Immune

Question 1

Physical Defenses (Innate Immunity)

Answer 1

• Purpose: Prevent or remove microorganisms from body surfaces

1. Physical Barriers
- Skin: Outer epithelial layer, forms tight barrier to pathogens
- Mucous membranes: Line external body tracts, secrete mucus
- Mucus layer: Sticky complex carbohydrates trap pathogens

2. Mechanical Barriers
- Blinking: Tears contain chemical defenses, flush particles
- Urinating: Flushes microbes from urinary tract
- Sneezing, coughing: Expel mucus and pathogens from airway
- Vomiting: Expels harmful microbes from digestive tract
- Peristalsis, defecation: Continuous involuntary movement removes contents
- Cell shedding: Skin and hair cells slough off microbes
- Mucociliary escalator:
- Found in trachea
- Ciliated epithelial cells push mucus and trapped particles upward
- Note: Smoking chemicals paralyze cilia, ↑ respiratory infection risk

Question 2

Resident Microbiota & Microbiome

Answer 2

Microbiota
- Communities of microorganisms normally associated with a host
- Note: Different parts of the body have different microbiota

Microbial antagonism
- Resident microbiota prevent growth of unwanted microorganisms by:
- Limiting nutrients → resident bacteria already consume them
- Limiting space → occupy surfaces so pathogens can’t adhere
- Creating acidic environments:
- Vaginal microbiota → bacterial products ↓ pH
- Skin microbiota → triglycerides → fatty acids → ↓ pH
- Producing antibacterial compounds:
- Bacteriocins (antimicrobial peptides) → chemicals that kill other bacteria
- Antibiotics → directly inhibit other bacterial growth

Microbiome
- Genetic material of the microbiota

Question 3

Chemicals and enzymes

Answer 3

1. pH
   - Acidic environments inhibit growth of pathogens
   - Found in skin, stomach, vaginal canal
   - Sebum: oil secreted by skin → lubricates, prevents cracking
   
   • Bacteria digest sebum → release fatty acids → ↓ pH (acidic)
2. Salt (salinity)
   - Hypertonic environment → inhibits microbes
   - Found in sweat and tears*
   - Affects enzyme activity and osmotic balance
3. Lactoferrin
   - Glycoprotein secreted by epithelial cells and found in body fluids (saliva, mucus, milk, tears)
   - Binds free iron (Fe³⁺) → sequesters iron needed for bacterial enzyme function
   - ↓ iron availability → inhibits bacterial metabolism and growth
   - Also binds to viral particles → prevents attachment to host cells
4. Lysozyme and lactoperoxidase
   - Lysozyme:
   
   • Secreted in saliva, tears, mucus, and phagocytic cell granules
   • Cleaves β-1,4 glycosidic bonds in peptidoglycan → lyses Gram-positive bacteria
     - Lactoperoxidase:
   • Found in saliva, milk, mucus, and airway secretions
   • Catalyzes reaction: H₂O₂ + SCN⁻ → OSCN⁻ (hypothiocyanite), a reactive antimicrobial compound
   • OSCN⁻ damages bacterial membranes and metabolic enzymes

Question 4

Antimicrobial peptides (AMPs)

Answer 4

• Mode of action:
  
  • Disrupt phospholipid membranes → insert into membrane and form pores → loss of ion gradients → cell lysis -> most common
  • Inhibit intracellular function* → interfere with DNA replication, RNA transcription, and protein synthesis
• Produced by:
  
  • Host epithelial cells (e.g., skin, GI tract, respiratory tract)
  • Resident microbiota (exogenous AMPs)
  • Found in mucus, sweat, and other secretions
• Ancient immunity mechanism
  
  • Found in many animals, plants, fungi
  • Both endogenous and exogenous AMPs contribute to innate defense

Question 5

AMP examples

Answer 5

Question 6

Complement System

Answer 6

• Definition: A set of >25 plasma proteins that function in both innate and adaptive immunity
• General Role: Enhances immune responses by marking pathogens, forming pores in membranes, and recruiting immune cells

Activation Pathways:
1. Classical pathway
- Triggered by antibodies bound to pathogens
- Activates complement cascade
2. Lectin pathway
- Initiated by mannose-binding lectin binding to microbial carbohydrates
- Triggers complement activation
3. Alternate pathway
- Activated spontaneously via hydrolysis of C3

Actions of Complement:
- Opsonization:
- Tags pathogens for enhanced phagocytosis
- Does not initiate phagocytosis but increases efficiency
- Membrane Attack Complex (MAC):
- Forms pores in cell membranes → lysis
- Immune cell activation:
- Complement fragments (e.g. C3a, C5a) stimulate recruitment and activation of neutrophils and monocytes

Question 7

Cytokines

Answer 7

• Definition: Small proteins used for cell-to-cell communication in immune responses
• Secreted by: Many cell types, especially immune cells (e.g. macrophages, dendritic cells, T cells), but also infected or damaged host cells
• Major Types:

1. Interleukins
   
   • Promote differentiation and activation of immune cells, especially B and T lymphocytes
   • Secreted mainly by leukocytes (white blood cells), especially T helper cells
2. Chemokines
   
   • Direct migration of immune cells to infection or injury sites (chemotaxis)
   • Secreted by macrophages, dendritic cells, endothelial cells, and damaged tissue cells
3. Interferons
   
   • Antiviral cytokines:
     
     • Trigger uninfected cells to degrade RNA and inhibit protein synthesis
     • Induce apoptosis in infected cells
     • Activate immune cells (e.g. NK cells, macrophages)
   • Secreted by virus-infected cells, T cells, and NK cells

Question 8

Basophil

Answer 8

• Lineage: Myeloid → Granulocyte

1. Mediate inflammatory response
   → Secrete cytokines, histamine (→ vasodilation), and heparin (→ anticoagulant)
   → Increase capillary permeability to recruit immune cells and proteins
2. Contribute to allergic reactions and anaphylaxis
   → After first exposure to an allergen, B cells produce allergen-specific IgE
   → IgE binds to FcεRI receptors on the surface of basophils - The basophils now “carry” IgE on their surface
   → On re-exposure, the allergen binds to and cross-links these surface-bound IgE antibodies
   → This activates the basophil, triggering release of histamine and inflammatory mediators
   → Results in allergy symptoms like itching, swelling, runny nose, and watery eyes

Question 9

Eosinophil

Answer 9

• Lineage: Myeloid → Granulocyte

1. Defend against parasitic infections (especially worms, protists, fungi)
   → Recruited to sites of infection by cytokines (e.g. IL-5)
   → After first exposure to a parasite or allergen, B cells produce IgE specific to that target
   → Eosinophils upregulate FcεRI (IgE receptors) in response to IL-5 and other signals
   → During re-exposure, eosinophils bind to IgE-coated parasites or allergens via FcεRI
   → This binding activates the eosinophil → triggers degranulation
   → Releases lytic enzymes (e.g. major basic protein) and reactive oxygen species
   → Causes direct damage to parasite membranes and surrounding tissue
2. Contribute to inflammation and allergic responses
   → Secrete pro-inflammatory mediators and cytotoxic granules
   → IgE-mediated activation occurs when eosinophils encounter antigens bound to IgE (not free antigen)
   → Plays a role mainly in the late-phase allergic response
   → Helpful in moderation, but excess activation causes host tissue damage (e.g. in asthma, eczema)
3. Capable of phagocytosis (less than neutrophils)
   → Plays a minor role in clearing smaller pathogens

Question 10

Neutrophil

Answer 10

• Lineage: Myeloid → Granulocyte
• Most abundant circulating leukocyte

1. Inflammation
   
   • Rapidly recruited to sites of inflammation
   • Respond to chemokines (↑ concentration at inflammation sites)
2. Phagocytosis
   
   • Engulf and destroy pathogens
3. Chemical defenses
   
   • Undergo respiratory burst to release:
     
     • Antimicrobial peptides, lysozyme, bleach, and peroxides
4. NETs (Neutrophil Extracellular Traps)
   
   • Release of chromatin, histones, and antimicrobial compounds
   • Immobilizes microbes and enhances immune chemical efficiency
   • Often leads to cell death, though not always (new research)
   • Major component of pus

Question 11

Mast Cell

Answer 11

Mast Cells
- Lineage: Separate from basophils (not from granulocyte lineage)
- Reside in tissues, especially near blood vessels and nerves

1. Inflammation
   
   • Release histamine → vasodilation and ↑ vascular permeability
   • Promote fluid and immune cell movement into tissues
2. Allergic Reactions
   
   • Bind IgE on surface (produced by B cells)
   • Re-exposure to antigen triggers degranulation → release of histamine and cytokines
   • Responsible for seasonal allergies, anaphylaxis, and helminth defense
3. Immune Cell Recruitment
   
   • Release cytokines that attract other immune cells

Question 12

Dendritic Cell

Answer 12

• Lineage: Myeloid → Monocyte lineage
• Bridge innate and adaptive immunity

1. Phagocytosis
   
   • Engulf pathogens into a phagosome
   • Fuse with lysosome → digest pathogen
2. Antigen Presentation
   
   • Display digested antigens on MHC class II molecules
   • Present to helper T cells (CD4⁺) → initiates adaptive immune response
   • Mnemonic: MHC I = “I’m infected”; MHC II = “I’m showing this to you”

• Note: Most important cell for initiating T cell responses

Question 13

Macrophages

Answer 13

• Lineage: Myeloid → Monocyte → Macrophage (mature)
• Found throughout the body; names vary by location

1. Phagocytosis
   
   • Engulf and digest pathogens, debris, and apoptotic cells
2. Antigen presentation
   
   • Display antigens on MHC class II to helper T cells
   • Stimulates adaptive immune activation
3. Initiate inflammation
   
   • Secrete cytokines to recruit and activate other immune cells

• Examples:
  
  • Wandering macrophages (general circulation)
  • Alveolar macrophages (lungs)
  • Microglia (central nervous system)
  • Kupffer cells (liver)

Question 14

Nonspecific Pathogen Recognition (Innate Activation)

Answer 14

This is a key mechanism (but not the only one) by which the innate immune system detects threats. It allows immune cells to rapidly recognize general microbial features without needing prior exposure.

PAMPs (Pathogen-Associated Molecular Patterns)
- Molecular structures unique to pathogens, not present in the host
- Examples:
- Peptidoglycan (bacteria cell walls)
- Flagellin (bacterial flagella)
- Pilin
- Lipopolysaccharide (LPS) (Gram-negative bacteria)

PRRs (Pattern Recognition Receptors)
- Found on innate immune cells (e.g. macrophages, dendritic cells, neutrophils)
- Function: Detect PAMPs → trigger inflammatory and antimicrobial responses
- Activation leads to:
- Cytokine release
- Phagocytosis
- Upregulation of co-stimulatory molecules to alert adaptive immunity

Question 15

Characteristics of Fever

Answer 15

• Definition: Temporary rise in body temperature above normal
• Triggered by: Pyrogens (molecules that signal the hypothalamus to increase set point temperature)

Effects on Host
1. Increases metabolic rate
- Speeds up immune cell responses
- Enhances tissue repair and immune signaling
- Most important function of fever
2. Inhibits microbial activity
- Creates a stressful environment for pathogens
- Slows growth rate but does not kill microbes directly
- Fever does not sterilize via heat—it limits pathogen effectiveness indirectly

Question 16

Acute Inflammation

Answer 16

• Definition: Generalized response to tissue damage or infection involving chemical mediators and cellular defenses

Trigger:
- Histamine and cytokines released by mast cells and basophils initiate the response

Key Events:
1. Vasodilation
- Increases blood flow to damaged tissue
2. Increased capillary permeability
- Allows fluid and immune cells to leave circulation and enter tissue
3. Neutrophil recruitment
- Attracted to site by chemokines
- Primary responder to infection or injury

Note: Inflammation itself is caused by the immune system’s response, not by the pathogen

Question 17

Cardinal signs of inflammation

Answer 17

Question 18

Innate vs adaptive

Answer 18

Question 19

Adaptive (Specific) Immunity

Answer 19

• Specific: Responds to individual antigens (can distinguish strain vs. species)
• Delayed response: Takes several days to activate
• Immunologic memory:
  
  • Remembers previous pathogens
  • Secondary response is faster and stronger

Question 20

Antigens

Answer 20

Structure or molecule that interacts with components of the adaptive immune system

• Antigenicity depends on molecular complexity
  
  • In general, larger and more complex molecules are better antigens
    → Can associate with many different/unique antibodies
    → Activate more unique B and T cells, creating multiple lines of immunologic memory
  • Proteins (high complexity) are better antigens than polysaccharides (lower complexity)

Autoantigens -> Self antigens
- B and T cells are screened during development to ensure they do not recognize or respond to self

Exogenous antigens -> Non-self molecules (anything not from self)
- Examples: flagella, pili, LPS, glycoproteins, capsids, toxins

Question 21

Epitopes

Answer 21

The specific site on an antigen where an antibody binds
- Antigens are small; antibodies cannot bind the entire molecule
- Also called antigenic determinants

• A single antigen may have many different epitopes
• Complex antigens contain multiple unique epitopes
  
  • More epitopes → stronger immune response
  • Each epitope activates unique T and B cells → generates multiple lines of memory cells
• Example:
  
  • A simple molecule (e.g. starch) may have only one epitope
  • A complex protein may have many → higher chance of recognition by an antibody

Question 22

Antibody Structure

Answer 22

• Quaternary protein composed of 4 polypeptide chains:
  
  • 2 heavy chains (larger; defined by mass)
  • 2 light chains
• Variable region:
  
  • Forms the antigen-binding site
  • Compatible with the shape/chemistry of specific epitopes
  • Varies between individual antibodies
  • Formed by both light and heavy chains
  • Created by gene shuffling during B cell development → enables recognition of ~1 quintillion unique epitopes
  • B and T cells are generated randomly (not in response), already primed to recognize millions of epitopes
  • Upon activation, specific antibodies are produced
  • Vaccine non-response may occur if the individual lacks any B or T cell receptor capable of binding the antigen’s epitope
• Constant region:
  
  • Same within each antibody class (e.g. all IgG share one, all IgE another)
  • Recognized by cells of the adaptive immune system (e.g. macrophages, NK cells)
  • Determines the antibody’s class and effector function
  • Located in the Fc region (crystallizable region), distinct from the Fab (binding) region

Question 23

Agglutination

Answer 23

• Definition: Clumping of microbes or particles by antibodies binding to multiple target cells simultaneously
• One antibody can bind identical epitopes on different microbes → forms visible clumps
• Function:
  
  • Immobilizes pathogens, making them easier targets for phagocytosis
  • Enhances clearance and elimination by immune cells
• Especially effective with IgM:
  
  • IgM has 10 binding sites (pentameric structure)
  • Very efficient at cross-linking microbes and forming large immune complexes
• Result: Reduces spread of pathogens and increases immune system efficiency

Question 24

Opsonization

Answer 24

• Definition: The process by which antibodies bind to a pathogen and “tag” it for phagocytosis
  
  • Antibodies coat the pathogen, making it easier for phagocytes to recognize and engulf it
• Mechanism:
  
  • The Fc region of the antibody (constant region) is exposed after binding antigen
  • Phagocytic cells (e.g. macrophages, neutrophils) have Fc receptors that bind the Fc region
  • This interaction signals the immune cell to engulf and destroy the pathogen
• Effect:
  
  • Increases efficiency and speed of phagocytosis
  • Especially important for pathogens that resist direct engulfment
  • Literally makes pathogens easier to “grab” by immune cells
• Clinical note:
  
  • Opsonization enhances clearance of encapsulated bacteria, which are otherwise poorly recognized by innate immunity

Question 25

Neutralization

Answer 25

- *Definition*: Antibodies bind to a **pathogen** or **toxin**, preventing it from interacting with host cells - *Mechanism*: - Antibodies bind to **viral surface proteins** (e.g. glycoproteins) or **bacterial toxins** - This **blocks the binding site** the pathogen or toxin would use to attach to the host cell - Prevents entry of virus or action of toxin - *AB Toxins* (e.g. diphtheria toxin): - Composed of two parts: - **A subunit** (active): causes cellular damage - **B subunit** (binding): binds to host cell receptors - Antibodies neutralize the **B subunit**, preventing toxin attachment and internalization - Only one toxin molecule is involved—so even if **many antibodies** are bound, it is **not agglutination** - *Effect*: - Prevents infection or toxicity without requiring direct destruction of the pathogen - Especially important in neutralizing viruses and secreted bacterial exotoxins