Micro final

Innate vs. Adaptive immunity

Innate Immunity (nonspecific, immediate):

• Speed: Rapid (minutes–hours)

• Specificity: General (recognizes common pathogen patterns via PRRs)

• Memory: None

• Processes:

  • Inflammation

  • Phagocytosis

  • Complement activation

  • Cytokine release

Adaptive Immunity (specific, delayed):

• Speed: Slower (days on first exposure)

• Specificity: Highly specific (antigen-specific receptors)

• Memory: Yes (faster, stronger response upon re-exposure)

• Processes:

  • Antigen presentation (via MHC)

  • Clonal selection & expansion

  • Antibody production

  • Memory cell formation

Types of cells for adaptive vs. innate immunity

Innate:

• Neutrophils – phagocytosis

• Macrophages – phagocytosis + antigen presentation

• Dendritic cells – antigen presentation (bridge to adaptive)

• Natural killer (NK) cells – kill infected/tumor cells

Adaptive:

• B cells → plasma cells (produce antibodies)

• T cells:

  • Helper T cells (CD4⁺) – coordinate immune response

  • Cytotoxic T cells (CD8⁺) – kill infected cells

Major and minor organs of immune system

Major:

• Bone marrow

  • Produces all blood cells (hematopoiesis)

  • B cells mature here

• Thymus

  • T cells mature here

  • Selection process eliminates self-reactive T cells

Minor:

• Lymph nodes

  • Filter lymph

  • Site where B and T cells encounter antigens

• Spleen

  • Filters blood

  • Removes old RBCs and detects blood-borne pathogens

• MALT (Mucosa-Associated Lymphoid Tissue)

  • Includes tonsils, Peyer’s patches, appendix

  • Protects mucosal surfaces (respiratory, digestive, urogenital tracts)

The different classes of white blood cells and cells they arise from

Myeloid Lineage

• Neutrophils – phagocytose bacteria (first responders)

• Eosinophils – defend against parasites, involved in allergies

• Basophils – release histamine, inflammatory responses

• Mast cells – tissue-resident; release histamine (allergy/inflammation)

• Monocytes → Macrophages (in tissues) – phagocytosis + antigen presentation

• Dendritic cells – antigen-presenting cells (activate T cells)

Lymphoid Lineage

• B cells → plasma cells (produce antibodies)

• T cells (mature in thymus):

  • Helper T cells (CD4⁺) – coordinate immune response

  • Cytotoxic T cells (CD8⁺) – kill infected cells

• Natural Killer (NK) cells – kill virus-infected and tumor cells (innate-like)

Antigen presenting cells and what they do

Specialized immune cells that process and display antigens to T cells, linking innate and adaptive immunity.

• Dendritic cells – most important APCs; activate naïve T cells

• Macrophages – phagocytose pathogens + present antigens

• B cells – present antigens to helper T cells

What They Do:

1. Engulf pathogen (phagocytosis or endocytosis)

2. Process antigen into fragments

3. Present antigen on surface using MHC molecules:

   • MHC I → presents to CD8⁺ cytotoxic T cells

   • MHC II → presents to CD4⁺ helper T cells

4. Activate T cells → triggers adaptive immune response

APCs are the “messengers” that show T cells what to attack.

Physical and chemical barriers to infection

Physical Barriers (block pathogen entry):

• Skin – tough, keratinized layer

• Mucous membranes – trap microbes

• Cilia (respiratory tract) – move mucus + pathogens out

• Tears & saliva flow – wash away microbes

Chemical Barriers (destroy/inhibit microbes):

• Lysozyme (in tears, saliva) – breaks down bacterial cell walls

• Stomach acid (HCl) – kills ingested pathogens

• Sebum (skin oils) – acidic, antimicrobial

• Antimicrobial peptides (e.g., defensins) – disrupt microbial membranes

• Low pH (skin, vagina) – inhibits growth

How does phagocytosis work, and what happens to the engulfed pathogen?

A process used by innate immune cells to engulf and destroy pathogens.

Steps of Phagocytosis:

1. Chemotaxis – phagocyte is attracted to infection site by chemical signals

2. Recognition & attachment – pathogen binds to receptors (often helped by opsonins like antibodies or complement)

3. Engulfment – cell membrane surrounds pathogen → forms a phagosome

4. Fusion – phagosome fuses with a lysosome → forms a phagolysosome

5. Digestion – enzymes, acids, and reactive oxygen species break down pathogen

6. Waste removal – debris is expelled from the cell

The engulfed cell is completely broken down and destroyed inside the phagolysosome

Components of the inflammatory process

• Tissue damage or pathogen entry

  • Triggers immune activation

• Resident immune cells (first responders):

  • Macrophages

  • Mast cells

  • Dendritic cells

• Vascular changes (blood vessels):

  • Vasodilation → increased blood flow (redness, heat)

  • Increased permeability → fluid/proteins leave blood (swelling)

• Leukocyte recruitment:

  • Neutrophils and monocytes migrate to site

  • Follow chemical signals (chemotaxis)

  • Exit blood vessels (diapedesis/extravasation)

Key Signaling Molecules of the Inflammatory Process

• Histamine (mast cells)

  • Vasodilation + increased vascular permeability

• Prostaglandins

  • Promote inflammation, pain, fever

• Cytokines (e.g., TNF-α, IL-1, IL-6)

  • Activate immune cells, increase inflammation

• Chemokines

  • Direct movement of immune cells to infection site (chemotaxis)

• Complement proteins

  • Enhance phagocytosis, attract immune cells, lyse pathogens

What happens during vasodilation and extravasation in inflammation?

Vasodilation

• Definition: Widening of blood vessels (especially arterioles)

• What causes it: Histamine, prostaglandins, and other inflammatory mediators

• What happens:

  • Increased blood flow to the infected/injured area

  • More immune cells and plasma proteins arrive at the site

Extravasation (Leukocyte migration out of blood vessels)

• Definition: White blood cells leaving the bloodstream to enter infected tissue

• Steps involved:

  1. Endothelial activation – blood vessel lining expresses adhesion molecules

  2. Rolling & adhesion – WBCs slow down and stick to vessel walls

  3. Diapedesis (transmigration) – WBCs squeeze between endothelial cells

  4. Chemotaxis – WBCs move toward infection site following chemical signals

• Main cells involved: Neutrophils (early), monocytes/macrophages (later)

• Vasodilation = increases blood flow to the area

• Extravasation = immune cells exit blood to reach the infection

How macrophages communicate using cytokinesis

1. Pathogen detection

   • Macrophages recognize microbes using pattern recognition receptors (PRRs)

2. Cytokine release

   • They release cytokines such as TNF-α, IL-1, and IL-6

3. Signal transmission

   • Cytokines bind to receptors on nearby or distant cells

What cytokines do:

• Recruit immune cells (especially neutrophils and monocytes) to infection sites

• Increase inflammation (vasodilation and vascular permeability)

• Activate endothelial cells to help leukocyte extravasation

• Stimulate fever (especially IL-1 and IL-6 acting on the brain)

• Activate other immune cells, including T cells (bridging to adaptive immunity)

What a differential white blood cell count used for

A differential WBC count helps determine what type of immune response is happening based on which white blood cells are elevated or decreased.

To diagnose infection, detect infalmmation or immune response, diagnosing blood and immune disorders

What is the complement cascade and what does it do?

The complement cascade is a protein chain reaction that helps destroy pathogens by tagging them, recruiting immune cells, and directly lysing microbes.

• Complement proteins circulate in an inactive form

• They are activated in a chain reaction (cascade) through:

  • Classical pathway (triggered by antibodies bound to pathogens)

  • Lectin pathway (binds microbial sugars)

  • Alternative pathway (direct activation on pathogen surfaces)

What is an antigen and what is it composed of?

Any substance that is recognized by the immune system as foreign and can trigger an immune response, especially by binding to antibodies or T cell receptors.

What it is composed of:

• Usually proteins (most common and most immunogenic)

• Can also be polysaccharides (carbohydrates)

• Rarely: lipids or nucleic acids, usually when attached to proteins or carriers

What is antigenicity and what factors govern it?

Antigenicity is the ability of a substance (antigen) to bind specifically to immune system products such as antibodies or T-cell receptors and trigger an immune response.

Factors that govern antigenicity:

1. Foreignness (non-self vs self)

   • The more “foreign” a molecule is, the more antigenic it is

   • Immune system usually ignores self-antigens (self-tolerance)

2. Molecular size

   • Larger molecules are generally more antigenic

   • Very small molecules (haptens) are usually not antigenic unless attached to a carrier protein

3. Chemical complexity

   • More complex structures (especially proteins with varied amino acids) are more antigenic

   • Simple or repetitive molecules are less effective

4. Degradability (processing ability)

   • Antigens must be broken down and presented on MHC molecules

   • If a molecule can’t be processed, it may not trigger T cell responses well

5. Exposure/accessibility

   • The more accessible an antigen is (on pathogen surface), the more likely it is to be recognized

How are B cells activated and what happens after they are activated?

B cell activation (two main signals):

1. Antigen binding (Signal 1):

   • A B cell receptor (BCR) binds to a specific antigen

   • The antigen is then internalized and processed

2. Helper T cell help (Signal 2, most important):

   • The B cell presents antigen on MHC II

   • A CD4⁺ helper T cell recognizes it and binds

   • T cell releases cytokines (e.g., IL-4, IL-5, IL-6) to fully activate the B cell

What happens after activation:

1. Clonal selection & expansion

   • The activated B cell rapidly divides into many identical cells

2. Differentiation into:

   • Plasma cells → produce large amounts of antibodies specific to the antigen

   • Memory B cells → long-term immunity, faster response upon re-exposure

3. Antibody functions:

   • Neutralization (block pathogens/toxins)

   • Opsonization (tagging for phagocytosis)

   • Activation of complement system

What are primary and secondary immune responses, and how do IgM and IgG levels change over time?

Primary Immune Response (first exposure to antigen):

• Slower response (days to weeks)

• IgM is produced first

  • First antibody made by activated B cells

  • Appears quickly but is short-lived

• IgG appears later

  • Higher affinity antibodies after class switching

• Lower overall antibody levels

• Memory B cells are formed

Secondary Immune Response (subsequent exposure):

• Faster and stronger response

• Memory B cells activate quickly

• IgG dominates

  • Produced in much higher amounts

  • Faster and more effective response

• IgM still produced, but at lower levels compared to IgG

• Longer-lasting and more efficient immunity

Antibody Pattern Over Time:

• Primary response:

  • Early spike in IgM, then smaller IgG rise

• Secondary response:

  • Rapid, high spike in IgG, minimal IgM change

What do the different types of T cells do?

All T cells originate from bone marrow but mature in the thymus.

1. Helper T cells (CD4⁺)

• Main role: Coordinate and activate other immune cells

• How they work: Release cytokines

• Functions:

  • Activate B cells → antibody production

  • Activate macrophages → enhanced phagocytosis

  • Help activate cytotoxic T cells

• Key idea: “Orchestrators” of immune response

2. Cytotoxic T cells (CD8⁺)

• Main role: Kill infected or abnormal cells

• Targets: Virus-infected cells, tumor cells

• How they kill:

  • Release perforin → creates pores in target cell

  • Release granzymes → trigger apoptosis (cell death)

• Key idea: “Killer cells” of adaptive immunity

3. Regulatory T cells (Tregs)

• Main role: Suppress and control immune response

• Functions:

  • Prevent overactivation of immune system

  • Maintain self-tolerance (prevent autoimmunity)

• Key idea: “Brakes” of the immune system

4. Memory T cells

• Main role: Long-term immune memory

• Functions:

  • Rapid response upon re-exposure to antigen

  • Produce faster, stronger secondary immune response

• Key idea: “Recall system” for future infections

What is an MHC molecule, what does it do, and how do MHC class I and class II differ?

MHC molecules are cell-surface proteins that display antigen fragments to T cells, allowing the immune system to recognize infected or abnormal cells.

• “Show” (present) antigens to T cells

• Enable T cell recognition and activation

MHC Class I:

• Where found: All nucleated cells

• What it presents: Endogenous antigens (from inside the cell)

  • e.g., viral proteins, tumor proteins

• What recognizes it: CD8⁺ cytotoxic T cells

• Outcome: Infected cell is destroyed if recognized

Key idea: “Inside → CD8 → kill”

MHC Class II:

• Where found: Professional antigen-presenting cells (APCs)

  • dendritic cells, macrophages, B cells

• What it presents: Exogenous antigens (from outside the cell)

  • e.g., bacteria that have been engulfed

• What recognizes it: CD4⁺ helper T cells

• Outcome: Activates immune coordination (B cells, macrophages, etc.)

What are microbe-associated molecular patterns (MAMPs)?

MAMPs are “danger signatures” of microbes that alert the innate immune system that an infection is present.

What they are:

• Common, essential components of microbes that are not found in human cells

• Recognized by pattern recognition receptors (PRRs) on immune cells (like macrophages and dendritic cells)

Isotypes, allotypes, and idiotypes

Isotypes

• Differences in the constant region of the heavy chain

• Define the class of antibody

• Same in all members of a species

• Types: IgG, IgA, IgM, IgE, IgD

Function impact: determines what the antibody does

Allotypes

• Genetic variations in antibody genes between individuals of the same species

• Usually in the constant region

• Do NOT change antibody class or basic function much

Idiotypes

• Differences in the variable region (antigen-binding site)

• Each B cell clone has a unique idiotype

• Determines what antigen the antibody binds

What are CD4 and CD8 receptors and what do they do?

CD4 (Helper T cells):

• Binds to MHC class II molecules (on antigen-presenting cells)

• Function:

  • Helps activate and coordinate immune response

  • Stimulates B cells, macrophages, and cytotoxic T cells via cytokines

CD8 (Cytotoxic T cells):

• Binds to MHC class I molecules (on all nucleated cells)

• Function:

  • Identifies infected or abnormal cells

  • Triggers killing of target cells (via perforin and granzymes → apoptosis)

What makes a good vaccine?

A good vaccine is one that safely induces strong, specific, and long-lasting protective immunity without causing disease.

Key features of a good vaccine:

1. Safety

2. Strong immunogenicity

• Effectively activates the immune system

• Stimulates both:

  • Antibody (B cell) response

  • T cell response (cell-mediated immunity)

3. Long-term protection

4. Specificity

• Targets the correct pathogen/antigen without cross-reactivity to host tissues

5. Durability and practicality

• Stable during storage and transport

What are the different basic types of vaccines?

Live attenuated vaccines

• Contain a weakened (but living) form of the pathogen

• Produces strong, long-lasting immunity

Inactivated (killed) vaccines

• Contain killed pathogen

• Usually require boosters

Subunit / recombinant vaccines

• Contain only specific pieces (antigens) of the pathogen

Toxoid vaccines

• Contain inactivated toxins (toxoids) produced by bacteria

• Trains immune system to neutralize toxins

mRNA vaccines

• Contain messenger RNA that codes for a pathogen protein

How vaccines result in long term immunity

Vaccines create long-term immunity by generating memory B and T cells that enable a faster, stronger secondary immune response upon re-exposure to the pathogen.

1. Antigen exposure (via vaccine)

• Vaccine introduces a harmless form of a pathogen (or its antigen)

2. Activation of adaptive immunity

• Antigen-presenting cells (APCs) process the antigen

• Activate helper T cells (CD4⁺)

• Activate B cells and cytotoxic T cells (CD8⁺)

3. Clonal expansion

• Activated B and T cells rapidly divide into identical clones

• Produces large numbers of effector cells

4. Effector response

• B cells → plasma cells → antibodies produced

• T cells → help immune response or kill infected cells

5. Formation of memory cells

• Some B and T cells become memory cells

• These cells persist for years or decades

What is the difference between active and passive immunization, and how are each provided?

Active Immunization

• The body produces its own immune response after exposure to an antigen

• Leads to immunological memory (long-term protection)

• Takes time to develop, but lasts longer

How it is provided:

• Vaccination (most common)

• Natural infection (also causes active immunity, but with disease risk)

Passive Immunization

• The body is given ready-made antibodies

• Provides immediate protection but no memory

How it is provided:

• Maternal antibodies

  • IgG crosses placenta

  • IgA in breast milk

• Antibody injections (immunoglobulin therapy)

  • e.g., rabies immune globulin, antivenom

• Monoclonal antibodies (lab-made antibodies for specific diseases)

Herd immunity 

When a large proportion of a population becomes immune to a contagious disease, making its spread from person to person unlikely and indirectly protecting individuals who are not immune.

How it works:

• If most people are immune (usually through vaccination or prior infection)

• The pathogen has fewer susceptible hosts to infect

• Transmission chains are disrupted

Steps of microbial pathogenesis

Microbial pathogenesis is the process by which a microbe causes disease in a host

1. Exposure (Entry into host)

2. Adhesion (Attachment)

• Microbe attaches to host cells using adhesins (surface proteins, pili, fimbriae)

3. Invasion (Penetration and spread)

• Microbe enters tissues or cells

4. Evasion of immune system

• Avoids detection or destruction

• 5. Damage to host (disease symptoms)

• Caused by:

  • Toxins (exotoxins, endotoxin/LPS)

  • Direct cell destruction

  • Excessive immune response (inflammation)

6. Exit (Transmission to new host)

Methods of microbial attachment

1. Specific receptor binding

• Microbes bind to specific receptors on host cells

• High specificity (lock-and-key interaction)

2. Non-specific forces

• Weak interactions like:

  • Hydrophobic interactions

  • Electrostatic forces

• Help initial contact before firm binding

3. Biofilm formation

• Microbes attach to surfaces and form a protective community (biofilm)

• Increases resistance to immune system and antibiotics

Types of Adhesins

1. Fimbriae (pili)

• Hair-like structures on bacteria

• Bind to specific host cell receptors

2. Surface proteins (adhesins)

• Found on bacterial cell walls or membranes

• Directly bind host receptors

3. Capsular adhesins

• Components of bacterial capsule that help attachment

4. Viral attachment proteins (spikes)

• Viral surface proteins that bind host receptors

Type I and Type IV pili

Type I pili (fimbriae-like adhesins)

• Main function: Adhesion to host cells

• Structure: Short, numerous, rigid hair-like projections

• Key protein: Pilin subunits with adhesins at tips

• Role in infection:

  • Bind to specific receptors on host tissues (e.g., urinary tract cells)

  • Help bacteria resist flushing (e.g., urine flow)

• Movement: No motility function

Type IV pili

• Main functions: Adhesion + motility + DNA exchange

• Structure: Longer, thinner, more flexible than Type I

• Unique feature: Can extend and retract

Roles:

• Twitching motility → pulls bacteria across surfaces

• Attachment to host cells

• DNA uptake (transformation) → horizontal gene transfer

Endotoxins vs exotoxins

Exotoxins

• What they are: Proteins secreted by bacteria

• Source: Mainly Gram-positive and Gram-negative bacteria

• Mode of release: Actively secreted by living bacteria

Key features:

• Highly potent and specific (target specific cells/functions)

• Often heat-labile (easily destroyed by heat)

• Strong immune response → antibodies can neutralize them

• Can be converted into toxoids (used in vaccines)

Endotoxins

• What they are: Part of the outer membrane of Gram-negative bacteria

• Chemical nature: Lipopolysaccharide (LPS, specifically lipid A is toxic)

• Mode of release: Released when bacteria die or divide

Key features

• Less specific but highly inflammatory

• Heat-stable

• Weakly immunogenic (no strong antibody neutralization)

• Triggers strong immune response → fever, shock

Different types of exotoxins and their targets

A-B Toxins (most common type)

Targets:

• Protein synthesis (ribosomes)

• Signaling pathways

Membrane-disrupting toxins

Targets:

• Cell membranes → causes cell lysis

Superantigens

Targets:

• Immune system (T cells)

How do A-B Toxins work?

• Structure:

  • A subunit = active (toxic) part

  • B subunit = binding to host cell receptor

• Mechanism: Enter cell → A subunit disrupts internal function

How does cholera toxin work?

• Binding (B subunit):

  • B subunit binds to GM1 ganglioside receptors on intestinal epithelial cells

• Entry into cell:

  • Toxin is internalized into the cell

• Activation (A subunit):

  • A subunit enters the cytoplasm and permanently activates G proteins (Gs protein)

• Increased cAMP:

  • Activated Gs → stimulates adenylate cyclase

  • → massive increase in cAMP levels

• Ion and water loss:

  • High cAMP causes:

    • Increased Cl⁻ secretion into intestinal lumen

    • Decreased Na⁺ absorption

    • Water follows ions → osmotic water loss

Hemolysins

Hemolysins are a type of exotoxin produced by some bacteria that damage or lyse red blood cells (RBCs) by disrupting their cell membranes.

How they work:

• Bind to host cell membranes (especially RBCs)

• Often form pores (pore-forming toxins) or enzymatically disrupt membrane lipids

• Cause cell lysis → release of hemoglobin

Targets:

• Mainly red blood cells

Types of hemolysis seen in lab culture:

• Alpha (α) hemolysis → partial lysis (greenish discoloration)

• Beta (β) hemolysis → complete lysis (clear zone)

• Gamma (γ) hemolysis → no lysis

Type I, type III, and type IV toxin secretion systems

Bacteria use specialized secretion systems to move toxins or effector proteins into the environment or directly into host cells.

Type I Secretion System (T1SS)

• Mechanism: One-step transport from bacterial cytoplasm → outside cell

• Structure: Protein channel spanning inner + outer membranes

• What it secretes: Toxins and enzymes

Type III Secretion System (T3SS)

• Mechanism: Injects proteins directly into host cells

• Structure: Needle-like “injectisome”

• Function: Acts like a molecular syringe

Type IV Secretion System (T4SS)

• Mechanism: Transfers proteins AND DNA into host cells or other bacteria

• Function: More versatile than T3SS

What is the difference between extracellular, facultative intracellular, and obligate intracellular pathogens?

Extracellular pathogens

• Where they live: Outside host cells (in blood, tissues, or body fluids)

• How they cause disease:

  • Produce toxins

  • Trigger inflammation

  • Avoid phagocytosis (capsules, enzymes)

Facultative intracellular pathogens

• Where they live: Can survive inside or outside host cells

• Strategy:

  • Enter cells to avoid immune system

  • Can also replicate extracellularly

Obligate intracellular pathogens

• Where they live: Must live and replicate inside host cells

• Reason: Lack essential metabolic machinery

Means by which pathogens avoid the host immune system

1. Physical protection

• Capsules (glycocalyx)

  • Prevent phagocytosis (“anti-eating coat”)

• Biofilms

  • Protective community matrix that blocks immune cells and antibiotics

2. Antigenic variation

• Change surface proteins over time

• Prevents immune system from recognizing them again

Intracellular survival

• Hide inside host cells where antibodies cannot reach

Inhibiting phagocytosis

Produce proteins that interfere with immune recognition

Destroying immune molecules

• Produce enzymes that break down antibodies or complement proteins

Immune suppression

• Interfere with cytokine signaling or immune cell activation

Rapid replication or immune overload

• Multiply quickly before immune system can respond effectively

Means by which bacteria evade phagocytic digestion

Prevention of phagocytosis (avoid being engulfed)

• Capsules (glycocalyx)

  • Block recognition and attachment

  • Reduce opsonization (e.g., C3b, antibodies)

• Surface proteins that interfere with binding

Survival inside phagocytes (after engulfment)

• Inhibit phagosome–lysosome fusion

  • Prevent formation of destructive phagolysosome

• Escape from phagosome into cytoplasm

  • Break phagosomal membrane and enter cytosol

Resist killing mechanisms inside phagolysosome

• Neutralize reactive oxygen species (ROS)

  • Produce catalase, superoxide dismutase

• Resist acidic/enzymatic conditions

  • Thick cell walls or stress response proteins

Kill or disable the phagocyte

• Release toxins that damage immune cells

Alter antigen presentation

• Interfere with MHC expression or antigen processing

How HIV attacks T cells

1. Attachment

• HIV binds to CD4 receptors on helper T cells

• Also requires a co-receptor:

  • CCR5 (early infection) or

  • CXCR4 (later stages)

2. Entry

• Viral envelope fuses with T cell membrane

• Viral RNA enters the cell

3. Reverse transcription

• Viral RNA is converted into DNA by reverse transcriptase

4. Integration

• Viral DNA is inserted into host genome using integrase

• Becomes a permanent part of the T cell DNA

5. Replication

• Host cell machinery produces new viral RNA and proteins

• New HIV particles are assembled

6. Release and destruction

• New viruses bud out of the cell

• Host CD4⁺ T cell is damaged or destroyed in the process

Key Idea:

HIV attacks the immune system by infecting CD4⁺ T helper cells, integrating into their DNA, replicating inside them, and ultimately destroying them—leading to immune system collapse over time.

How HPV causes warts

1. Entry through skin breaks

• HPV enters the body through small cuts or abrasions in the skin or mucosa

2. Infection of basal epithelial cells

• Virus infects basal layer keratinocytes (deep skin cells)

• Viral DNA enters host cells

3. Viral replication tied to cell division

• HPV uses host cell machinery to replicate

• Promotes continued division of infected epithelial cells

4. Disruption of cell cycle control

• Viral proteins (especially E6 and E7) interfere with tumor suppressors:

  • E6 → inhibits p53 (prevents apoptosis)

  • E7 → inhibits Rb protein (promotes cell cycle progression)

5. Excess cell growth

• Uncontrolled proliferation of skin cells

• Thickened, raised lesions form

Biofilms and their clinical significance

Biofilms are protective microbial communities that make infections harder to treat by increasing resistance to antibiotics and immune defenses by acting as a protective layer, leading to chronic and device-associated infections.

Common methods for collecting samples from infected areas of the body

Swabs

• Used for surface infections

• Collected from:

  • Skin wounds

  • Throat (throat swab)

  • Nose

  • Genital tract

• Simple and non-invasive

2. Blood samples (blood culture)

• Detects pathogens circulating in the bloodstream

• Collected via venipuncture under sterile conditions

3. Urine samples

• Used for urinary tract infections (UTIs)

4. Sputum samples

• Used for respiratory infections (e.g., pneumonia, TB)

• Deep cough specimen from lungs, not saliva

5. Cerebrospinal fluid (CSF)

• Collected via lumbar puncture

• Used for meningitis or CNS infections

6. Tissue biopsies

• Small pieces of infected tissue removed surgically

• Used for deep or chronic infections

7. Stool samples

• Used for intestinal infections

• Detect bacteria, viruses, or parasites

What a dichotomous key is and how to read one

A dichotomous key is a tool used to identify organisms (or objects) by answering a series of two-choice (either/or) questions based on observable characteristics.

• Start at the first pair of statements

• Choose the option that best matches the organism’s trait

• Follow the direction given after your choice

• Repeat until you reach the final identification

How is selective media used to culture pathogens from nonsterile areas of the body?

Selective media suppresses normal microbiota while allowing pathogens to grow, making it possible to isolate and identify infectious agents from mixed samples.

Methods used to distinguish between Gram negative enteric bacteria

• selective/differential media (like MacConkey agar)

• biochemical tests (IMViC, TSI, urease, oxidase)

• Serological typing

Methods used to distinguish between Gram positive cocci

Gram-positive cocci are identified by a stepwise approach: Gram stain → catalase test → coagulase or hemolysis patterns → additional biochemical tests

Using PCR to identify pathogens

By amplifying and detecting pathogen-specific DNA sequences, allowing rapid and highly sensitive detection of infection even when very few organisms are present.

How immunochromatography assays work and how to interpret them

An immunochromatographic assay (lateral flow test) is a rapid test that detects the presence of a specific antigen or antibody in a sample using antigen–antibody binding on a test strip.

How to interpret results:

• Positive result:

  • Two lines appear (control + test line)

  • Target antigen/antibody is present

• Negative result:

  • Only control line appears

  • No target detected

• Invalid result:

  • No control line appears

  • Test is not reliable and must be repeated

Think of pregnancy tests

Serum antibody assays

tests that detect and measure specific antibodies in a patient’s blood serum, indicating exposure to a pathogen or immune response.

How they work (general principle):

They are based on antigen–antibody binding specificity.

Indirect ELISA (most common format):

1. Antigen coating

• Known pathogen antigen is attached to a test plate

2. Adding patient serum

• If antibodies are present, they bind to the antigen

3. Detection antibody

• A second antibody (linked to an enzyme) binds to patient antibodies

4. Substrate reaction

• Enzyme converts substrate → produces color change

Result interpretation:

• Positive test:

  • Color change occurs → antibodies present in serum

• Negative test:

  • No color change → no antibodies detected

Detects infection history by measuring patient antibodies that bind to known antigens, often using enzyme-based color change reactions like ELISA.

Sensitivity and specificity of tests

Sensitivity

• Measures how well a test correctly identifies people who have the disease

• High sensitivity means:

  • Few false negatives

  • Good for screening tests

Specificity

• Measures how well a test correctly identifies people who do NOT have the disease

• High specificity means:

  • Few false positives

  • Good for confirmatory tests

• Sensitivity = “catch everyone who is sick”

• Specificity = “correctly identify healthy people”

Advantages and disadvantages of rapid point-of-care diagnostic tests

Advantages:

1. Fast results

• Results available in minutes

• Enables immediate clinical decisions

2. Easy to use

• Minimal training required

• Often no specialized lab equipment needed

3. Portable

• Can be used in clinics, emergency settings, or fieldwork

4. Cost-effective

• Generally cheaper than lab-based molecular tests

5. Early treatment and isolation

• Helps quickly identify infectious cases and reduce spread

Disadvantages:

1. Lower sensitivity (in many cases)

• May miss low levels of pathogen (false negatives)

2. Lower specificity (in some tests)

• Possible false positives due to cross-reactivity

3. Limited detail

• Often only shows presence/absence

• Does not quantify pathogen load or provide full identification

4. Quality variation

• Performance can vary between brands or conditions

5. Timing-dependent results

• Accuracy may depend on stage of infection (e.g., early vs late disease)

What is the difference between endemic, outbreak, epidemic, and pandemic?

Endemic

• Disease is constantly present in a population or region

• Occurs at a baseline, predictable level

• Not increasing unusually

Outbreak

• Sudden increase in cases in a small, localized area

Epidemic

• Widespread increase in cases beyond what is normally expected

• Affects a larger region

Pandemic

• An epidemic that spreads across multiple countries or continents

• Global scale of disease spread

Incidence and prevalence

Incidence

• Measures the number of new cases of a disease that develop in a population over a specific period of time

• Focuses only on new infections

• Used to measure risk of developing disease

Prevalence

• Measures the total number of existing cases (new + old) in a population at a given time

• Includes both current and ongoing cases

• Used to measure how widespread a disease is

What are nosocomial infections and how do they spread?

Infections that are acquired in a hospital or healthcare setting and were not present or incubating at the time of admission.

1.Direct contact

• Transfer from healthcare workers, patients, or contaminated hands

• Most common route

• Includes improper hand hygiene

2. Indirect contact (fomites)

• Via contaminated surfaces or medical equipment

3. Droplet transmission

• Spread through respiratory droplets (coughing, sneezing, talking)

4. Airborne transmission

• Small particles remain suspended in air

5. Device-associated infection

• Medical instruments bypass normal barriers

What are index cases and superspreaders?

Index case

• The first identified case of a disease outbreak in a population or group, patient zero

• Used to trace the origin and early spread of an outbreak

Superspreader

• An individual who infects a disproportionately large number of other people compared to the average infected person

What are the links in the chain of infection?

1. Infectious agent (pathogen)

• The microorganism that causes disease

2. Reservoir

• Where the pathogen lives, grows, and multiplies

3. Portal of exit

• Way the pathogen leaves the reservoir

4. Mode of transmission

• How the pathogen spreads to a new host

5. Portal of entry

• Way the pathogen enters a new host

6. Susceptible host

• A person who lacks immunity or has weakened defenses

Stages of surveillance

the systematic process of monitoring and controlling disease spread in a population.

Surveillance follows a cycle: collect data → analyze → interpret → report → act to monitor and control disease spread.

Routine infection control measures

(also called standard precautions) are practices used to prevent the spread of infections in healthcare and community settings

Hand hygiene

• Most important measure

Personal protective equipment (PPE)

• Gloves, gowns, masks, eye protection

Respiratory hygiene

• Covering coughs/sneezes

• Wearing masks when appropriate

Cleaning and disinfection

• Regular disinfection of surfaces and equipment

• Sterilization of medical instruments

Safe injection practices

• Use sterile needles and syringes

Proper waste disposal

Patient isolation (when needed)

How AIDS pandemic has led to rise in reemerging diseases 

Immunosuppression

• HIV-infected individuals have weakened immunity

• Cannot effectively control infections

• Previously controlled pathogens can resurface

2. Increase in opportunistic infections

• Diseases that are normally rare or controlled become common

• 3. Reactivation of latent infections

• Dormant infections (like TB or herpesviruses) become active again

4. Increased transmission

• Immunocompromised individuals may carry higher pathogen loads

• Can spread infections more easily to others

5. Strain on healthcare systems

• Increased disease burden reduces ability to control other infections

• Leads to breakdown in public health measures in some regions

AIDS pandemic contributes to reemerging diseases by weakening immune systems, increasing opportunistic and latent infections, and enhancing transmission of pathogens that were previously controlled