloodstream and enter the interstitial spaces to combat pathogens effectively.

What compound is released from injured cells to affect pain receptors?

Prostaglandins are the compounds released from injured cells that sensitize pain receptors, contributing to the sensation of pain during inflammation.

Why do medications like acetaminophen reduce both fever and pain?

Medications such as acetaminophen are effective in reducing both fever and pain because they inhibit prostaglandin synthesis and release. Since prostaglandins play a key role in both fever regulation and pain sensation, their inhibition provides symptomatic relief.

Define diapedesis.

Diapedesis is the process by which white blood cells (leukocytes) move out of the bloodstream and into tissues by squeezing through the gaps between endothelial cells of blood vessel walls, allowing them to reach sites of infection or injury.

How do white blood cells move through tiny tissue spaces?

White blood cells move through tiny tissue spaces utilizing a mechanism known as amoeboid movement. This movement enables them to alter their shape and squeeze between the endothelial cells in blood vessel walls, allowing them to navigate through interstitial spaces to reach sites of infection or injury.

What is pus?

Pus is a thick fluid that accumulates at sites of inflammation and infection, primarily composed of dead leukocytes (often neutrophils), cellular debris, and pathogens, indicating the body's immune response to an ongoing infection.

What component of blood is involved in the clotting mechanism?

Platelets are the specific components of blood that play a key role in the clotting mechanism. They aggregate at injury sites to form a clot, serving to contain pathogens and prevent their spread to surrounding healthy tissues.

What is the cause of each of the following?

1) Redness – due to large amounts of blood flowing through tissues as a result of vasodilation.

2) Heat – due to increased metabolic activity and chemical reactions producing additional heat.

3) Pain/Irritation – can be caused by injury to nerve fibers, bacterial toxins, swelling exerting pressure on nerve endings, and the release of inflammatory mediators like prostaglandins.

4) Swelling – arises from increased interstitial fluid due to leaky blood vessels (arterioles), resulting in more plasma leaving circulation and entering tissues.

What can happen when the inflammatory response is not controlled?

When the inflammatory response is not controlled, it can lead to chronic inflammation, damaging healthy cells, tissues, and organs, resulting in conditions such as scarring and tissue death. Moreover, chronic inflammation is associated with increased risks of developing autoimmune diseases and cancer, as prolonged swelling and edema can impede blood flow and heighten susceptibility to secondary infections.

Sodium chloride in sweat

Chemical

Transferrin in body fluids

Chemical

Diarrhea

Mechanical

Vomiting

Mechanical

Skin shedding

Mechanical

Bile salts

Chemical

Hydrochloric acid in stomach

Chemical

Tears

Mechanical

Saliva

Chemical

Lysozyme in bodily fluids

Chemical

Urine

Mechanical

Mucociliary escalator

Mechanical

Fatty acids in sebum

Chemical

Stratified squamous epithelium

Structural

Keratin in skin cells

Structural

Coughing

Mechanical

Sneezing

Mechanical

Release histamine; circulate in the blood

Basophil (d)

Major phagocytes

Macrophages, Eosinophils, Neutrophils (a, b, c)

Involved in inflammatory and allergic responses

Basophils, Mast cells (d, f)

3 types are T cells, B cells, and NK cells

Lymphocytes (e)

Active during parasitic infections (helminths)

Eosinophils (b)

Some are fixed, some are wandering

Macrophages (a)

“Bacteria slayers”

Neutrophils (c)