Objectives (2-Awasthi) - Immunity to Infection

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

1. Host

1. Host: Normal immunity and normal physiology (of all systems) are critical.

a. Nonspecific Host Defenses are of vital importance that cannot be over emphasized.

b. Exposure to microorganisms (i.e., normal flora and transient microbes) is normal and to some extent beneficial but is an ultimate source of the problem.

c. Immunopathology—the host response to infection contributes much to disease

d. Host immune response occurs in different phases: Innate immunity, Inflammation, Adaptive immunity, Protective response, Immunological memory

👉 Key role:

• Determines susceptibility, severity, and recovery

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

• Self-study:

  • Describe the changes that may occur in the host and pathogen during a course of infection.

    • HOST

Changes in the Host

👉 Host response evolves through phases:

• Innate → Inflammation → Adaptive → Memory

👉Immunopathology develops

• Host response itself causes tissue damage

👉Host condition may change:

• Improved immunity → recovery

• Immunocompromise → severe/opportunistic infection

👉Outcomes may vary:

• Asymptomatic infection

• Chronic effects (autoimmune, carcinogenic, etc.)

👉 Summary (host changes):

• Immune response activates, escalates, and adapts

• May protect OR cause damage

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

• Self-study:

  • Describe the changes that may occur in the host and pathogen during a course of infection.

    • PATHOGEN

Changes in the Pathogen

• Pathogen must adapt to host environment

  • Different from lab conditions

👉Possible changes:

• Slower growth in vivo

• Intracellular survival

• Persistence in tissues

• Evasion of immune system

👉Interaction with therapy:

• Reduced growth due to drugs

• Increased susceptibility to immune clearance

👉 Summary (pathogen changes):

• Adapts to host conditions

• May become harder to eliminate (e.g., intracellular, slow-growing)

Obj. 1 Summary

Big Picture (High-Yield Concept)

• Infection outcome depends on:

  • Balance between host defenses, pathogen virulence, and therapy

• This balance is:

  • Dynamic and constantly changing during infection

Quick Exam Summary

• Host: immunity, inflammation, immunopathology

• Pathogen: virulence, survival, adaptation

• Drug: shifts balance toward host

• Changes over time:

  • Host → immune phases + possible damage

  • Pathogen → adapts, persists, evades

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

2. Pathogen

2. Pathogen: The basic requirement for pathogenicity of the pathogen is its ability to survive and thrive in the host

a. Few microorganisms can breach the host defenses sufficiently to cause disease.

• Microorganisms, once introduced, do differ in their pathogenicity or virulence; i.e., cell receptors for penetration, mechanisms to resist host defenses, ability to persist in tissues and/or to produce tissue damaging substances.

b. The environment of the pathogen in the host is quite different from that in vitro; i.e., the conditions used for diagnosis and evaluation of anti-infectives.

• Slow microbial growth, avascular lesions, and intracellular infection are some of the factors that may complicate both the host defenses and anti-infective therapy.

👉Pathogens differ in:

• Pathogenicity / virulence

• Ability to:

  • Penetrate (cell receptors)

  • Resist host defenses

  • Persist in tissues

  • Produce tissue-damaging substances

• Important concept:

  • Environment in vivo ≠ in vitro

  • Includes:

    • Slow growth

    • Intracellular infection

    • Avascular lesions

👉 Key role:

• Determines ability to infect, persist, and cause damage

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

2. Drug (Therapy)

3. Therapy: The main function of anti-infectives is to alter the host-pathogen balance of power in the favor of the host.

a. antimicrobial activity is rarely as optimal in vivo as in vitro. Poor drug distribution and rapid metabolism/excretion may complicate therapy along with the factors noted above.

b. Surface damage to a pathogen by anti-infectives may enhance phagocytosis.

c. Early and effective anti-infective therapy may inhibit the immune response (i.e., reduced level and/duration of antigen challenge) which may be good or bad.

👉Important limitations:

• Less effective in vivo than in vitro

• Poor distribution, metabolism, excretion may affect therapy

• Additional effects:

  • Can enhance phagocytosis (surface damage to pathogen)

  • May inhibit immune response if too early/effective

👉Overall concept:

Recovery depends primarily on host defenses, assisted by anti-infectives

👉 Key role:

• Reduces pathogen burden and supports host defenses

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

• Self-study:

  • Write the definition and give examples for the following terms.

    1. Opportunistic pathogens

    2. Innate and Adaptive immunity

    3. Antigen, Epitope and Antibody

Infections caused by microorganisms with low pathogenicity. Immunocompromised individuals are at increased risk.

👉 In simple terms:

• These organisms normally do NOT cause disease in healthy people

• They cause infection when host defenses are weakened

👉Examples:

• Fungi

• Bacteria

• Viruses

👉Quick Exam Line

• Opportunistic pathogens = low pathogenic organisms that cause disease when host defenses are impaired

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

• Self-study:

  • Write the definition and give examples for the following terms.

    1. Opportunistic pathogens

    2. Innate and Adaptive immunity

    3. Antigen, Epitope and Antibody

1. Innate Immunity

Definition:

• Innate immunity is the nonspecific, immediate defense mechanism of the host.

• It is present before exposure to pathogens and does not require prior sensitization.

• From notes:

  • “Nonspecific host defenses are of vital importance”

Key Features

• Rapid (minutes–hours)

• Nonspecific

• No memory

Examples

• Physical barriers: skin, mucous membranes

• Cells: neutrophils, macrophages (phagocytosis)

• Molecules: complement proteins, cytokines

• Processes: inflammation, fever

2. Adaptive Immunity

Definition

• Adaptive immunity is a specific immune response that develops after exposure to an antigen.

• It involves recognition of specific antigens and formation of immunological memory.

• From notes:

  • Occurs as part of host response phases including
    “Adaptive immunity… Protective response… Immunological memory”

Key Features

• Slower initial response (days)

• Highly specific

• Has memory → stronger response upon re-exposure

Examples

• B cells → antibodies (humoral immunity)

  • Example: IgG against bacteria toxins

• T cells → cell-mediated immunity

  • Cytotoxic T cells killing infected cells

• Vaccination → immunological memory

1-Line Exam Answers

• Innate immunity: Immediate, nonspecific host defense present before exposure

• Adaptive immunity: Specific, acquired immune response with memory after antigen exposure

Obj. 1

Describe the triad of infection including the contributions of the pathogen, host, and drug.

• Self-study:

  • Write the definition and give examples for the following terms.

    1. Opportunistic pathogens

    2. Innate and Adaptive immunity

    3. Antigen, Epitope and Antibody

1. Antigen

Definition

• An antigen is a substance that is recognized by the immune system and can induce an immune response.

👉 Key idea:

• It is the “target” of the immune system

Examples

• Bacterial proteins (e.g., surface proteins of Streptococcus)

• Viral proteins (e.g., spike protein of viruses)

• Toxins (e.g., tetanus toxin)

2. Epitope (Antigenic Determinant)

Definition

• An epitope is the specific part of an antigen that is recognized and bound by an antibody or immune receptor.

👉 Key idea:

• It is a small region on the antigen (not the whole antigen)

Examples

• A specific amino acid sequence on a viral protein

• A small region of a bacterial surface antigen

3. Antibody (Immunoglobulin)

Definition

• An antibody is a protein produced by B cells that specifically binds to an antigen (epitope).

👉 Key idea:

• It is the effector molecule that targets antigens

Examples

• IgG → neutralizes toxins and pathogens

• IgM → early immune response

• IgA → mucosal immunity (saliva, tears)

👉High-Yield Relationship (VERY important)

• Antigen = whole structure

• Epitope = specific part of antigen

• Antibody = binds the epitope

👉Quick Exam Line

• Antigen = triggers immune response

• Epitope = specific binding site on antigen

• Antibody = protein that binds the epitope

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Toxigenic Infections

• (1) Exotoxins

• (2) Endotoxins

(1) Exotoxins

Soluble proteins synthesized and secreted by some of the Gram-positive and Gram-negative bacteria.

• Intoxication: Botulism

• Toxigenic Infection: Diphtheria, Tetanus

• Toxin Involvement along with other virulence factors: Scarlet fever, Staphylococcus aureus

-Compared to endotoxin, exotoxins are diverse in their toxicological activity and have potent and specific activity.

(2) Endotoxin (or lipopolysaccharide; LPS)

Cell wall constituent (lipopolysaccharides; LPS) of Gram-negative bacteria. Distinct structure, similar activity.

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Toxigenic Infections

• immune response & pathology

Immune response and pathology

Septic Shock: Lipid A induces release of pro-inflammatory (IL-1beta, TNF-alpha) cytokines

• Septic Shock: Endotoxin or lipopolysaccharide (specifically, lipid A: portion of endotoxin or LPS) induces IL-1 beta and TNF-alpha release from macrophages.

  • These cytokines are intensely inflammatory with actions on granulocytes, the complement and coagulation systems.

  • Bacterial endotoxins are similar in activity regardless of their source but are structurally unique to the organism.

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Toxigenic Infections

• Protective Mechanisms and Management

Protective Mechanisms and Management

• Antibodies

  • IgM bacteriolysins: causes lysis of Gram negative bacteria

  • IgG anti-capsular antibody -may actually be more protective but the capsular polysaccharides are often weakly immunogenic.

  • IgM antibody for lipid A

• Anti-sepsis products:

  • Anti-inflammatory products, Activated protein C

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Extracellular Infection

Most common bacterial infections: Gram + & Gram –

• Other examples: Spirochetes, Mycoplasma

• Most susceptible to current anti-infectives

• Important virulence factor for bacteria: anti-phagocytic capsule

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Extracellular Infection

• Phagocytosis of non-capsulated bacteria and capsulated bacteria

Capsulated bacteria resist phagocytosis.

(See pic for both noncapsulated and capsulated bacteria)

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Extracellular Infection

• Establishment of Extracellular Infection

Phase of Infection

1. Attachment to epithelial receptors:

• Bacterial SIgA proteases

2. Penetration of epithelium (endocytosis):

• Intracellular at this stage

3. Acute inflammatory response:

• Neutrophil, complement, anti-phagocytic factors, local Immune response

4. Lymphatic (&/or hematogenous) spread:

• Systemic Immune response

5. Efferent phase of immune response:

• IgG, IgM; sIgA prevents reinfection

Extracellular Infection = Most susceptible to current anti-infectives

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

1. Extracellular Infection

• Antibodies and neutrophils are important for mucosal host defense.

Antibodies and neutrophils are important for mucosal host defense.

(See pics)

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

• Self-study:

  • Study the examples of extracellular infection, pathologies, and protective host immune mechanisms.

• Toxigenic: toxin-mediated disease → antibodies neutralize toxins

• Extracellular: outside cells → phagocytes + antibodies

• Facultative intracellular: inside/outside → T cells + macrophages

• Obligate intracellular: inside only → cytotoxic T cells

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

3. Facultative Intracellular Infection

Phase of Infection

1. Attachment to epithelial receptors:

• Same as extracellular

2. Penetration of epithelium (endocytosis):

• Same as extracellular

3. Acute inflammatory response

• Resists intracellular killing by neutrophils which die and release organisms

4. Monocyte/Macrophage Involvement:

• May harbor organisms

5. Efferent phase of immune response

• Cell mediated immunity or CMI (e.g., IFN gamma) Macrophage Activation

Facultative Intracellular Infection = Anti-infectives available but therapy generally less effective

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

• Self study:

  • Study the examples of facultative intracellular infection, pathologies, and protective host immune mechanisms.

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

4. Obligate Intracellular Infection

Obligate Intracellular Infection

• Examples: Viruses (including Coronavirus), Chlamydia, and Rickettsia

• Major Virus Interactions: Acute, Chronic, Latent

• Determinants of pathology in virus disease:

  • Tissue tropism of the virus

  • Cytopathology of the virus

  • Immunologically-mediated tissue damage very common

• General Immunologic Principles of Virus Infections

• Interferon (Type I) is major nonspecific defense- NK and T cells contribute

  • CD8+ cytotoxic T cells most important for recovery

  • sIgA and/or serum IgG prevent reinfection

Obj. 2

Differentiate the four main types of infectious disease - toxigenic, extracellular, facultative intracellular, obligate intracellular-including their basic characteristics, common pathogens, and the most important host defenses.

• Self-study

  • Study the examples of obligate intracellular infection, pathologies, and protective host immune mechanisms.

Obj. 3

Distinguish the host defense mechanisms against four main types of infections

A. Eukaryotic Pathogens

• Fungi - Facultative intracellular host-pathogen interaction

B. Bacteria - Extracellular, facultative intracellular host-pathogen interaction

C. Viruses - Obligate intracellular host-pathogen interaction

Self study

• 1. Define following terms in 2-3 sentences: Innate immunity, inflammation, adaptive immunity, protective

  immunity.

Self study

• 2. Discuss the dynamic nature of the triad of infection: how each of the variables—host, pathogen, therapy—can change significantly during any infection?

Self study

• 3. Attempt questions provided behind all the chapters in your textbook

(Look into textbook)

Terms

• Inflammation

Terms

• Innate Immunity

Terms

• Adaptive immunity

Terms

• Antigen presentation

Terms

• Phagocytosis

Terms

• Cell mediated immunity

Terms

• Endotoxin, LPS

Terms

• Intracellular infection

Terms

• Effector immune cells

Terms

• Effector molecules