Pathogens: Types, Virulence, and Pathogenesis

• Pathogen is an organism causing disease to its host
• Severity of disease symptoms is referred to as virulence

Types of Pathogens

• Viruses, such as Influenza A, shingles, and Hepatitis
• Bacteria, including Lyme disease and Leptospirosis
• Fungi, for example, Candidiasis and Aspergillosis
• Parasitic protozoan diseases like Malaria, Giardia, and Toxoplasmosis
• Prions are pathogens that cause rare progressive neurodegenerative disorders such as Creutzfeldt-Jakob disease (CJD), Alzheimer's, Huntington's, and Parkinson's disease

Primary vs. Opportunistic Pathogens

• A primary pathogen can cause disease in a host regardless of the host's resident microbiota or immune system
• An opportunistic pathogen can only cause disease if the host's defenses are compromised

Pathogenesis

• Pathogenesis is the origination and development of a disease
• Infectious disease results from a competition for supremacy between the parasite and the host
• If the parasite overcomes the host, a change in the general state of good health and disease develops

Host Susceptibility Factors

• Age, especially if very young or very old
• Presence of malnutrition or dehydration
• Underlying chronic disease
• Immobility
• Medications that disrupt or suppress the immune response

How Pathogens Access Hosts

• Pathogen needs to pass through a portal of entry to gain access to a host
• Major portals of entry are the skin, mucous membranes, and parenteral routes

Portal of Entry

• Portal of entry refers to the manner in which a pathogen enters a susceptible host
• The portal of entry must provide access to tissues in which a pathogen can multiply, or a toxin can act
• Three main portals of entry are skin, mucous membranes, and parenteral routes

Mucosal Surfaces

• Mucosal surfaces are the most important portals of entry for microbes
• Include mucous membranes of the respiratory tract, the gastrointestinal tract, and the genitourinary tract
• Some mucosal surfaces are contiguous with the external skin at various body openings
• Pathogen's portal specificity is determined by the organism's environmental adaptions and by the enzymes and toxins they secrete.
• Respiratory and gastrointestinal tracts are particularly vulnerable because particles include microorganisms which are constantly inhaled or ingested, respectively.

Parenteral Route

• Pathogens can enter through a breach in the protective barriers of the skin and mucous membranes
• Pathogens that enter the body this way enter by the parenteral route
• Breaks in the skin (e.g., wounds, insect bites, animal bites, needle pricks) can provide a parenteral portal of entry for microorganisms

Stages of Pathogenesis

• Exposure (contact)
• Adhesion (colonization)
• Invasion
• Infection
• Pathogen must gain entry to the host, travel to the location where it can establish an infection, evade or overcome the host's immune response, and cause damage

Exposure or Contact

• An encounter with a potential pathogen is known as exposure or contact
• Anatomic site through which pathogens can pass into host tissue is called a portal of entry

Adhesion

• Following the initial exposure, the pathogen adheres at the portal of entry
• Adhesion refers to pathogenic microbes' capability to attach to cells
• Molecules (either proteins or carbohydrates) called adhesins are found on the surface of certain pathogens and bind to specific receptors (glycoproteins) on host cells

Biofilm Growth

• Biofilm growth acts as an adhesion factor
• Biofilm is a community of bacteria that produce a glycocalyx, which contributes to the extra polymeric substances (EPS) that allows the biofilm to attach to a surface
• EPS allows the microbe to adhere to the host cells and it harder for the host to physically remove the pathogen
• EPS provides protection against the immune system and antibiotic or antimicrobial treatments
• Some bacteria in a biofilm are in stationary phase, so portions of bacteria in a biofilm are protected against antibiotics

Invasion

• Once adhesion is successful, invasion can proceed
• Invasion involves the dissemination of a pathogen throughout local tissues or the body
• Pathogens may produce exoenzymes or toxins, which serve as virulence factors that allow them to colonize and damage host tissues
• Pathogen's specific virulence factors determine the degree of tissue damage that occurs

Infection

• Following invasion, successful multiplication of the pathogen leads to infection
• Infections can be described as local, focal, or systemic

Local Infection

• Local infection is confined to a small area of the body, typically near the portal of entry

Focal Infection

• In a focal infection, a localized pathogen, or the toxins it produces, can spread to a secondary location

Systemic Infection

• When an infection becomes disseminated throughout the body, this is called a systemic infection

Infection

• Infection, often the first step, occurs when bacteria, viruses or other microbes that cause disease enter your body and begin to multiply
• Disease occurs when the cells in your body are damaged as a result of the infection and signs and symptoms of an illness appear

Virulence

• Virulence is defined as the degree to which a pathogenic organism can cause disease
• Etymologically, the term came from Latin vīrulentus, meaning "full of poison,” “toxin”
• Virulent is a derived word that is used to denote a pathogen as extremely toxic
• The ability of a microorganism to cause damage to its host
• Virulence is the measure of the pathogenicity of an organism
• The degree of virulence is related directly to the ability of the organism to cause disease despite host resistance mechanisms
• Virulence can be measured experimentally by determining the number of bacteria required to cause animal death, illness, or lesions in a defined period after the bacteria are administered by a designated route

Pathogenicity and Virulence

• Virulence is related to pathogenicity in the sense that its meaning is correlated to the manifestation of a disease
• Pathogenicity is defined as the ability of a pathogen to cause disease
• Virulence refers to the degree of pathogenicity of a particular organism
• A virulent pathogen is one that causes damage to its host to an extent that is significantly greater than those caused by a non-pathogenic organism

Virulence Factors

• Virulence factors are molecules or structures that allow microbes to infect hosts, survive, and cause disease
• Factors help pathogens adhere to host cells, invade tissues, evade immune responses, and produce toxins that damage host
• Structural virulence factors help pathogens adhere to host cells, penetrate tissues, evade immune responses, and persist in unfavorable conditions

Capsules

• Bacterial capsules are thick, protective layers made of polysaccharides or polypeptides that help pathogens evade the immune system
• Capsules act as a defense mechanism by preventing phagocytosis, blocking immune recognition, and enhancing bacterial survival inside the host
  • Streptococcus pneumoniae Capsule prevents destruction by immune cells, leading to pneumonia
  • Klebsiella pneumoniae Thick capsule resists phagocytosis, making infections difficult to treat

Pili & Fimbriae

• Pili and fimbriae are hair-like projections that help bacteria stick to host tissues
• Without them, bacteria cannot attach to cells and cause infection
  • Neisseria gonorrhoeae, the bacterium responsible for gonorrhea, uses pili to adhere to cells in the human reproductive tract

Endospores

• Some bacteria form endospores, which are dormant, tough structures that resist heat, drying, and chemicals
• Endospores allow bacteria to survive harsh environments and later reactivate when conditions improve
  • Bacillus anthracis (causes anthrax) forms spores that can survive in soil for years before infecting a new host

Microbial Invasion Enzymes

• Pathogenic bacteria use enzymes to break down barriers in the body, evade the immune system, and spread more effectively

Hyaluronidase

• Hyaluronidase is an enzyme that digests hyaluronic acid, a substance that holds human cells together in connective tissues
  • Streptococcus bacteria use hyaluronidase to penetrate deep into the skin and cause infections like cellulitis

Coagulase

• Coagulase is an enzyme that triggers blood clotting around bacteria, forming a protective barrier
  • Staphylococcus aureus uses coagulase to form abscesses, making infections harder to treat

Immune System Evasion

• Microbes have strategies to avoid being detected or destroyed by the immune system
• Two methods of immune evasion are antigenic variation and intracellular survival

Antigenic Variation

• Some microbes frequently change their outer proteins, making it difficult for the immune system to recognize them
• This allows infections to persist and makes vaccines less effective
  • The flu virus mutates its surface proteins every year, which is why people need a new flu shot annually

Intracellular Survival

• Some bacteria enter and live inside human cells, where immune defenses cannot easily reach them
• They escape immune detection and replicate inside the host before spreading to new cells
  • Salmonella (causes food poisoning) hides inside white blood cells to avoid destruction

Toxin Production

• Toxins are poisonous substances produced by microbes that directly damage host cells

Exotoxins

• Exotoxins are proteins that bacteria actively release into their surroundings
• These toxins target specific cells and organs, leading to severe damage

Neurotoxins

• Neurotoxins are toxins that affect nerve cells (neurons) by disrupting their normal function Ex:
  • Botulinum toxin (Clostridium botulinum)Blocks nerve signals, causing paralysis
  • Tetanus toxin (Clostridium tetani) overstimulates nerve activity, causing uncontrolled muscle contractions (spasms), leading to spastic paralysis

Enterotoxins

• Enterotoxins are bacterial toxins that specifically affect the intestinal tract, leading to symptoms like diarrhea, abdominal cramping, and dehydration Ex:
  • Cholera toxin
  • Staphylococcal enterotoxin (Staphylococcus aureus)

Cytotoxins

• Cytotoxins directly damage or kill cells, leading to tissue destruction Ex:
  • Diphtheria toxin (Corynebacterium diphtheriae
  • Shiga toxin

Endotoxins

• Endotoxins are part of the bacterial cell wall and are only released when the bacteria die
• They trigger massive immune reactions, leading to fever, inflammation, and septic shock

Lipopolysaccharide (LPS)

• Found in the outer membrane of Gram-negative bacteria

Endotoxins vs. Exotoxins

Immunology

• Immunology is the branch of biology that focuses on the immune system, which defends the body against harmful microorganisms (pathogens) such as bacteria, viruses, fungi, and parasites, as well as abnormal cells (like cancer cells)
• Immunology is categorized into eight main branches, each specializing in a specific aspect of immunology

Branches of Immunology

• Immunochemistry examines immune system dysfunctions that cause diseases like autoimmune disorders, allergies, and immunodeficiencies
• Diagnostic Immunology studies the bonding between antigens and antibodies to diagnose immune system disorders
• Clinical Immunology analyzes the molecular mechanisms and components of the immune system, including antigens, antibodies, and immune proteins
• Classical Immunology explores the relationships between pathogens, body systems, and immunity Immuno-oncology focuses on utilizing and enhancing the body's immune system to fight cancer
• Immunomics analyzes the immune system's response and regulation using bioinformatics, genomics, and proteomics
• Immunotoxicology studies how chemicals, toxins, and drugs affect the immune system
• Immunopathology examines immune system reactions to different organisms and conditions in the body

Discoveries in Immunology

• Discovery of Phagocytic Cells Elie Metchnikoff (1880s)
• Discovery of Blood Serum Immunity Emil von Behring & Shibasaburo Kitasato (1890)

Immune System

• A network of cells, tissues, and organs that protect the body from infection, disease, and other harmful substances
• The immune system plays a crucial role in defending the body against microbes, pathogens, and abnormal cells by recognizing and eliminating them

Key Functions of the Immune System

• Defend against microbes; including bacteria, viruses, fungi, and parasites
• Protect against pathogens
• Defend against tumor cell growth
• Eliminate damaged or malignant cells
• Maintain Homeostasis or destruction of abnormal or dead cells

Major Organs of the Immune System

• Thymus
• Peyer's Patches
• Bone Marrow
• Tonsils and Adenoids
• Lymph nodes Spleen
• Appendix

Elements of the Immune System

• Stem cells
• Plasma cell
• Immunoglobulins

Blood Cells of the Immune System

• Red blood cells
• Platelets
• Dendritic cells
• Neutrophils
• B Cells
• T cells

Key Features of T Cells

• T cells (T lymphocytes) are white blood cells that play a crucial role in adaptive immunity
• Unlike B cells, which produce antibodies, T cells directly kill infected cells, activate other immune cells, and regulate immune responses

Types of T cells

• Regulatory T cells suppress or turn off the T cells when an infection is controlled, and they are no longer needed
• Cytotoxic T cells (CD8+ T cells) are a specialized type of T lymphocyte that play a critical role in cell-mediated immunity
• Helper T cells (Th cells) are a crucial subset of T lymphocytes that play a central role in regulating the immune response

Natural Killer Cells (NK cells)

• Named because they easily kill cells infected with viruses

Main Steps for Responding to Invaders

• Innate Recognition (Fast, General Defense)
• Adaptive Recognition (Specific & Long-Term Defense)

Non-Specific Immune Response

• Innate immunity involves barriers that keep harmful materials from entering your body
• These barriers form the first line of defense in the immune response

Key Features of Non-Specific (Innate) Immunity:

• Immediate (acts within minutes to hours)
• Broad-spectrum (works against many pathogens)
• No memory (same response each time)
• Includes physical, chemical, and biological barriers

Examples of Non-Specific Immune Response

• Cough reflex
• Enzymes in tears and skin oils
• Mucus
• Stomach acid
• Skin

Lines of Immune Defense

• First line is Nonspecific defenses
• Second line is When the body is invaded, four important non-specific defenses act: The Inflammatory Response

Aspects of Inflammatory Response

• Increased blood flow increases the blood supply with WBCs, helps to bring white blood cells to the infection site, where they can attack pathogens
• Blood vessels to dilate (vasodilation)
• Increased blood flow
• Capillaries to become more permeable
• Cytokines attract phagocytes

Second Line of Defense: The Temperature Response

• Raises body temperature to create an environment that is less favorable for pathogen survival while enhancing immune cell activity

Second Line of Defense: Proteins

• Immune proteins work together to directly kill pathogens or enhance immune defenses

Second Line of Defense: White Blood Cells

• Important counterattacks in the second line of nonspecific defenses are carried out by three types of white blood cells: Neutrophils, Macrophages and Natural killer cells

Specific Immune Response

• Specific immune responses are triggered by antigens
• Antigens are usually found on the surface of pathogens and are unique to that particular pathogen
• Two components: B Lymphocytes and T Lymphocytes

B Lymphocytes

• B cells secrete antibodies, proteins that bind to antigens
• Humoral Immunity is also called antibody-mediated immunity
• They attack invaders outside the cell

Antigen Presenting Cell (APC)

• B Cells

Memory B Cells

• Some B cells become memory B cells, which "remember" the pathogen and allow for a faster response in future infections

Adaptive Immune Response

• Also known the acquired immune response, as it has to build the immunity up over your lifetime as it encounters new antigens.

Immunity

• Immunity to a disease is achieved through the presence of antibodies that disease in a person's immune system

Types of Immunity

• Active Immunity
• Natural Active Immunity
• Artificial Active Immunity
• Passive Immunity

Types of Passivity Immunity

• Natural Passive Immunity
• Artificial Passive Immunity

Types of Vaccines

• Live-Attenuated Vaccines
• Inactivated Vaccines
• Subunit, Recombinant, Conjugate, Polysaccharide vaccines
• Toxoid Vaccines
• Viral Vector Vaccines

Immunological Disorder

• An immunological disorder is a condition arising from the malfunctioning of the immune system, which is responsible for defending the body against infections and diseases

Types of Immunological Disorders

• hypersensitivity
• Immune Deficiency
• Autoimmune Disorders

Hypersensitivity

• Definition: An exaggerated or inappropriate immune response to antigens, leading to tissue damage

Four Types of Hypersensitivity Reactions

• Type | Immediate (Anaphylactic) Hypersensitivity
• Type II - Cytotoxic Hypersensitivity
• Type III Immune Complex-Mediated Hypersensitivity
• Type IV Delayed-Type (Cell-Mediated)

Immune Deficiency Disorders

• Immune deficiency occurs when one or more components of the immune system are either absent or not functioning properly, leading to increased susceptibility to infections
• Primary Immune Deficiency (PID)
• Secondary Immune Deficiency

Bacteria vs. Other Organisms

• Bacteria have structural virulence factors to help them to attack their targets of opportunity.
• The structure of these bacteria will often determine whether other organisms can cause damage to their own systems.
• Viral and parasitic infections often have the key ability to cause infection and must be treated with antibodies and antivirals.