Viral Infections and Replication

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Questions and Answers

What occurs during lytic infections?

Release of new virus particles causes host cell lysis (correct)

Host cell remains intact

Virus enters a latent state

Host cell undergoes apoptosis

Which type of infection involves viral genetic material remaining in the host cell without immediate replication?

Lytic infections

Latent infections

Persistent infections (correct)

Acute infections

Which antiviral therapy specifically targets the viral DNA polymerase?

Protease inhibitors

DNA polymerase inhibitors (correct)

Reverse transcriptase inhibitors

Neuraminidase inhibitors

What is the mode of action of neuraminidase inhibitors like oseltamivir?

Blocks the neuraminidase enzyme essential for viral release Signup and view all the answers

What can trigger the release of a latent infection from latency?

Stress or environmental changes Signup and view all the answers

Why is the incubation period for viral infections significant?

Viral replication often occurs before symptoms appear Signup and view all the answers

Which aspect of antiviral drugs usually allows them to target only infected cells?

Activation of the drug requires phosphorylation by a viral kinase Signup and view all the answers

Which of the following is an effect of reverse transcriptase inhibitors?

They prevent the formation of viral DNA Signup and view all the answers

What feature distinguishes gram positive bacteria from gram negative bacteria?

Thicker peptidoglycan coat in the cell wall Signup and view all the answers

Which of the following correctly describes the role of lipopolysaccharides in gram negative bacteria?

They form endotoxins when the bacteria dies Signup and view all the answers

Which of the following bacteria is classified as gram negative?

Escherichia Signup and view all the answers

What characteristic of Mycobacteria affects their staining process?

Waxy outer coat Signup and view all the answers

Which of the following is a common genus of gram positive bacteria?

Streptococcus Signup and view all the answers

What is one of the main survival features of bacteria that can form endospores?

Survival in adverse conditions Signup and view all the answers

Which statement is true regarding viral infections?

Latent viral infections remain unaffected by antiviral medications. Signup and view all the answers

What cellular structure is NOT typically found in bacteria?

Nucleus Signup and view all the answers

What is a characteristic of anaerobic bacteria?

They can tolerate low oxygen concentrations. Signup and view all the answers

Which outcome is associated with the release of exotoxins from bacteria?

Stimulation of cell processes that are harmful to the body. Signup and view all the answers

What does LPS primarily stimulate in the body?

Systemic inflammatory response. Signup and view all the answers

Which antibiotics are known to disrupt peptidoglycan synthesis?

Penicillin. Signup and view all the answers

What is a common mechanism of antibiotic resistance in bacteria?

Alteration of antibiotic target sites. Signup and view all the answers

What role do quinolones and sulfonamides play in antibiotic therapy?

They interfere with essential enzyme activity. Signup and view all the answers

Which of the following scenarios best describes the emergence of superbugs?

Bacteria acquiring resistance through genetic mutations. Signup and view all the answers

What is the function of aminoglycosides in bacterial infection treatment?

They disrupt protein synthesis. Signup and view all the answers

Which type of bacteria produces potent paralytic toxins?

Anaerobic bacteria. Signup and view all the answers

What is a significant concern related to acquired antibiotic resistance?

Development of new bacterial strains resistant to treatment. Signup and view all the answers

What is the most common and pathogenic strain of HIV?

HIV1 Signup and view all the answers

Which groups of HIV2 have grown to epidemic proportions?

A and B Signup and view all the answers

Where is HIV2 predominantly seen?

West Africa Signup and view all the answers

Which method is NOT a primary mode of HIV transmission?

Sharing utensils Signup and view all the answers

What does the P24 antigen indicate early in HIV infection?

Presence of HIV Signup and view all the answers

Which cell type does HIV primarily infect?

CD4+ T cells Signup and view all the answers

What process leads to the formation of new viral particles in HIV infection?

Budding Signup and view all the answers

What is a characteristic of AIDS?

CD4+ T cell counts below 200 cells/mm Signup and view all the answers

What is a common opportunistic infection associated with AIDS?

Candidiasis Signup and view all the answers

Which phase of HIV infection can last up to 20 years?

Clinical latency Signup and view all the answers

What consequence occurs due to HIV's effect on CD4+ T cells?

Impairment in the immune response Signup and view all the answers

Which co-infection can increase viral shedding in asymptomatic HIV-infected individuals?

Other sexually transmitted diseases Signup and view all the answers

What is the virus's genetic material form in HIV?

RNA Signup and view all the answers

What is the role of the gp120 protein in HIV infection?

Allows fusion with host cell Signup and view all the answers

What is the primary function of capsids in viruses?

To protect genetic material Signup and view all the answers

How do RNA viruses generate mRNA within host cells?

By synthesizing their own RNA polymerase Signup and view all the answers

Which of the following methods is a common way for viruses to enter host cells?

Penetration via fusion Signup and view all the answers

What role does the Golgi apparatus play in viral infections?

It helps in the assembly of viral components. Signup and view all the answers

Which of the following describes the role of retroviruses in infection?

They integrate their DNA into the host genome. Signup and view all the answers

What is the result of viral lysis on the host cell?

The host cell releases viral particles. Signup and view all the answers

Which type of transmission is responsible for the spread of hepatitis A?

Oral transmission Signup and view all the answers

What initiates the viral replication process inside a host cell?

Recognition and attachment to the host receptor Signup and view all the answers

What is the primary mechanism responsible for type IV hypersensitivity reactions?

Sensitized T-lymphocyte activation Signup and view all the answers

Which condition is classified as an autoimmune disorder?

Systemic lupus erythematosus Signup and view all the answers

In type IV hypersensitivity, what is the typical duration for the manifestation of symptoms after allergen exposure?

Delayed, between 24-72 hours Signup and view all the answers

Which process prevents the immune system from destroying self-antigens?

Immunological tolerance Signup and view all the answers

What occurs during the infiltration of T-lymphocytes in type IV hypersensitivity reactions?

Direct binding to specific target cells and enzyme release Signup and view all the answers

What is the main function of central tolerance in the immune system?

To prevent an immune response to self-antigens and commensal microbes Signup and view all the answers

Which of the following mechanisms is NOT involved in T lymphocyte central tolerance?

Development of memory T cells Signup and view all the answers

What is the purpose of receptor editing in B lymphocyte central tolerance?

To change the specificity of the B lymphocyte's receptors Signup and view all the answers

How does peripheral T lymphocyte tolerance typically manifest?

As anergy or apoptosis upon recognition of self-antigen Signup and view all the answers

What consequence arises from a reduction in CD4 T helper cell populations?

Diminished immune response from B and T lymphocytes Signup and view all the answers

What is a primary function of Treg cells in the context of commensal microbes?

Suppressing the immune response to commensal microbes Signup and view all the answers

Which mechanism leads to B lymphocyte tolerance against self-antigens?

Induction of anergy or apoptosis Signup and view all the answers

What primarily contributes to the development of autoimmune disease?

Genetic factors and environmental triggers Signup and view all the answers

In Systemic Lupus Erythematosus, what is a common clinical consequence?

Vessel injury and inflammation Signup and view all the answers

What can trigger a harmful immune/inflammatory response against commensal microbes?

Self-reactive lymphocytes activation Signup and view all the answers

What role do APCs play in immune responses related to self-antigens?

They present self-antigens to T lymphocytes Signup and view all the answers

What is a potential consequence of infections as environmental triggers for autoimmune diseases?

Stimulating self-reactive B cells Signup and view all the answers

In the context of antigen recognition, which of the following is true about mature B lymphocytes?

They may engage inhibitory receptors upon self-antigen recognition. Signup and view all the answers

What is the primary characteristic of a Type I hypersensitivity reaction?

Production of antigen-specific IgE antibodies Signup and view all the answers

Which of the following is NOT a common allergen associated with Type I hypersensitivity reactions?

Nuclear antigen Signup and view all the answers

What occurs during the initial phase of a Type I hypersensitivity reaction?

Vasodilation and increased capillary permeability Signup and view all the answers

Which immune cells are primarily involved in the late phase of a Type I hypersensitivity reaction?

Eosinophils Signup and view all the answers

What is a clinical consequence of Type I hypersensitivity?

Anaphylaxis Signup and view all the answers

In Type II hypersensitivity reactions, target cells are primarily destroyed by which mechanism?

Complement-mediated lysis Signup and view all the answers

Which of the following describes a mechanism of Type II hypersensitivity involving NK cells?

Antibody-dependent cell-mediated cytotoxicity (ADCC) Signup and view all the answers

Type III hypersensitivity reactions are primarily characterized by the formation of what?

Immune complexes in circulation Signup and view all the answers

What can be a consequence of immune complex deposition in Type III hypersensitivity?

Vasculitis Signup and view all the answers

Which agent is often responsible for the antibody-mediated destruction in Type II hypersensitivity?

Tissue-specific antigens Signup and view all the answers

What happens to eosinophils during a Type I hypersensitivity reaction?

They are recruited by cytokines. Signup and view all the answers

What is the role of Th2 cells in Type I hypersensitivity reactions?

Producing cytokines that stimulate IgE production Signup and view all the answers

Which response best describes the degranulation of mast cells?

Release of histamines and newly formed mediators Signup and view all the answers

Which clinical sign is associated with local responses in Type I hypersensitivity?

Urticaria (hives) Signup and view all the answers

What mechanism is primarily responsible for the deletion of auto-reactive T lymphocytes during central tolerance?

Apoptosis Signup and view all the answers

Which of the following occurs in central B lymphocyte tolerance in response to exposure to self-antigens?

Receptor editing Signup and view all the answers

What effect does a reduction in CD4 T helper cell population have on the immune response?

Weakens B and T lymphocyte response Signup and view all the answers

Which of the following is not a mechanism of peripheral T lymphocyte tolerance?

Increased cytokine production Signup and view all the answers

What is one of the outcomes when immature T lymphocytes encounter self-antigens during central tolerance development?

Apoptosis of auto-reactive T cells Signup and view all the answers

What is the main characteristic of type IV hypersensitivity reactions?

They are delayed hypersensitivity reactions mediated by T-lymphocytes. Signup and view all the answers

What best describes the process of immunological tolerance?

It allows the immune system to recognize self-antigens without mounting a response. Signup and view all the answers

What occurs during the pathophysiology of type IV hypersensitivity skin reactions?

Sensitized T-lymphocytes infiltrate the site and release damaging enzymes. Signup and view all the answers

Which of the following conditions is an example of autoimmunity?

Systemic lupus erythematosus Signup and view all the answers

Which factor primarily triggers the release of immune complexes in Raynaud disease?

Temperature-dependent immune complexes Signup and view all the answers

What is the impact of mature B lymphocytes recognizing self-antigens?

They undergo anergy or apoptosis. Signup and view all the answers

What is the estimated number of bacteria and viruses in the human body?

Approximately $10^{11}$ Signup and view all the answers

Which of the following describes the role of Treg cells in relation to commensal microbes?

They suppress the immune response to prevent inflammation. Signup and view all the answers

What genetic factor is commonly associated with an increased risk of autoimmune diseases?

Inheritance of multiple susceptibility genes, particularly those affecting MHC. Signup and view all the answers

What triggers the activation of self-reactive lymphocytes during infections?

Antigen presenting cells activating through foreign antigen recognition. Signup and view all the answers

Which autoimmune disease is known to affect multiple tissues, including skin and joints?

Systemic lupus erythematosus. Signup and view all the answers

What role do environmental triggers play in the development of autoimmune diseases?

They can stimulate immune responses that may lead to activation of autoreactive lymphocytes. Signup and view all the answers

How does the body typically respond to self-antigens to prevent autoimmune reactions?

Through the process of anergy or apoptosis of reactive lymphocytes. Signup and view all the answers

What characterizes Type I hypersensitivity reactions?

IgE-mediated reactions Signup and view all the answers

Which of the following is a common trigger for Type I hypersensitivity reactions?

Pollens and molds Signup and view all the answers

What is the role of Th2 cells in Type I hypersensitivity reactions?

Helper cells that produce cytokines Signup and view all the answers

Which factor is associated with 'atopy' in individuals?

Higher IgE production Signup and view all the answers

What occurs during the initial phase of a Type I hypersensitivity reaction?

Vasodilation and increased capillary permeability Signup and view all the answers

Which of the following accurately describes the clinical consequence of anaphylaxis?

Systemic bronchospasm and hypotension Signup and view all the answers

What is the common outcome of Type II hypersensitivity reactions?

Destruction of target cells by antibody-mediated mechanisms Signup and view all the answers

Which mechanism results in complement-mediated lysis in Type II hypersensitivity reactions?

Activation of complement proteins Signup and view all the answers

What triggers the formation of immune complexes in Type III hypersensitivity reactions?

Antigen-antibody interactions Signup and view all the answers

Which tissue is commonly affected by immune complex diseases in Type III hypersensitivity reactions?

Kidneys Signup and view all the answers

What distinguishes Type III hypersensitivity from other types?

Involves immune complex formation in circulation Signup and view all the answers

What can result from the degranulation of mast cells in Type I hypersensitivity?

Release of histamine and other mediators Signup and view all the answers

How do natural killer (NK) cells contribute to Type II hypersensitivity reactions?

By releasing toxic molecules to destroy target cells Signup and view all the answers

Study Notes

Viruses and Viral Infections

Viruses are made up of genetic material (DNA or RNA) and a protein capsule (capsid), they may also contain an outer envelope or membrane.
Viruses require a host cell for replication and use the host's cellular machinery for this process.
Viral transmission can occur through routes such as inhaled droplets, oral transmission, direct transfer from other hosts, or bites from vector arthropods.
Once a virus enters a host cell, it recognizes and attaches to cell receptors, penetrates the cell through fusion or endocytosis, and uncoats its genome.
The viral genome then replicates using host enzymes and translates viral structural proteins in the host's endoplasmic reticulum and Golgi apparatus.
Following assembly, the virus is released through budding, exocytosis, or lysis of the host cells.

Viral Replication

Viral replication involves the synthesis of mRNA, which leads to the creation of new viral genomes and protein shells.
DNA viruses make mRNA using the host's DNA polymerase; RNA viruses must produce their own RNA polymerase to form mRNA.
Retroviruses use the viral reverse transcriptase enzyme to convert RNA into DNA, then this DNA is incorporated into the host cell's genome.

Outcomes of Viral Replication

The replication process results in the creation of viral proteins, such as enzymes and regulatory molecules.
Lytic infections lead to the release of new virus particles and the destruction of the host cell.
Persistent infections involve the ongoing presence of the virus, with viral genetic material remaining within the host cell.
Latent infections do not replicate until activated by specific signals.

Principles of Antiviral Therapy

Many viral infections lack effective treatments.
Antiviral drugs target specific steps in viral replication.
DNA polymerase inhibitors, like acyclovir and ganciclovir, block viral DNA polymerase but do not affect cellular DNA polymerase.
Reverse transcriptase inhibitors, like AZT, interfere with viral DNA formation in retroviruses.
Protease inhibitors disrupt protein synthesis needed for HIV replication.
Neuraminidase inhibitors, like oseltamivir, block the activity of the influenza virus neuraminidase enzyme.

Issues in Antiviral Therapy

Viral infections often have long incubation periods, meaning that antiviral treatments may be ineffective once symptoms appear.
Latent viral infections are typically not affected by antiviral medications.
Viruses mutate rapidly, making them prone to developing resistance to antiviral medications.

Bacteria and Bacterial Infections

Bacteria are single-celled organisms with circular DNA and no defined nucleus.
Most bacteria have cell walls, and some contain capsules, flagella, or pili.
Some bacteria can form endospores for survival in harsh conditions.

Bacterial Classification

Gram Staining: This laboratory technique classifies bacteria based on their cell wall structure.
- Gram-positive bacteria: Have a thicker peptidoglycan layer in their cell wall, which stains purple.
- Gram-negative bacteria: Have a thinner peptidoglycan layer and an outer membrane containing lipopolysaccharides (LPS) that stains pink.
Aerobes vs. Anaerobes:
- Aerobic bacteria: Require oxygen for cellular respiration.
- Anaerobic bacteria: Can tolerate low oxygen concentrations and may produce enzymes that break down tissue and toxins.

Outcomes of Bacterial Infection

Exotoxin Release: Exotoxins can inhibit protein synthesis, damage host cells, or disrupt cell function.
Endotoxin Release (LPS): Gram-negative bacteria release LPS, which acts as a pyrogen and stimulates an inflammatory response.

Targets for Antibacterial (Antibiotic) Therapy

Cell Wall: Antibiotic drugs that interfere with peptidoglycan synthesis, like penicillin and cephalosporins, weaken bacterial cell walls.
Cell Membrane: Polymixins, like Polysporin, target LPS and damage the bacterial cell membrane, affecting gram-negative bacteria more strongly.
Bacterial Enzymes: Antibiotics like quinolones, sulfonamides, rifamycins, and lipiarmycins interfere with essential bacterial enzyme activity.
Bacterial Protein Synthesis: Macrolides, lincosamides, and tetracyclines generally inhibit bacterial protein synthesis.

Antibiotic Resistance

Widespread antibiotic use has led to the emergence of bacteria that are resistant to these drugs.
Antibiotic resistance can arise from spontaneous genetic mutations or acquired resistance through transmissible plasmids.
Mechanisms of resistance include altered antibiotic target sites, altered antibiotic uptake, and production of enzymes that inactivate or destroy the antibiotic.
Superbugs are bacterial strains resistant to multiple antibiotics.

Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS)

Strains of HIV

HIV is a retrovirus belonging to the lentivirus genus.
HIV-1 is the most common and pathogenic strain, with multiple subtypes.
HIV-2 is less widespread and found primarily in West Africa.

Epidemiology

Over 39 million people globally are living with HIV, with 1.3 million new cases in 2022.
Most HIV cases occur in eastern and southern Africa, followed by western and central Africa.
In the United States, the majority of new cases are due to male-to-male sexual contact, followed by high-risk heterosexual activity and injected drug use.
Globally, heterosexual transmission is the main mode of HIV spread.

Viral Transmission

HIV is primarily transmitted through blood (IV drug use, blood transfusions) or sexual intercourse.
Vertical transmission (from mother to child) is also possible during pregnancy, delivery, or breastfeeding.
Viral load (amount of virus in the body) is a significant factor in transmission risk.

Pathogenesis

HIV is a retrovirus that uses reverse transcriptase to convert RNA into DNA.
It targets cells with CD4 receptors, including helper T cells, dendritic cells, monocytes, and macrophages.
HIV utilizes a fusion protein (GP41) to fuse with host cells and release its capsid into the cytoplasm.

HIV Infection and Replication Cycle

HIV enters the body and initially infects CD4+ cells.
The viral core enters the cytoplasm and the RNA genome undergoes reverse transcription to produce viral DNA.
This DNA integrates into the host cell's genome, becoming a provirus.
Activation of the host cell can lead to provirus transcription, resulting in the formation of new viral particles.
The virus buds from the host cell, acquiring its outer envelope from the cell membrane.

Mechanisms of Immunodeficiency

HIV replication leads to lysis of infected CD4+ cells.
The bone marrow initially replaces dying CD4+ cells, but over time, these cells become depleted.
Lymphoid tissues are destroyed, impacting the formation of new CD4+ cells.
Uninfected CD4+ cells undergo significant apoptosis, further decreasing their numbers.
These events result in reduced production of cytotoxic T cells and plasma cells, increasing susceptibility to infections.

Disease Progression

Acute Infection (Acute HIV): This phase features mild, flu-like symptoms.
Clinical Latency: This stage is generally asymptomatic, with viral replication continuing at low levels.
AIDS: This stage occurs when CD4+ T cell counts drop below 200 cells/mm3, leading to opportunistic infections, secondary neoplasms, and neurological dysfunction.

Hypersensitivity Reactions

Altered immunologic reaction, resulting in a pathologic response

Type I Hypersensitivity Reaction

IgE-mediated reaction
Characterized by production of antigen-specific IgE after exposure to an antigen
Common allergens: pollens, dusts, molds, food, drugs, bee venom
Genetic predisposition and atopy: mutations affecting IL-4 receptors, levels, IgE, Class II MHC proteins
Atopic individuals tend to produce higher IgE and more IgE receptors on mast cells
They also display increased eosinophil response leading to hyperactive immune responses

Type I Hypersensitivity Reaction - Pathophysiology

Dendritic cells present allergens to Th2 cells
Th2 cells produce IL-4 and IL-5, stimulating IgE-producing B cells
IgE binds to mast cell membrane receptors, activating the mast cell
Degranulation of histamine and release of arachidonic acid metabolites occur
Eosinophils are recruited by Th2 cytokines and mast cell eosinophil chemotactic factor

Type I Hypersensitivity - Phases

Initial phase (5 to 30 minutes): vasodilation, increased capillary permeability, and non-vascular smooth muscle constriction
Late phase (2 to 8 hours): similar responses to the initial phase with intensified granulocyte infiltration (eosinophils, neutrophils) and mucosal damage

Type I Hypersensitivity - Clinical Consequences

Allergic reactions (Local response): itching, urticaria (hives), rhinitis, conjunctivitis
Anaphylaxis (Systemic response): bronchospasm, bronchoconstriction, hypotension, edema, GI cramping

Type II Hypersensitivity Reactions

Destruction of a target cell through antibody action against cell plasma membrane antigens
Common antigens: tissues with HLA or tissue-specific antigens (autoimmune), drugs or drug metabolites bound to cell membranes (often RBCs or platelets), transplanted tissues or organs
Pathophysiology: Mechanisms of Antigen Destruction

Type II Hypersensitivity - Pathophysiology: Mechanisms of Antigen Destruction

Complement-mediated lysis: IgM or IgG reacts with cell surface antigen activating complement, leading to plasma membrane damage and cell injury
Phagocytosis by macrophages: macrophages bind to the Fc portion of antibody on opsonized target cells and phagocytose them
Antibody-dependent cell-mediated cytotoxicity (ADCC): NK cells bind to the Fc portion of antibody and release toxic molecules destroying the target
Inducing target cell malfunction: antibodies binding to target cell receptors alter cell function resulting in changes (example: hyperthyroidism in Graves disease)

Type III Hypersensitivity Reactions

Immune complex diseases
Common antigens: viral, bacterial and parasitic antigens, pollens, vaccines, plasma/serum, nuclear antigens

Type III Hypersensitivity - Pathophysiology

Antigen-antibody complexes form in circulation and deposit on capillary endothelium or extravascular tissues
Complement proteins are activated
Neutrophils ingest the deposited complexes causing tissue damage

Type III Hypersensitivity - Common Target Tissues/Disease Examples

Kidneys: glomerulonephritis
Blood vessels: vasculitis
Arthus reaction: repeated exposure to antigen forms immune complexes in vessel walls causing local inflammatory skin lesions
Raynaud disease: temperature-dependent immune complexes (cryoglobulins) precipitate at below-normal temperatures
Systemic lupus erythematosus: Immune reaction to nuclear antigen

Type IV Hypersensitivity Reactions

Delayed hypersensitivity reaction, mediated by sensitized T-lymphocytes (Tc or Th)
Examples: tissue graft rejection, contact dermatitis, tuberculin reaction, diabetes type 1, rheumatoid arthritis, multiple sclerosis, Crohn disease, toxic shock

Type IV Hypersensitivity Skin Reactions - Pathophysiology

Allergen binds to epidermal cell membrane proteins
T lymphocytes and macrophages infiltrate the site
T lymphocytes bind to target cells and release enzymes (granzymes), damaging or destroying the target cell
Manifestations are delayed for 24-72 hours, and no dermatitis occurs from the primary contact with the allergen

Autoimmunity

Altered immunologic reaction involving B and T lymphocyte response against the body's own cells

Immunological Tolerance

Prevents the immune system from destroying self-antigens
Immunocompetent B and T lymphocytes capable of recognizing all antigens are produced
Mechanisms exist to prevent immune responses to self-antigens and commensal microbes

Generation of Central Tolerance

Immunocompetent (immature) B and T lymphocytes migrate to the bone marrow and thymus
They are exposed to self antigens and develop tolerance
Central T lymphocyte tolerance:
- Immature T lymphocytes migrate to the thymus, encountering self antigens
- Recognition induces apoptosis (negative selection) of CD4 (Th) and CD8 (Tc) lymphocytes or development of regulatory cells (T reg)
Central B lymphocyte tolerance:
- Immature B cells migrate to or stay in the bone marrow, interacting with self antigens
- Recognition induces receptor editing, apoptosis (“deletion”), or anergy (reduced antigen receptor expression)

Generation of Peripheral Tolerance

Central tolerance generation is imperfect
Reduction in CD4 Th cell population minimizes the response

Peripheral T lymphocyte Tolerance

Mature T cells recognizing self-antigens undergo anergy or apoptosis
APCs secrete fewer signaling molecules
Mature T cells are susceptible to the effects of Treg cells

Peripheral B lymphocyte tolerance

Mature B cells recognizing self-antigens undergo anergy or apoptosis
Mature B cells engaging self-antigens activate inhibitory receptors

Generation of Tolerance to Commensal Microbes

Human body harbors ~ 10^14 bacteria and viruses
Abundance of Treg cells secrete interleukins suppressing immune responses to microbes

Development of Autoimmune Disease

Affects 1 out of 5 Americans
Involves inheritance of susceptibility genes and environmental triggers
Susceptibility genes: interfere with self-tolerance pathways, mainly affecting MHC (HLA) genes
Environmental triggers:
- Infections: stimulate APCs activating self-reactive lymphocytes, microbes produce antigens similar to self-antigens
- Sunlight (UV radiation)

Systemic Lupus Erythematosus

Autoimmune disease affecting skin, joints, kidneys, heart, liver, and other tissues
Etiology: Genetic susceptibility and environmental triggers
Pathophysiology:
- Immune complexes deposit in blood vessels, joints, and other tissues
- Complex deposition activates complement and inflammatory cascade
Clinical Consequences: Vessel injury and inflammation
Diagnosis: Based on clinical manifestations, autoantibodies (ANA), and exclusion of other disorders

Hypersensitivity Reactions

An altered immunologic reaction resulting in a pathologic response
4 types of hypersensitivity reactions

Type I Hypersensitivity Reaction

IgE mediated reaction
Characterized by production of antigen-specific IgE after exposure to an antigen
Most responses are to environmental antigens (allergens)
Common allergens:
- Pollens, dusts, molds
- Food
- Drugs
- Bee venom
Genetic Predisposition and Atopy
- Mutations in genes affecting IL-4 receptors, IL-4 levels, IgE receptors, Class II MHC proteins
- Individuals with atopy produce higher amounts of IgE, more IgE receptors on mast cells, and an increased eosinophil response

Type I Hypersensitivity Reaction - Pathophysiology

Dendritic cells present allergens to Th2 cells
Th2 cells produce cytokines (IL-4, IL-5) which stimulate IgE-producing B cells
IgE binds to receptors on the mast cell's plasma membrane, which activates the mast cell
Result is degranulation of histamine from the mast cell and the release of newly formed mediators (arachidonic acid metabolites)
Eosinophils are recruited by cytokines from Th2 cells and eosinophil chemotactic factor from the mast cell

Type I Hypersensitivity Reaction - Clinical Consequences

Two defined phases:
- Initial phase (5-30 minutes): vasodilation, increased capillary permeability, and non-vascular smooth muscle constriction
- Late phase (occurs 2-8 hours): more intense infiltration of tissues with granulocytes (eosinophils, neutrophils), and mucosal damage
Allergic Reactions: itching, urticaria (hives); rhinitis; conjunctivitis
Anaphylaxis:
- Bronchospasm, bronchoconstriction
- Hypotension
- Edema
- GI cramping

Type II Hypersensitivity Reactions

Destruction of target cells due to antibodies against cell surface antigens
Common Antigens:
- Tissues with HLA and/or tissue-specific antigen (autoimmune reactions)
- Drugs or metabolites bound to plasma membrane of cells (often RBCs or platelets)
- Transplanted tissues/organs (including blood transfusions)
Mechanisms of antigen destruction:
- Complement-mediated lysis: IgM/IgG react with cell surface antigens, activating compliment proteins (C5-9) which cause plasma membrane damage and cell injury
- Phagocytosis by macrophages: macrophages recognize and bind to Fc portion of antibody on opsonized target cells and phagocytose the target
- ADCC: NK cells bind to Fc portion of antibody on opsonized target cell and release toxic molecules that destroy the target
- Inducing target cell malfunction: antibody binding to target cell receptors alters normal cellular function

Type III Hypersensitivity Reactions

Immune complex diseases
Common Antigens:
- Viral, bacterial, and parasitic antigens
- Pollens
- Vaccines
- Plasma/Serum
- Nuclear antigens
Pathophysiology:
- Antigen-antibody (immune) complexes form in circulation and deposit on endothelium of capillaries or extravascular tissues
- Compliment proteins are activated
- Neutrophils ingest the deposited antigen-antibody complexes and cause tissue damage
Common Tissues/Disease Examples:
- Kidneys: Glomerulonephritis
- Blood vessels: Vasculitis
- Arthus reaction: repeated local exposure to antigen causes immune complex formation in blood vessel walls leading to local skin lesions
- Raynaud's Disease: Temperature-dependent immune complexes (cryoglobulins) precipitate at below-normal body temperatures
- Systemic Lupus Erythematosus: Immune response to nuclear antigen

Type IV Hypersensitivity Reactions

Delayed hypersensitivity reaction mediated by sensitized T-lymphocytes (Tc or Th)
Examples:
- Tissue graft rejection
- Contact dermatitis
- Tuberculin reaction
- Other diseases: diabetes type 1, RA, MS, Crohn disease, toxic shock
Pathophysiology of Type IV Hypersensitivity skin reactions:
- Allergen binds to proteins on membranes of epidermal cells
- Infiltration of site by T lymphocytes and macrophages
- T lymphocytes bind to target cells and release enzymes (granzymes) that damage/destroy the target cell
Manifestations delayed by 24-72 hours

Autoimmunity

Altered immunologic reaction resulting in B and T lymphocyte response against self-cells

Immunological Tolerance

How the immune system is prevented from destroying self-antigen
Mechanisms prevent the immune system from mounting an immune response to self-antigen (and commensal microbes)

Generation of Central Tolerance

Immunocompetent B and T lymphocytes develop 'tolerance' in bone marrow and thymus by exposure to self-antigens
Central T Lymphocyte Tolerance:
- Immunocompetent T lymphocytes are exposed to self-antigen in the thymus
- Recognition of self-antigen induces:
  - Apoptosis (negative selection) of CD4 (Th) and CD8 (Tc) lymphocytes
  - Development of Regulatory T lymphocytes (Treg)
Central B Lymphocyte Tolerance:
- Immunocompetent B lymphocytes are exposed to self-antigen in the bone marrow
- Recognition of self-antigen induces:
  - Receptor editing
  - Apoptosis
  - Anergy

Generation of Peripheral Tolerance

Central tolerance is imperfect
Peripheral T Lymphocyte Tolerance:
- Mature T lymphocytes recognize self-antigen, causing anergy or apoptosis
- Antigen presenting cells (APCs) secrete fewer signaling molecules
- Mature T lymphocytes are sensitive to the effects of Treg cells
Peripheral B Lymphocyte Tolerance:
- Mature B lymphocytes recognize self-antigen, causing anergy or apoptosis
- Mature B lymphocytes that recognize self-antigen engage inhibitory receptors

Generation of Tolerance to Commensal Microbes

Human body contains ~10^14 bacteria and viruses
Treg cells suppress immune response to commensal microbes

Development of Autoimmune Disease

Immune response against self-antigen affecting approximately 1/5 Americans
Associated with inheritance of susceptibility genes and environmental triggers
Susceptibility Genes: Interfere with self-tolerance pathways, most affecting MHC (HLA) genes
Environmental Triggers:
- Infections: Infections stimulate antigen presenting cells (APCs) that activate self-reactive lymphocytes, and infectious microbes produce antigens similar to self-antigens
- Sunlight (UV radiation)

Systemic Lupus Erythematosus

Autoimmune disease that affects the skin, joints, kidneys, heart, liver, and other tissues
Etiology: Genetic susceptibility with environmental triggers
Pathophysiology: Unclear, but associated with vessel injury and inflammation
Clinical Consequences: Associated with vessel injury and inflammation

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Explore the intricate world of viruses, their structure, and the process of viral replication. This quiz covers key concepts, including how viruses attach, enter host cells, and utilize the host's machinery for their reproduction. Test your understanding of viral transmission and the life cycle of viruses.

Viral Infections and Replication

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Questions and Answers

What occurs during lytic infections?

Which type of infection involves viral genetic material remaining in the host cell without immediate replication?

Which antiviral therapy specifically targets the viral DNA polymerase?

What is the mode of action of neuraminidase inhibitors like oseltamivir?

What can trigger the release of a latent infection from latency?

Why is the incubation period for viral infections significant?

Which aspect of antiviral drugs usually allows them to target only infected cells?

Which of the following is an effect of reverse transcriptase inhibitors?

What feature distinguishes gram positive bacteria from gram negative bacteria?

Which of the following correctly describes the role of lipopolysaccharides in gram negative bacteria?

Which of the following bacteria is classified as gram negative?

What characteristic of Mycobacteria affects their staining process?

Which of the following is a common genus of gram positive bacteria?

What is one of the main survival features of bacteria that can form endospores?

Which statement is true regarding viral infections?

What cellular structure is NOT typically found in bacteria?

What is a characteristic of anaerobic bacteria?

Which outcome is associated with the release of exotoxins from bacteria?

What does LPS primarily stimulate in the body?

Which antibiotics are known to disrupt peptidoglycan synthesis?

What is a common mechanism of antibiotic resistance in bacteria?

What role do quinolones and sulfonamides play in antibiotic therapy?

Which of the following scenarios best describes the emergence of superbugs?

What is the function of aminoglycosides in bacterial infection treatment?

Which type of bacteria produces potent paralytic toxins?

What is a significant concern related to acquired antibiotic resistance?

What is the most common and pathogenic strain of HIV?

Which groups of HIV2 have grown to epidemic proportions?

Where is HIV2 predominantly seen?

Which method is NOT a primary mode of HIV transmission?

What does the P24 antigen indicate early in HIV infection?

Which cell type does HIV primarily infect?

What process leads to the formation of new viral particles in HIV infection?

What is a characteristic of AIDS?

What is a common opportunistic infection associated with AIDS?

Which phase of HIV infection can last up to 20 years?

What consequence occurs due to HIV's effect on CD4+ T cells?

Which co-infection can increase viral shedding in asymptomatic HIV-infected individuals?

What is the virus's genetic material form in HIV?

What is the role of the gp120 protein in HIV infection?

What is the primary function of capsids in viruses?

How do RNA viruses generate mRNA within host cells?

Which of the following methods is a common way for viruses to enter host cells?

What role does the Golgi apparatus play in viral infections?

Which of the following describes the role of retroviruses in infection?

What is the result of viral lysis on the host cell?

Which type of transmission is responsible for the spread of hepatitis A?

What initiates the viral replication process inside a host cell?

What is the primary mechanism responsible for type IV hypersensitivity reactions?

Which condition is classified as an autoimmune disorder?

In type IV hypersensitivity, what is the typical duration for the manifestation of symptoms after allergen exposure?

Which process prevents the immune system from destroying self-antigens?

What occurs during the infiltration of T-lymphocytes in type IV hypersensitivity reactions?

What is the main function of central tolerance in the immune system?

Which of the following mechanisms is NOT involved in T lymphocyte central tolerance?

What is the purpose of receptor editing in B lymphocyte central tolerance?

How does peripheral T lymphocyte tolerance typically manifest?

What consequence arises from a reduction in CD4 T helper cell populations?

What is a primary function of Treg cells in the context of commensal microbes?

Which mechanism leads to B lymphocyte tolerance against self-antigens?

What primarily contributes to the development of autoimmune disease?

In Systemic Lupus Erythematosus, what is a common clinical consequence?

What can trigger a harmful immune/inflammatory response against commensal microbes?

What role do APCs play in immune responses related to self-antigens?

What is a potential consequence of infections as environmental triggers for autoimmune diseases?

In the context of antigen recognition, which of the following is true about mature B lymphocytes?

What is the primary characteristic of a Type I hypersensitivity reaction?

Which of the following is NOT a common allergen associated with Type I hypersensitivity reactions?

What occurs during the initial phase of a Type I hypersensitivity reaction?

Which immune cells are primarily involved in the late phase of a Type I hypersensitivity reaction?

What is a clinical consequence of Type I hypersensitivity?

In Type II hypersensitivity reactions, target cells are primarily destroyed by which mechanism?

Which of the following describes a mechanism of Type II hypersensitivity involving NK cells?

Type III hypersensitivity reactions are primarily characterized by the formation of what?

What can be a consequence of immune complex deposition in Type III hypersensitivity?

Which agent is often responsible for the antibody-mediated destruction in Type II hypersensitivity?