Self-Recognition and the Human Immune System
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Questions and Answers

The human immune system distinguishes between "self" and "nonself" primarily to:

  • Regulate hormonal imbalances and maintain homeostasis within the endocrine system.
  • Target and neutralize threats while preserving the body's own tissues. (correct)
  • Produce antibodies against all foreign substances encountered irrespective of their harmfulness.
  • Initiate fever responses to elevate body temperature and inhibit microbial growth.

Which of the following is a critical distinction between the innate and adaptive immune systems' receptors?

  • Adaptive immune receptors are limited in number and fixed, while innate receptors offer enormous diversity through gene rearrangement.
  • Adaptive immune receptors are passed down through generations identically, while innate receptors are generated somatically.
  • Innate immune receptors are encoded in the genome, while adaptive receptors are generated through somatic gene rearrangement. (correct)
  • Innate immune receptors recognize specific antigens, while adaptive receptors recognize broad molecular patterns.

The process of V(D)J recombination in adaptive immunity directly contributes to:

  • The rapid, non-specific response characteristic of the innate immune system.
  • The limited recognition of common microbial molecular structures.
  • The generation of an enormous diversity of antigen receptors on lymphocytes. (correct)
  • The prevention of autoimmune reactions by ensuring self-tolerance.

Why is the adaptive immune system more capable of recognizing a wider array of antigens compared to the innate immune system?

<p>Because the adaptive immune system utilizes somatic gene rearrangement to create a vast repertoire of receptors. (A)</p> Signup and view all the answers

What is the primary reason the innate immune system responds more rapidly to pathogens than the adaptive immune system?

<p>Innate immune cells are pre-programmed to recognize common molecular patterns, allowing for immediate action. (D)</p> Signup and view all the answers

Which of the following mechanisms do natural killer (NK) cells use to identify and target abnormal host cells for destruction?

<p>Detection of reduced or absent expression of MHC class I molecules on the cell surface. (A)</p> Signup and view all the answers

What is the immunological relevance of 'self' recognition in the context of transplanted tissues?

<p>Recognition of self-structures triggers a regulatory response that prevents over-activation of immune cells. (B)</p> Signup and view all the answers

How does the adaptive immune system develop immunological memory?

<p>By modifying its responses to frequently encountered substances. (B)</p> Signup and view all the answers

What is the impact of immunologic memory on subsequent encounters with the same pathogen?

<p>Subsequent responses are faster and more vigorous. (D)</p> Signup and view all the answers

Which of the following best describes how microbes might utilize molecular mimicry to evade host immune responses?

<p>By altering their surface antigens to resemble host molecules, thus preventing immune recognition. (D)</p> Signup and view all the answers

How does the coating of microbes with host proteins such as fibrin contribute to immune evasion?

<p>By masking unique microbial antigens, thus preventing recognition by the immune system. (C)</p> Signup and view all the answers

Which of the following reflects the purpose of receptors in the immune system for self versus non-self recognition?

<p>Receptors function to initiate apoptosis in all cells encountered to prevent infection. (B)</p> Signup and view all the answers

Which of the following mechanisms primarily contributes to the long-lasting protection associated with active immunity compared to passive immunity?

<p>Passive immunity involves the administration of preformed antibodies, providing immediate but temporary protection. (B)</p> Signup and view all the answers

A patient who has received passive antibody therapy is at risk of which of the following complications?

<p>A decreased level of protection due to short-term protection (C), Hypersensitivity reaction due to consistent exposure. (D)</p> Signup and view all the answers

What is a key distinction between acquired active and acquired passive immunity?

<p>Acquired passive immunity elicits a rapid and robust immune response that continues indefinitely. (C)</p> Signup and view all the answers

How do tears protect the body from external adverse influencers?

<p>By secreting soluble IgA, lysozymes, and other enzymes such as lactoferrin and lipocallin that hydrolyze the cell wall of bacteria and create tears, leading to cell lysis. (C)</p> Signup and view all the answers

What is the primary function of mucins as a chemical barrier in the body?

<p>By creating a mucus layer on mucosal surface that acts as a gel-like barrier that traps microbes and prevents them from reaching the epithelial cells. (B)</p> Signup and view all the answers

Why are patients that are prescribed antibiotics more susceptible to vaginal candidiasis?

<p>Antibiotics consumption disrupt normal bacterial flora allowing fungi to overgrow, leading to the development of vaginal candidiasis. (C)</p> Signup and view all the answers

Which of the following characteristics distinguishes the innate immune system's response from that of the adaptive immune system?

<p>The innate immune response is immediate and identical despite multiple infections. (D)</p> Signup and view all the answers

How does the innate immune system recognize pathogens?

<p>By the limited number of pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs). (C)</p> Signup and view all the answers

How do pattern recognition receptors (PRRs) discriminate between self and nonself?

<p>By binding to molecules widely expressed by microbes but absent from the host. (D)</p> Signup and view all the answers

What is the role of opsonins in the innate immune response?

<p>To activate complement cascades independently of antibody involvement. (D)</p> Signup and view all the answers

In the complement system, what is the role of C3b?

<p>It serves as an opsonin, tagging pathogens for phagocytosis. (C)</p> Signup and view all the answers

What is the function of anaphylatoxins (C3a, C4a, C5a) in the complement system?

<p>They generate a localized inflammatory, cellular recruitment, and vascular permeability response. (C)</p> Signup and view all the answers

How does the lectin pathway contribute to the activation of the complement system?

<p>By recognizing mannose-containing residues on the surfaces of microbes. (A)</p> Signup and view all the answers

Regarding the complement pathways, what is the function of c3b?

<p>Promotes opsonization, effectively tags the bacteria for phagocytic cells to identify, attach and engulf bacteria. (C)</p> Signup and view all the answers

How can pyogenic infections provide insight regarding a C3 deficiencies?

<p>A patient with a C3 deficiency can develop immunity to pyogenic infections through over exposure. (D)</p> Signup and view all the answers

A key mechanism of dendritic cells engulf tissues to remove pathogens involves:

<p>Macropinocytosis. (A)</p> Signup and view all the answers

If a patient begins to show an increased number of peripheral blood neutrophils, what is the most likely clinical indication?

<p>Acute infection. (B)</p> Signup and view all the answers

Which aspect of neutrophils contributes mostly to the rapid and effective killing of the pathogens at the site of infection?

<p>Bacterial lysis. (C)</p> Signup and view all the answers

In the context of immune responses, what key advantage do somatically generated receptors provide over pattern recognition receptors (PRRs)?

<p>Enhanced ability to recognize an almost limitless diversity of antigens, including novel ones. (B)</p> Signup and view all the answers

How does the adaptive immune system's immunologic memory differ fundamentally from the innate immune system's response?

<p>Adaptive immunity responds more quickly upon initial encounter, whereas innate is slower. (B)</p> Signup and view all the answers

Which of the following mechanisms enables NK cells to recognize and target cells that lack 'self' markers?

<p>Detecting reduced levels or absence of MHC class I molecules on the cell surface. (B)</p> Signup and view all the answers

Why is the skin's stratum corneum considered a critical mechanical barrier against infection?

<p>It is composed of tightly layered, dead cells providing a dry and impermeable barrier. (A)</p> Signup and view all the answers

Chronic smokers are at increased risk of respiratory infections because smoking impairs which protective mechanism?

<p>The rhythmically beating cilia that clear secretions from the respiratory tract. (B)</p> Signup and view all the answers

How does the acidic environment of the stomach contribute to the body's chemical defense against pathogens?

<p>By inhibiting the growth and colonization of ingested microbes within the gastrointestinal tract. (C)</p> Signup and view all the answers

Microcidal molecules like defensins and cathelicidin provide protection by:

<p>Enhancing the replication rate of commensal microbes. (B)</p> Signup and view all the answers

How do tears contribute to the chemical defense of the eyes?

<p>Lysozyme degrades bacterial cell walls. (C)</p> Signup and view all the answers

What is the function of goblet cells in the mucous membranes?

<p>Facilitating the exchange of molecules with the environment. (D)</p> Signup and view all the answers

Which of the following is a key distinction between acquired active and acquired passive immunity?

<p>Acquired active immunity is short-lived, whereas passive immunity provides long-lasting protection. (B)</p> Signup and view all the answers

What is a major risk associated with passive antibody therapy, such as intravenous immunoglobulin (IVIG)?

<p>Increased susceptibility to bacterial infections due to complement consumption. (B)</p> Signup and view all the answers

Why does active immunity generally provide longer-lasting protection compared to passive immunity?

<p>Passive immunity directly depletes the recipient's pre-existing immune cells. (B)</p> Signup and view all the answers

A microbe coats itself with host proteins, specifically fibrin. How might this contribute to immune evasion?

<p>Mimicking 'self' and avoiding recognition by immune cells. (D)</p> Signup and view all the answers

When the initial mechanical barriers of the body are breached, what is the first immunologic line of defense?

<p>Activation of B lymphocytes. (C)</p> Signup and view all the answers

Which statement most accurately describes how the innate immune system recognizes pathogens:

<p>(B)</p> Signup and view all the answers

How do pattern recognition receptors (PRRs) distinguish between self and nonself molecules?

<p>(B)</p> Signup and view all the answers

What role do opsonins play in the innate immune response?

<p>Directly neutralizing toxins produced by pathogens. (C)</p> Signup and view all the answers

Which of the following best describes the role of C3b in the complement system:

<p>It forms the membrane attack complex (MAC). (C)</p> Signup and view all the answers

What is the primary function of anaphylatoxins (C3a, C4a, C5a) in the complement system?

<p>Attracting and activating leukocytes to promote inflammation. (C)</p> Signup and view all the answers

How does mannan-binding lectin (MBL) initiate the lectin pathway of complement activation?

<p>By cleaving C3 into C3a and C3b. (C)</p> Signup and view all the answers

Which of the following statements is true regarding C3 deficiencies?

<p>C3 deficiencies result in impaired T cell function and autoimmunity. (C)</p> Signup and view all the answers

Pluripotent hematopoietic stem cells are the originating cell line for all blood cellular components. Which of the following best describes the role of these cells?

<p>They give rise to all leukocytes, erythrocytes, and platelets. (B)</p> Signup and view all the answers

How do tissue macrophages respond to pathogens upon recognition?

<p>(C)</p> Signup and view all the answers

What is the critical role of monocytes compared to macrophages in the immune response?

<p>Monocytes differentiate into tissue macrophages and actively sample for invading pathogens. (C)</p> Signup and view all the answers

In a patient with urothelial cancer that lacks MHC class 1 antigen on their surface, which recombinant cytokine could be injected into this solid tumor to increase this tumor cell’s susceptibility to CD8+ mediated killing?

<p>TNF-α (E)</p> Signup and view all the answers

Which of the following best describes the reason why a 30-year-old female developed vaginal candidiasis (a fungal infection) after receiving antibiotic therapy for a sinus infection

<p>Antibiotic-induced disturbances to mucus secretions (C)</p> Signup and view all the answers

Which complement pathway is activated by antigen that leads to antibody complexes, bridge from innate to adaptive immunity

<p>Alternative pathway (D)</p> Signup and view all the answers

An elderly alcoholic man is brought to the emergency department after a difficult night during which his incessant coughing kept him from sleeping. Diagnostics of his serum contained high titers of IgM antibodies specific for S. pneumoniae capsule. What is the complement mechanism most likely to act in concert with this early IgM production to clear infection?

<p>LAK cells (C)</p> Signup and view all the answers

All of the following structures are found in tears EXCEPT:

<p>lysozyme (B)</p> Signup and view all the answers

What is the function of Mucins in protecting the body?

<p>Triggering inflammation (D)</p> Signup and view all the answers

How might microbes "defend" against host recognition of non-self?

<p>Molecular mimicry (D)</p> Signup and view all the answers

A key mechanism of dendritic cells engulfing of tissues to remove pathogens involves:

<p>Secreting large amounts of complement proteins. (E)</p> Signup and view all the answers

The role of the complement C3 for all three complement pathways include all of the following Except:

<p>Spontaneous hydrolysis. (A)</p> Signup and view all the answers

What can pyogenic infections tell you about the patient?

<p>(D)</p> Signup and view all the answers

Which of the following cell types are notable for their presence at the sites of helminth infections

<p>Basophils (A)</p> Signup and view all the answers

Choose the description below that reflects the function of pluripotent hematopoietic stem cells

<p>Undergo further differentiation within thymus (C)</p> Signup and view all the answers

If an individual lacks the ability to produce somatically generated receptors, which immune function would be most directly impaired?

<p>Formation of immunological memory against specific antigens. (C)</p> Signup and view all the answers

In a scenario where a novel pathogen emerges, which aspect of the adaptive immune system is MOST crucial for initiating an effective immune response?

<p>The fixed set of pattern recognition receptors recognizing conserved microbial structures. (C)</p> Signup and view all the answers

Why is the skin considered such a critical barrier?

<p>It contains oil and sweat glands (sebaceous and sudoriferous glands, respectively), some of whose products are slightly acidic. (D)</p> Signup and view all the answers

A patient with cystic fibrosis experiences recurrent respiratory infections because of:

<p>An abnormally thickened and viscous mucus that impairs mucociliary clearance. (C)</p> Signup and view all the answers

How would the loss of MHC class I expression on a cell affect its interactions with the immune system?

<p>It would enhance its recognition and killing by cytotoxic T cells. (C)</p> Signup and view all the answers

Which immune mechanism would be MOST effective against a virus that actively suppresses MHC class I expression in infected cells?

<p>Natural killer (NK) cell-mediated cytotoxicity. (D)</p> Signup and view all the answers

Which of the following best explains why commensal bacteria are considered a biological barrier?

<p>They directly stimulate the adaptive immune system. (C)</p> Signup and view all the answers

How does the human body reduce the possibility of infection from external influences?

<p>Tears contain natural enzymes like lysozymes that hydrolyze the cell wall of bacteria and creates cell lysis. (D)</p> Signup and view all the answers

Why is the acidic pH of the stomach crucial for preventing infections?

<p>It degrades antibodies ingested with food. (D)</p> Signup and view all the answers

Following burn trauma, patients are highly susceptible to bacterial infections because of a compromised:

<p>Function of the complement system. (C)</p> Signup and view all the answers

A researcher discovers a novel bacterial strain that is resistant to phagocytosis. Which strategy would MOST likely enhance the immune response against this bacterium?

<p>Inhibiting the production of cytokines by macrophages. (B)</p> Signup and view all the answers

How does C3b enhance the innate immune response?

<p>It directly lyses bacterial cells. (C)</p> Signup and view all the answers

What outcome would likely happen if a patient suffers from C3 deficiencies?

<p>Impaired antibody production. (C)</p> Signup and view all the answers

What is the major role of anaphylatoxins, such as C5a, in the innate immune response?

<p>Inhibiting complement activation. (B)</p> Signup and view all the answers

How does the mannose-binding lectin (MBL) pathway activate the complement system?

<p>By activating natural killer cells. (C)</p> Signup and view all the answers

Why deficiency in C9 poses the least risk?

<p>Alternative pathways are activated through spontaneous hydrolysis of c3. (D)</p> Signup and view all the answers

When a phagocyte engulfs a pathogen, what is the fate of the engulfed microbe?

<p>It multiplies rapidly within the phagosome. (C)</p> Signup and view all the answers

Where does the process of pluripotent hematopoietic stem cell production occur?

<p>Thymus. (D)</p> Signup and view all the answers

What is the primary role of monocytes in the immune response?

<p>To kill virus-infected cells. (C)</p> Signup and view all the answers

In the context of innate immunity, what distinguishes dendritic cells from macrophages?

<p>Macrophages cannot produce cytokines, whereas this is the primary function of Dendritic cells. (B)</p> Signup and view all the answers

Flashcards

Human Immune System

Defensive mechanisms that identify and neutralize threats to the human body, distinguishing 'nonself' from 'self'.

First Line of Defense

Mechanical (e.g., skin), chemical (e.g., stomach acid), and biologic (e.g., commensal microbes) barriers that protect the body from external threats.

Protective Systems

The second and third lines of defense activated when barriers are breached; includes the innate and adaptive immune systems.

Threats to the Body

An organism or agent that poses a risk to the body's health, potentially causing disease.

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Commensal Microbes

Microorganisms that live in or on a host organism without causing harm, often part of the normal microbiota.

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Pattern Recognition Receptors (PRRs)

Encoded directly in the genome, these receptors are limited and recognize common molecular structures found in microbes but not in human cells.

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Pathogen-Associated Molecular Patterns (PAMPs)

Common molecular structures found in many microbes but not in human cells, recognized by PRRs.

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Somatically Generated Receptors

Receptors generated through somatic gene rearrangement, providing enormous variety to recognize virtually any antigen.

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V(D)J Recombination

Random assembly of gene segments (Variable, Diversity, Joining) encoding receptors, adding diversity during recombination.

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Receptor Vetting

Process where receptors are uniquely vetted, retaining a set of receptors individualized to that particular self and nonself environment.

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Immunologic Memory

The ability to modify the immune response to substances encountered on multiple occasions, distinguishing the adaptive from the innate immune system.

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Innate Receptors

Evolutionarily conserved receptors offering reliability against common pathogens.

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Adaptive Receptors

Evolutionarily flexible receptors allowing the immune system to adapt to new or mutating pathogens.

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MHC Class I Molecules

Cell-surface molecules present on every normal nucleated cell of the body, used by natural killer cells to determine if a cell is 'self'.

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Pattern Recognition Receptors (PRRs)

Receptors designed to recognize and bind to nonself structures abundant in the microbial world but not typically expressed in normal host cells.

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Immune System Approaches

Elimination of threats by isolating, disrupting, or ingesting and consuming them.

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Pattern Recognition Receptors (PRRs)

Genetically determined receptors that bind to molecules widely expressed by microbes but not by host cells.

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Immunologic Memory

Rapid and vigorous immune responses to speedily eliminate microbes, often before their presence can be detected by other means.

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Microbe (Microorganism)

A microscopic organism, including bacteria, viruses, fungi, protozoa, algae, and archae.

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Cytokines

Proteins including interferon, interleukins, and growth factors secreted by leukocytes and other cells and are involved in immunity and inflammation.

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Chemokines

A subgroup of cytokines involved in the chemical-induced migration or chemotaxis of leukocytes.

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Anaphylatoxins

Substances derived from complement activation that trigger release of inflammatory mediators and cause contraction of smooth muscles and leakage from capillaries.

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Opsonins

Molecules that, when attached to the surface of microbes, make them more attractive to phagocytic cells, facilitating microbe destruction.

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Tolerance of Immune System

When a host’s immune system reduces its response to a specific antigen because it becomes 'used to' or overwhelmed by it.

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Molecular Mimicry

The microbe's antigens look very similar to the host’s own proteins (antigens).

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Air turbulence via nostril hairs

Air turbulence caused by hairs within the nostrils deposits particles larger than 10 mm in the nasal mucosa

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Cystic Fibrosis

A process that leads to abnormally thickened and viscous secretions that can obstruct the respiratory tract.

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Acidic pH

The acidic pH of the skin, stomach, and vagina serves as a chemical barrier against microbes.

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Antimicrobial Peptides

The skin is protected by several antimicrobial peptides secreted by various cell types and molecules secreted can inhibit or even kill microbes that are attempting to colonize

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Toll-like Receptors (TLRs)

Receptors that mediate recognition of diverse pathogens. After binding to PAMPs, signal transduction from a TLR to the nucleus leads to enhanced activation of genes encoding cytokines and other molecules involved in antimicrobial activity

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Complement

Enzymes and proteins functioning in both innate and adaptive branches of the immune system as a soluble means of protection against pathogens that evade cellular contact

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Anaphlotoxins

Cytokines that attract and activate different types of leukocytes and draw additional cells to the site of infection to help eliminate microbes.

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Soluble IgA

The body produces soluble IgA, lysozyme and other enzymes such as lactoferrin and lipocallin that hydrolyze the cell wall of bacteria and create tears, leading to cell lysis.

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Complement production

the liver, after initiation from a variety of inflammatory stimuli, complement proteins activate one another in a cascade manner.

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Degranulation

The process by which certain cells of the immune system release granules—small, pre-formed packets of bioactive molecules—into the extracellular environment.

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Chemotaxis and Inflammation

These signals involve a chemical gradient that immune cells detect through specialized receptors. The mechanism of chemotaxis involves that immune cells move directionally toward higher concentrations of the chemotaxin.

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Innate Immune Responses

Rapid, nonspecific responses to infection or injury including destruction of infectious organisms, activation of phagocytic cells, and the localized protective response known as inflammation

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Humoral Immunity

A branch of adaptive immunity mediated by B cells and their production of antibodies that target extracellular pathogens (bacteria, viruses outside cells, and toxins).

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Innate vs. Adaptive Immune Response

The first cellular line of defense provides immediate and identical immune response after multiple infections. Conversely, adaptive immunity improves and enhances over time and produces highly diverse antibodies

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Pluripotent Hematopoietic Stem Cells

Pluripotent hematopoietic stem cells originate from the bone marrow and serve as the ancestral cell line for all of the cells found in the blood. Phagocytes are differentiated by the presence of cytoplasmic granulation

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Granulocytes

White blood cells that have multilobed nuclei and contain conspicuous cytoplasmic granules.

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Agranular Leukocytes

White blood cells with a single, unlobed nucleus and cytoplasm that contains few or no granules.

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Innate Lymphoid Cells

Innate lymphoid cells respond to infected or injured tissues and release cytokines. Are commonly found in the skin, lungs and gastrointestinal tract.

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Neutrophils

The most numerous leukocyte population that are the first leukocytes recruited to infection and inflammation sites and are very effective at killing bacteria.

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Basophils

Acidic cytoplasmic granules that contain vasoactive amines (histamine) that cause smooth muscle contraction and are readily stained with “base-loving” dyes

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C3B tag for phagocytosis

Proteolytic enzymes lead to cell lysis and cell death. Complement is activated by three pathways in the body, and functions by opsonization with C3b tag cell for phagocytosis

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Comprising approximately 60% of the peripheral blood leukocytes

They are the most numerous leukocyte population. More than 100 billion enter the peripheral circulation daily in normal healthy adults in order to combact bacteria or viruses

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Lysozymes

Lysozymes break down peptidoglycan, a constituent of most bacterial cell walls. Also is produced in tears, therefore lacrimal glands aid in providing chemical barrier.

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Viral Interferons

Enzymes that degrade mRNA are activated and begin to break down virus and cellular genetic information. Natural killer cells produce interferon in response to non self antigens on the surface of cancerous cells

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Study Notes

Self-Recognition and the Human Immune System

  • The human body is constantly threatened by organisms and molecules.
  • The immune system defends by distinguishing "nonself" threats from "self."
  • Threats originate externally (infectious organisms, toxins) or internally (cancerous changes).
  • The immune system has three defense layers: mechanical, chemical, and biological barriers; the innate immune system; and the adaptive immune system.

Lines of Defense

  • First line: Mechanical, chemical, and biological barriers.
  • Second line: Innate immune system.
  • Third line: Adaptive immune system.

Innate vs. Adaptive Immune Systems

  • Both systems use cell-surface and soluble receptors to sense threats but differ in how the receptors are generated.

Innate Immune System

  • Utilizes a limited set of fixed receptors encoded in the genome.
  • Receptors recognize Pathogen-Associated Molecular Patterns (PAMPs) common in microbes but not human cells.
  • Examples of Pattern Recognition Receptors (PRRs): Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs).
  • Provides a broad, non-specific detection of pathogens due to the limited number of receptors.

Adaptive Immune System

  • Generates a vast array of receptors on B cells (antibodies) and T cells (T cell receptors, or TCRs) through somatic gene rearrangement.
  • Somatic gene rearrangement involves V(D)J Recombination (random assembly of gene segments) and Junctional Diversity (random nucleotide changes).
  • Recognizes virtually any antigen due to this diversity.
  • B cells and T cells generate distinct receptors through gene rearrangement.
  • Lymphocytes undergo a vetting process to retain receptors individualized to self and the nonself environment.
  • Displays immunologic memory, modifying responses to substances encountered multiple times.

Speed vs. Specificity

  • Innate Immune System: Quick response (minutes to hours), less specific, first line of defense.
  • Adaptive Immune System: Slower initial response (days), highly specific, provides long-term immunity.

Coverage

  • Innate: Detects a wide range of microbes using conserved patterns.
  • Adaptive: Recognizes highly specific antigens, even novel ones.

Evolutionary Trade-Off

  • Innate receptors: Evolutionarily conserved, reliable against common pathogens.
  • Adaptive receptors: Evolutionarily flexible, adapts to new/mutating pathogens.

Self vs. Nonself

  • Immune cells learn to recognize self and treat everything else as nonself.
  • Self-recognition identifies cells belonging to the body, ensuring safe interactions.
  • Absence of self indicators can trigger an attack, like natural killer cells targeting cells lacking MHC I molecules, such as virally infected or cancerous cells.
  • Nonself recognition uses pattern recognition receptors (PRRs) and somatically generated receptors.

Pattern Recognition Receptors (PRRs)

  • Genetically stable receptors recognize structures produced by microbes or stressed host cells.
  • Structures are encoded directly in the genome and are consistent across individuals of a species.
  • Identify structures associated with microbes but not host cells.
  • Examples include toll-like receptors (membrane-bound) and complement system molecules (soluble).

Somatically Generated Receptors

  • T and B lymphocytes produce these receptors through DNA rearrangement.
  • Each cell generates a unique receptor, resulting in a pool capable of recognizing over 10^10 different structures.
  • Lymphocytes undergo "education" to remove those that could attack normal body structures.
  • Activated lymphocytes launch immune responses to eliminate nonself cells and molecules.

Immunologic Memory

  • Adaptive system can modify responses to subsequent encounters with the same stimulus.
  • Responses can be more rapid and vigorous or depressed, like with harmless substances.
  • Provides the body with the ability to differentiate between threatening and nonthreatening nonself entities.

Microbes

  • Microbes, short for microorganisms, are microscopic organisms that are too small to be seen without aid.
  • Microbes include: bacteria, viruses, fungi, protozoa, algae, and archae.
  • Microbes can be neutral (commensal), pathogen or beneficial (mutualists).

Defense Mechanisms

  • The immune system eliminates threats through isolation, disruption, or ingestion.
  • Mechanisms include mechanical, chemical, and biologic barriers; walling off microbes; disrupting nonself cells via physical damage or apoptosis; phagocytosis; and the action of natural killer cells, antibodies, complement molecules, and T lymphocytes.

Natural Killer (NK) Cells and MHC Class I Molecules

  • Natural killer cells identify abnormal cells by detecting the types and levels of MHC class I molecules on cell surfaces.
  • MHC class I molecules, found on all nucleated host cells, are self-identification markers.
  • NK cells assess MHC I molecule expression after contacting cells expressing stress signals to decide whether to kill them or not.

Pattern Recognition Receptors (PRRs) and PAMPs

  • Pattern recognition receptors (PRRs) bind to pathogen-associated molecular patterns (PAMPs).
  • PRRs recognize molecules widely expressed by microbes but not by host cells.

Somatically Generated Receptors on B and T Lymphocytes

  • B and T lymphocytes somatically generate receptors during development.
  • Somatic receptors are randomly generated and largely vary among individuals.

Influenza Viruses and Immune Recognition

  • Influenza viruses elicit an immune response via pathogen-associated molecular patterns (PAMPs) on their surface.
  • The pattern recognition receptors are found on host cells and molecules, whereas, the pathogen-associated molecular patterns attach to viruses.

Initial Activation of the Immune Response

  • Interactions between pattern recognition receptors and pathogen RNA initiate the immune response, not MHC I molecules, Natural Killers, or the adaptive system..

PAMPs

  • PAMPs are pathogen-associated molecular pattern molecules derived from microorganisms.
  • Recognized by pattern recognition receptor (PRR)-bearing cells of the innate immune system and epithelial cells.

DAMPs

  • Are damage-associated molecular pattern molecules derived from cells.
  • Initiate and perpetuate immunity in response to : trauma, ischemia, and tissue damage.
  • Can occur with or without an infection.

Microbial Defenses against Host Recognition

  • Microbes employ several strategies to evade recognition by the host immune system!

Overwhelming with Tolerance

  • Releasing high doses of antigens into the bloodstream to reduce immunity against them. Releasing overwhelming doses becomes confusing and exhausting leading to decreased immunity.

Molecular Mimicry

  • Antigens look very similar to the hosts own antigens.
  • Immune system struggles with distinguishing the microbe from damaging the host tissue and cells.

Hiding

  • Secreting unique antigens from the host immune system by:
  • Coating themselves with host proteins like fibrin, fibronectin, or even antibodies, so they appear as "self" to the immune system.

Suppressing Host Immune System

  • Weakens immune system.
  • Viruses and protozoa.
  • The host becomes less able to defend against the infection.

Intracellular Evasion

  • Living inside of the hosts cell
  • Prevents antigens from being displayed on the cell surface to prevent an attach.

Antigenic Variation

  • Microbes that alters its antigens that the immune system recognizes, because they are different variations.
  • Forces the host immune system the difficult task of adapting, in order to attack or resolve the pathogen, but this takes time.

Host Defenses: Innate vs. Adaptive Immunity

  • The Host Defenses can fail, which creates a kink in the armour, that leads to infection or possible death.

Innate (Nonspecific) Immune System

  • Provides protection from general invaders.
  • External defense: intact skin, mucous membranes.
  • Cellular attack: complement system.

Adaptive Immune System

  • Provides protection from specific invaders.
  • B and T cells generate antibodies or directly destroy invading cells.

AIDS Patients

  • exhibit low CD4+ cells (T helper cells).
  • Susceptible to bacterial, fungal, and viral infections.

Intravenous Catheter Patients

  • Breach the intact skin barrier.
  • Increased risk for infections with bacteria (Staphylococcus epidermis) or yeast (Candida albicans).

Humoral Immunity

  • B cells and antibodies, tag the invader to prepare the invading microbe for destruction.
  • Targets extracellular pathogens (e.g., bacteria, viruses outside cells, toxins).

Cellular (Cytotoxic) Immunity

  • Targets pathogens inside of cells

Recognizing Cell-Surface Proteins

  • Receptors are utilized to differentiate between host and non-host cells!
  • Pattern recognition receptors (PRRs): Generalized receptors on host cells.
  • B and T cells can produce somatically generated receptors that serve as a specialized key that can unlock a single type of foreign cell surface structure. These receptors are unique to eat and T cell surfaces.

Active Immunity

  • Antibodies are produced.
  • Typically initiated when the body is exposed to live or killed organisms, or toxins.

Passive Immunity

  • Antibodies are PASSED into the body.
  • Mother passes antibodies to baby through breast milk.
  • The greatest distinction between active and passive immunity is that passive immunity implies preformed antibodies, whereas active immunity requires a host pathogen interaction or impactivation.

Active vs. Passive Immunity

  • Active immunity: Long lasting, biological delay for antibody production.

  • Passive immunity: Immediate benefits, short lived protection. The immune protection begins to wane after several days.

    • Could iniate hypersensitivity.

Case study summary

  • 38 year old breastfeeding mother with four children, whom is immunocompromised is receiving IVIG infusions.
  • Is at risk is a possible hypersensitivity, due to the fact that some donor plamas can elicit an immune reaction.

Defining Terms

  • Natural Immunity: Immunity acquired from exposure to the disease through infection.
  • Passive Immunity: Natural immunity provided without the host's own immune system producing antibodies (e.g., infant receiving antibodies from mother).
  • Active Immunity: Host acquires immunity from exposure to the disease and produces antibodies.
  • Acquired Immunity: Immunity received artificially through vaccines or other methods.
  • Acquired and Passive Immunity: Host receives immunity through a vaccine or artificial method, without producing their own immunity (temporary).
  • Acquired and Active Immunity: Host actively produces their own immunity after receiving a killed or weakened form of the disease organism through vaccination (long-lasting immunity).

Innate Immunity

  • The first cellular line of defense.
  • Immediate and identical response after multiple infections

Adaptive Immunity

  • Improves over time, developing specific immunity.
  • Employs diverse antibodies for immunologic memory and long lasting protection

Barriers to Infection: Physical Defenses

  • In addition to microbes and their molecules, other environmental sources (e.g., venoms) can harm tissues.
  • Body's mechanical, chemical, and biologic barriers are the first defense against microbes entering nutrient-rich tissues.
  • They are the moats and walls providing initial protection.

Mechanical Barriers

  • Epidermis and keratinocytes: Provide a watertight barrier and a dry, microbe-inhospitable environment. Continuously dividing keratinocytes and constant sloughing of the superficial epidermal layer removes microbes attached to cutaneous surfaces.

  • Epithelium of mucous membranes: Lines respiratory, gastrointestinal, and urogenital tracts.

  • Cilia: Clear the respiratory tract.

Mucous Membranes

  • Mucous membranes line all body cavities that encounter the enviromnemt like, the repiratory, gastrointestinal, and urogenital tracts.

  • Goblet cells secrete mucus; 4L of mucus are secreted

  • Mucus traps inhaled bacteria, fungi, and particles.

  • Protects epithelial cells from digestive enzymes.

  • Sloughing has a protective effect.

Respiratory Tract

  • Nostril hairs: deposit particles larger than 10 mm in the nasal mucosa.
  • Cilia: move secretions outward for expulsion by coughing and sneezing.
  • Chronic smoking and alcohol consumption can disrupt cilia, increasing infection risk.
  • In cystic fibrosis, defective chloride ion channels lead to thickened mucus, causing recurrent infections

Urinary Tract

  • Urination: inhibits microbe movement into the bladder and kidneys.
  • Catheters increase the risk of urinary tract infections.
  • The acidic secretions of the vagina and microcidal molecules protects the urogenital tract.

Chemical Barriers to Infection

  • Acidic pH: Skin, stomach, and vagina inhibit microbial growth.
  • Microcidal Molecules: α-defensins, β-defensins, cathelicidin, RNases, DNases, and lysozyme provide protective barriers.

pH as a Barrier

  • Pathogens are sensitive to acidity, acid pH inhibits.
  • Skin has about a pH of 5.5.
  • Excessive sebum secretion can affect pH.
  • Stomach acid environment which prevents gut colonization of ingested microbes.
  • The vagina's acidic setting results from lactic acid production by commensal bacteria.

Microcidal Action of Secreted Molecules

  • Tissues in contact with the environment synthesize and secrete molecules to inhibit or kill microbes.
  • Skin is protected by antimicrobial peptides (α-defensins, β-defensins, and cathelicidin), that can damage membrane lysis.
  • Chemoattractants for innate immune system and facilitate ingestion/destruction by phagocytes.
  • Fatty acids released by commensal microbes can also inhibit bacteria.
  • Lysozyme in sweat breaks down peptidoglycan.

Respiratory Tract (Chemicals)

  • Some cells of the respiratory epithelium secrete microcidal molecules such as β-defensins.
  • Help promote engulfment and destruction by phagocytic cells.

Gastrointestinal Tract (Chemicals)

  • The gastrointestinal tact's low pH and epithelial cells produces alpha-defensins and cryptidin, molecules secreted into saliva.
  • Multiple digestive enzymes released that helps break cells.

Lacrimal Secretions

  • Lacrimal glands located above the outer corner of the eye, produce tears.
  • Produce tears and contain lysozyme.

Tears and Lysoszymes

  • Lysozymes in tears prevent cell lysis
  • Tears are made of mucus, water, and oil, and lysozymes.
  • Without a healthy mucus layer, dry spots can form on the cornea.

Mucins: A Selective Protective Barrier

  • Mucins: A structural selective protective barrier for epithelial surfaces that will aid in a variety of functions Alterations in mucin can mean pathological issues, or alterations in normal body function.

Vaginal Candidiasis

  • Antibiotic reduces bacteria, disturbing that areas environment. Lactobacilli helps to balance the vaginal environment and when this is disrupted over production of yeast occurs.

Innate Immune System: An Overview

  • Second line; comes into play when mechanical, chemical, and biological barriers are breached.
  • Quicker response b/c components are always in an activated state.

Distinguishing Self vs. Nonself

  • The system recognizes molecular structures present in infectious microbes but not in the body

Pathogen-Associated Molecular Patterns (PAMPs)

  • Broadly expressed; are sugars, proteins, lipids, nucleic acids, or combinations of the molecules.
  • Recognized cells by pathogen either directly or indirectly.
  • Facilitate ingestion by phagocytes.
  • Can stimulate host cell activating to alter activity-increase secretion of antimicrobial substances.
  • Two common bacteria lipopolysaccharide, peptidoglycan (binded by TLR2 receptors).

Pattern Recognition Receptors

  • Multiple receptors may be engaged during recognition of PaMPs.
  • Receptors mediate internalization, activate the killing of Microbes, and produce chemokines and cytokines

Toll-Like Receptors (TLRs)

  • Mediate Recognition of Diverse pATHOGENS; binding to the cell signals to the Nucleus.
  • That then increases activations genes, cytokines, ect..

Scavenger Receptors

  • Involves; binding of modified low-density lipoproteins, some polysaccharides, and some nucleic acids
  • Involves; internalization of bacteria and phagocytosis of host cells undergoing apoptosis

Opsonins

  • Can be attached to the surface of the microes, makings then more appealing the phagocytes!

Function of Complement

  • Aids or amplifies the immune system.
  • Alerts immune cells, tags invaders, triggers inflammation.
  • Clears immune complexes.
  • Damages pathogens.

Activation of Complement

  • Innate immune system: via the alternative pathway (recognized by a surface) or mannan-binding lectin (MBL) pathway.
  • Adaptive immune system: via the classical pathway (antigen-antibody complexes).
  • Regardless of activation pathway; lysis of bacteria, promotion of phagocytosis triggering inflammation, clearance of immune complexes from circulation.

Alternative Pathway

  • Initiated by the cell-surface traits that are viewed as foregin.
  • Enymes "cleave" C3 into smaller sections.

Terminal or Lytic Pathway

  • Activation starts the MAC creation and lysis of of the cell
  • C5b attatches to bacterial membrane will initial a C6, 7, or C8 adittion

Mannan-Binding Lectin Pathway

  • Activation; Mannan-binding lectin (MBL) binding to carbohydrates in the form of mannose-containing residues of glycoproteins

Anaphylatoxin and Inflammation

  • Trigger release of inflammatory mediators (endothelial cells, phagocytes, and mast cells).
  • Contract smooth muscles.
  • Leakage from capillaries.
  • Can lead to anaphylactic shock (severe).
  • MBL pathway are the molecules that make up anaphylatoxins.
  • Attract and activate leukocytes-help get rid of the pathogens.

Answer: (B) Opsonization.

In the scenario described, the patient's high titers of IgM antibodies specific for Streptococcus pneumoniae capsule indicate an active immune response against the pathogen. IgM antibodies are particularly effective in activating the classical pathway of the complement system.

Pathways to Activation in Complement System

  • Compliment proteins bind stimulate, inflammatory protiens activate, this continues in a cascade manner.
  • Leads to C3 proteins.

Classical Pathway

  • Activated by antigens binding to antibodies.
  • C3 is cleaved into C3a and C3b-sub components.
  • Sub components help create a bridge from the innate and adaptive systems.
C3b
  • Binds to bacterial cell wall tags the intruder for attack.
  • Optimization occurs here when the cell is tagged.
C3a
  • Help recruit inflammatory cells.
  • Ex) mast cells, macrophages, dendritic cells, neutrophils ect..
  • These cells are tagged to help the attacking cell find and mark their target.
    • C3a, recruits anaphylatoxins or other complement peptides that serve to cause smooth muscle contraction, histamine release from mast cells and increased vascular permeability.*
  • Furthermore, an enyzme is created from all of this and is able to lyse c5, releasing a sub component that creates a complex, and the process is repeated again-as needed.
Lectin Pathway

Activated when mannose binding binds carbs and proteins, found on gram negative bacteria. Activates the classical pathway, does not need the help of any antibodies, and the pathway is part of the innate.

Activation requires binding to factor B, and factor D this initiates the cascade! The cascades repeat, depending on variables set in place.

Chemotaxis

  • Chemotaxins create a chemical gradient that immune cells detect through receptors.
  • Neutrophils move toward hight conc of the chemokine or by reorganinzing of the cytoskeleton
  • Neutrophils express receptors for (C5a or II-8) gradient detections, they can migrate through inter cellular pathways that aid in this action!
  • Anaphylatoxins aids as mast cells and baseophils to degranulate as well.
  • Deficiencies of C5, C6, ect.. Can induce a potential issue but individuals with C-9 deficients should be free of such infections.

Phagocytosis

  • An elegant process that culminates in the elimination of invading microorganisms and non self antigens.
  • Engulfment and degradation key word for elimination for phagocytosis.
Flow of steps when eliminating or attacking invading Microbes
  • Phagocytes is a key component here for the glory of phagocytosis.
  • Originating by hemopoietic or stem cells from the bone marrow will differentiate myeloid to phagocytes.
  • The more differences = better

Leukocytes of the Innate Immune System

  • Circulating Leukocytes survey potential sites of micro invasion.
  • Blood cells originate from bone marrow and follow the direction of Myeloid will develop.

Monocytes

  • Comprising -7% of blood volume.
  • Found in circulation one-two days and crossing endothelium by basal dilation.

Macrophages

  • Monocytes travel to tissues differentiated into macrophages.
  • Grow in sized; greater cytoplasmic space.
  • Environment is sampled via phagocytosis.
  • Microbes bound to PRRs or receptors are engulfed by pseudopodia-contained with phagosome-fuses with lysosome.

Presentation

  • Macrophages present digested parts on its surface as digestive parts.
  • Macrophages also secrete chemical signals to enlist cellular support.

Cells of the Innate Immune System

  • Serve as sentinels/defenders against infection.
  • Patrol tissues and organs.
  • Move via lymphatic and blood systems.
  • Specialized roles.
  • Found throughout the body as individual cells or within lymphoid organs and at sites of infection/inflammation.

Leukocytes

  • Broadly classify as granular or agranular.
  • Histologic structure helpful clue to function.

Agranular

  • Lymphocytes (T, B, NK cells) or B cells that enlarge plasma secretors with the help b cells.
  • Monocytes: Phagocytic in circulation- called microphages when tissues are entered.
  • Dendritic Cells: phagocytic Bear treelike cytoplasmic processes .

Granular

  • Neutrophils: have pH.
  • Basophils: have bilobed pH.
  • Eosinophil have bilobed nuclei as well with cytoplasmic granules, use acid pH

Pluripotent Hematopoietic Stem Cells

  • All bloodborne cells derive.
  • Each stem cell has the capacity produce all leukocytes, read blood cells erythroid lineage or platelets thrombocytci lineage.

Derived From

  • Lymphocytes and Plasma Cells: from lymphocytes and plasma cells from stem cells.
  • Myeloid lineage: containing cyto-plasmic are called Eosinophil.
  • Tranport oxygen and carbon oxygen transports (blood, platelets).
  • Most cells from cells with the myeloid lineage or called (lymphocytes plasma) can cause a response from Adaptive repsonse with unit

Lymphocytes as Agranular Leukocyte

  • Differentiate along one of the lymphocytic pathways.

  • B-lymphocytes/B cells live in the bone marrow and synthesize

  • Immunoglobulin.

  • Plasma cells are only cells capable of immunoglobulin synthesis.

  • Natural Killers can rid of cells by killing abnormal activity-malignant Host.

Innate lymphoid
  • Many tissues through the body from skin, lungs, and tissue, quickly infected with signals.
  • Blood with multiple tissues such as Killer Tissue, and the natural killer cells.

Origin of Monocyte Lineage

  • Cells that differentiate from myeloid precursors are called monocytes in circulation.

  • Once they leave circulation and enter tissues, known as macrophages:

  • Actively sample environment by cleaning environment of harmful/ foreign substances.

Basophils

  • Basophils are involved in allergic reactions
  • Are found in tissues
  • Contain cytoplasmic containing vasoactive amines (smooth contraction).
  • Are commonly stained by base loving dies
Eosinophils
  • Contain a loving granules
  • Participations of adaptation from responses when from worn infections that is heliminith
  • Helminth are worm infections!

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The human body is constantly threatened by organisms and molecules. The immune system defends by distinguishing "nonself" threats from "self." Threats originate externally (infectious organisms, toxins) or internally (cancerous changes).

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