MICROBIO 1.4

Host-Pathogen Interactions Pt. II

• Host-pathogen interactions are critical in the development and progression of infectious diseases.
• Physicians need to understand these complex interactions to treat and/or prevent diseases at different stages.
• Pathogens can thwart the immune system.
• The immune system fights pathogens, and pathogens can enter the bloodstream.
• Pathogens can cause local infection (step 1), leading to the immune system responding (step 2).
• Spread of bacteria with immune cells throughout the body causes uncontrolled inflammation (step 4).
• This leads to potentially organ damage and death (step 5), if left unmanaged.

Class Objectives

• Differentiate between the 6 stages of establishing and 5 stages (periods) of infectious disease.
• Define and provide examples of virulence factors.
• Deepen the understanding of pathogen transmission.
• Define nutritional needs (e.g., aerobic vs. anaerobic, facultative vs. obligate, and iron need).
• Identify bacterial toxin types and examples.
• Compare and contrast antigenic drift and shift.

Five Stages (Periods) of Infectious Disease

• Incubation: Time from exposure to symptom onset.
• Prodrome: Nonspecific symptoms (e.g., fever, tiredness).
• Specific Disease: Disease-specific symptoms appear.
• Recovery/Convalescence: Symptoms decrease, and the patient recovers.
• Health: May become chronic carriers, or develop a latent infection.

Virulence Factors

• Virulence factors enable pathogens to replicate and spread within the host.
• Different pathogens have various combinations, some shared and some unique, of virulence factors.
• Shared virulence factors include adhesins, capsules that inhibit phagocytosis, and toxins like lipopolysaccharide (LPS).
• Unique virulence factors vary between strains. Examples include botulinum toxin and gp120 in HIV.

Goal: Survival

• Free-living microbes need to colonize surfaces, find a compatible niche, resist immune defenses, and transmit to new hosts.

Nutritionally Compatible Niche

• Microbes select environments based on nutritional needs.
• The human body provides a good niche (sugars, vitamins, minerals, etc.).
• Microbes can be aerobic (need oxygen), anaerobic (without oxygen), or facultative (can adapt).
• Some microbes are obligate, meaning they need a specific environment (a reaction to a particular circumstance).
• Iron is important for some bacteria, and the human body maintains low iron concentrations to prevent bacterial infection; microbes excrete siderophores, iron-chelating agents, that compete to steal iron from host.

Occupancy—Surface Colonization

• Adhesins are cell surface components facilitating bacterial attachment to host cells.
• Some bacteria have surface proteins that bind to host cells (Gram-negative).
• Gram-positive bacteria often have specialized surface proteins (nonfimbrial).
• Capsules inhibit phagocytosis.

Bacterial Colonization

• Bacteria adhere to host cells and extracellular matrix (ECM) components through various mechanisms.

Resistance-Surviving Host Defenses

• Microbes evade the host's initial lines of defense using various strategies, including avoiding complement, subverting phagocytosis, surviving inside phagocytes, becoming intracellular, avoiding immune suppression, diverting lymphocyte function, and using proteolysis.
• Phagocytosis evasion: some microbes avoid phagocytosis.
• Inside phagocytes evasion: some microbes prevent lysosome fusion with phagosomes.
• Escape, resistance to enzymes.

Becoming Intracellular

• Some bacteria thrive within phagocytic cells.
• They can influence host cells to fuse, thus spreading.
• They use the host's cytoskeleton (actin) to move between cells.
• Examples: Listeria monocytogenes (intracellular bacteria).

Immunosuppression

• Immunosuppression damages immune cells like T cells or inhibits cytokine secretion (e.g., HIV).

Diversion of Lymphocyte Function

• Pathogens use superantigens to activate T cells nonspecifically and cause a widespread cytokine release.
• Certain streptococci use this mechanism.

Proteolysis of Antibodies

• Antibodies are cleaved by proteases made by bacteria.
• This prevents antibodies from binding to the pathogen, protecting it.

Latency

• Latency is a resting state of a pathogen in the body without reproducing.
• It's unaffected by the immune system, long-lasting, and may reactivate under stress or decreased immune function.
• Examples: Herpes virus, HIV, and tuberculosis

Antigenic Variation

• Antigenic variation involves changing surface antigens, such as glycoproteins, to evade the host's immune response.
• Examples include Trypanosoma brucei, N. gonorrhoeae, and influenza viruses. This changes the host's antibody's ability to match the cells' different antigens.

Mechanisms that Damage the Host During Infection

• Pathological alterations of metabolism from toxin production or pharmacologic effectors.
• Mechanical damage through blockage of lymphatics or excessive responses from the host.
• Excessive cytokine storm or complement activation by the host itself.
• Host response damage through specific intracellular effects.

Mechanisms for Cell Death

• Lysis
• apoptosis

Bacterial Toxins

• Intracellular toxins.
• Extracellular toxins.
• Exoenzymes.

Test Your Knowledge #1

• The mechanisms microbes use to evade the host's first line of defenses.

Test Your Knowledge #2

• Which mechanism is not a host damaging effect during infection? (and why)

Test Your Knowledge #3

• Identification of suspected bacterial types based on their response to oxygen. Explain the rationale.

Also a Scientist

• Abigail Salyers' career highlights.

This quiz explores the complex dynamics of host-pathogen interactions, focusing on the stages of infectious diseases and the immune response. It covers key topics such as virulence factors, pathogen transmission, and the nutritional needs of pathogens. Understanding these interactions is crucial for effective disease management and treatment.