Immunology Exam 3

What characteristics define mucosal tissue?

• Mucus-secreting epithelium

• Tight junctions

• Directly exposed to external environment

• Major site of pathogen entry

• Produces secretory IgA (SIgA)

What are some examples of mucosal tissue?

• GI tract

• Respiratory tract

• Urogenital tract

• Mammary glands

• Conjunctiva (eye)

What are mucins?

• Large glycoproteins (rich in serine/threonine)

• Form gel-like structure

What is mucus? What role does mucus play in immunity?

• Secretion composed of mucins + enzymes + peptides

• Produced by goblet cells

What are commensal microorganisms?

• Normal microbiota living in symbiosis with host

• Usually beneficial but can become pathogenic if barrier breaks

What role does mucus play in immunity?

• Physical barrier trapping pathogens

• Prevents microbial entry

• Contains antimicrobial substances

What are gnotobiotic mice? How do they differ from mice that contain a regular microbiome?

Mice with known or no microbiota (often germ-free)

What are the anatomical effects? What are the immunological effects? (I don’t expect you to memorize these, but rather understand them and be able to recognize what impact the lack of microbiome might have)

Anatomical effects:

• Underdeveloped gut structures (e.g., smaller Peyer’s patches)

• Thinner mucosal layers

Immunological effects:

• Poor immune system development

• Reduced lymphoid tissue

• Reduced IgA production

• Impaired immune regulation

💡 Takeaway: microbiome is essential for immune development

What are five of the symbiotic benefits of the microbiome?

• Prevent pathogen colonization (competition)

• Aid digestion

• Produce vitamins (e.g., vitamin K)

• Stimulate immune system development

• Maintain epithelial barrier integrity

What are examples of secondary lymphoid tissues at mucosal sites (GALT)?

• Peyer’s patches

• Appendix

• Isolated lymphoid follicles

• Tonsils/adenoids (related)

What is the inductive compartment?

• Site of antigen sampling & lymphocyte activation

• Located under epithelium

• Involves:

  • Dendritic cells

  • M cells

What is the effector compartment?

• Located in lamina propria

• Contains:

  • Plasma cells

  • Effector T cells

  • Macrophages

What are the differences between systemic immunity and mucosal immunity?

Feature	Systemic	Mucosal
Exposure to microbes	Rare	Constant
Inflammation	Strong	Limited
Strategy	Reactive	Proactive
Key regulators	Less Treg	High Treg + IL-10

Mucosal immunity avoids inflammation to prevent damage

How does the innate immune response in the gut work? What role do intestinal epithelial cells play?

• First line defense

• Detect pathogens via PRRs

What is are the types of PRRs on intestinal epithelial cells?

• TLRs (surface)

• NLRs (cytoplasmic)

What are the three responses to PRR activation?

1. NLRP3 inflammasome → NFκB activation

2. Antimicrobial peptides (defensins)

3. Cytokines (IL-1, IL-6)

What is the role of NFκB?

• Master transcription factor

• Drives inflammatory gene expression

Why are innate immune response short-lived?

Epithelial cells replaced every ~2 days

What role/function do intestinal macrophages play?

• Phagocytosis

• Pathogen elimination

How are intestinal macrophages structurally and functionally different than conventional macrophages/blood monocytes?

• ❌ No cytokine secretion

• ❌ No respiratory burst

• ❌ No co-stimulation (not APCs)

• “Inflammation-anergic”

What is the role of NFκB?

Inactivated → prevents inflammation

What is the role of TGFβ

• Suppresses NFκB

• Maintains anti-inflammatory state

What are the cell types of the intestinal epithelium? What are their functions?

Cell	Function
Enterocytes	Absorption
Goblet cells	Mucus
Paneth cells	Antimicrobial peptides
M cells	Antigen transport

What is follicle-associated epithelium and how is it different than other areas of the intestinal epithelium?

• Covers lymphoid follicles

• Lacks goblet + Paneth cells

• More vulnerable → allows antigen entry

What is the role of the microfold (m) cell? What are microfold (m) cells?

• Specialized antigen-sampling cells

• Perform transcytosis (transport antigen across epithelium)

What is transcytosis?

transport antigen across epithelium

What is the intraepithelial pocket?

Contains:

• DCs

• T cells

• B cells

What is oral tolerance?

No immune response to food antigens

How does the experiment with ovalbumin demonstrate the role of oral tolerance?

• Oral exposure → suppressed immune response

• Injection → strong immune response

💡 Shows gut promotes tolerance, not immunity, to food

What is the role of CD103+ DCs? What types of T cells do they present to?

• activate Tregs

Present to:

• Tregs

• TFH cells

When those T cells activate B cells, what antibody isotypes do they produce?

B cell activation → produces:

• IgM → IgA

How do they function in the presence of infection? In the absence?

• No infection: promote tolerance (via IL-10)

• Infection: activate adaptive immunity

Where are mucosal lymphocytes activated?

• Peyer’s patches

• Mesenteric lymph nodes

Once they circulate, where do they go?

Return to mucosal tissues: homing

What are the molecules that allow them to home to the mucosal tissue? (specifically MAdCAM-1)

Key molecules:

• CCR9

• α4β7

• MAdCAM-1

What is the distribution and nature of lymphocytes in the gut?

Always present (even without infection)

Types:

• CD4⁺ (lamina propria)

• CD8⁺ (epithelium)

• αβ and γδ T cells

What are intraepithelial lymphocytes?

• Specialized CD8⁺ T cells

• Functions:

  • Kill infected cells

  • Promote repair

  • Maintain barrier

How do B cells in the gut work? What is the ‘first wave’? What is the ‘second wave’?

First wave:

• IgM secretion

Second wave:

• Class switch → IgA

What is the poly Ig receptor (pIgR)?

• Transports IgA/IgM across epithelium

What is the secretory component?

• Remains attached to IgA

• Protects from degradation

• Anchors to mucus

What is the role of IgA in maintaining tolerance?

• Neutralizes pathogens

• Prevents microbial entry

• Does NOT activate complement → anti-inflammatory

💡 Maintains tolerance while providing protection

What are the differences between IgA1 and IgA2?

Feature	IgA1	IgA2
Hinge	Long	Short
Flexibility	High	Lower
Protease resistance	Low	High

IgA2 dominant in colon (more bacteria)

What are the potential causes of and problems caused by selective IgA deficiency?

Causes:

• Failure to class switch from IgM

Effects:

• Often mild (compensation by other antibodies)

Problems:

• Chronic lung infections

• Giardia infections

Additional:

• Maternal IgA (breastfeeding) provides protection

Know the table titled ‘Distinctive features of the mucosal immune system

• Constant exposure to microbes

• Strong tolerance mechanisms (Tregs, IL-10)

• Minimal inflammation

• Dominance of IgA

• Continuous presence of effector cells

• Specialized antigen sampling (M cells, DCs)

• Shared immunity across mucosal sites

primary immune response

• Driven by naïve B and T cells

• Requires:

  • Antigen presentation

  • Co-stimulation

• Chromatin = closed

• Few transcription factors present

• Higher activation threshold

What are the important cells of immunological memory?

• Long-lived plasma cells (LLPCs) → maintain antibodies

• Memory B cells → rapid antibody production

• Memory T cells → rapid cellular response

What are the important distinctions between long-lived plasma cells and memory B cells?

Feature	LLPCs	Memory B Cells
Location	Bone marrow	Circulate
Division	Do NOT divide	Can proliferate
BCR	❌ None	✅ Present
Function	Constant antibody secretion	Rapid response upon re-exposure
Antibody	Already secreting	Activated upon re-exposure

What role does FcγR2B(1) in the regulation of B cells and B cell memory?

• Expressed on naïve B cells

• Binds IgG → inhibits activation

Key idea:

• Prevents unnecessary activation of naïve B cells

• Memory B cells & plasma cells DO NOT express it
  → allows rapid secondary response

What is hemolytic disease of newborn? (Erythroblastosis Fetalis)

Destruction of fetal RBCs by maternal antibodies

Secondary immune response

• Driven by memory B and T cells

• Faster activation

• No co-stimulation required

• Chromatin = open (epigenetically primed)

• Transcription factors already present

• Lower activation threshold

difference between primary vs secondary immune responses

Primary Response:

• Long lag time (slow activation)

• Lower magnitude

• Shorter duration

• Antibodies: IgM → IgG

• Occurs upon first exposure

Secondary Response:

• Short lag time (rapid response)

• Much greater magnitude

• Longer-lasting

• Dominated by high-affinity IgG (or IgA/IgE)

• Occurs upon repeat exposure

How does hemolytic disease happen?

• Rh⁻ mother exposed to Rh⁺ fetus (first pregnancy)

• Primary response → IgM (does NOT cross placenta)

• Second pregnancy:

  • Memory response → IgG produced

  • IgG crosses placenta → destroys fetal RBCs

What is Rhogam? How does it prevent Erytrhoblastosis Fetalis?

• Injection of anti-RhD IgG antibodies

Mechanism:

• Binds fetal Rh⁺ RBCs in mother

• Prevents maternal immune system from recognizing antigen

• Prevents memory formation

What is the role of CD45 (including CD45RA and CD45RO) in distinguishing between naïve and memory T cells? In this case, how does structure help determine function?

CD45:

• Required for T cell activation

CD45RA (Naïve T cells):

• Larger molecule

• Harder interaction with TCR

• Higher activation threshold

CD45RO (Memory T cells):

• Smaller (alternative splicing)

• Easier TCR interaction

• Lower activation threshold

Structure → Function:

• Smaller CD45RO → closer TCR interaction → faster activation

What are the three types of memory T cells? How do their migration patterns differ from one another?

1. Central Memory (TCM)

• Circulate in:

  • Blood

  • Lymph nodes

• Function: long-term surveillance

2. Effector Memory (TEM)

• Circulate in:

  • Blood + peripheral tissues

• Function: rapid response

3. Resident Memory (TRM)

• Stay in tissues

• Function: immediate local protection

What are the various models of memory cell differentiation (generally, not specifically)? Which is most likely to be correct?

General models:

• Linear differentiation (naïve → effector → memory)

• Parallel differentiation

• Asymmetric division (MOST accepted)

Asymmetric division:

• Unequal distribution of mTORC1

• Results:

  • Proximal → effector cell

  • Distal → memory cell

What is antigenic original sin? Why does it occur? How does it impact the primary immune response to various pathogens?

Immune system prefers existing memory response over new response

Why it occurs:

• Memory cells activate faster than naïve cells

Impact:

• Can lead to less effective response to new pathogens/variants

Why is the flu a good example of original antigenic sin? (high mutation rate)

• High mutation rate

• Old antibodies may not match new strains

What is the importance of cross-reactivity and cross-protection?

Cross-reactivity:

• One immune response recognizes similar antigens

Cross-protection:

• Immunity to one pathogen protects against another

Importance:

• Basis of vaccines

• Provides broader immunity

• Can be beneficial OR sometimes misleading (wrong target)

What is the key difference between active and passive immunization?

• Active immunity = your body makes the response → memory formed

• Passive immunity = receive pre-made antibodies → no memory

active vs. passive; natural vs. acquired?

Type	Natural	Artificial
Active	Infection	Vaccine
Passive	Maternal antibodies	Antibody transfer (e.g., antiserum)

Why might it be advantageous to use passive immunization?

• Immediate protection

• Useful for:

  • Venom/toxins

  • Immunodeficient patients

Why might it be disadvantageous to use passive immunization?

• Temporary

• No memory

• Possible immune reactions

What is the nomenclature used in vaccine (e.g. horse α-snake, etc.)

• Example: horse α-snake antibodies

  • Source (horse) + target (snake toxin)

What are vaccines?

• Preparations containing:

  • Weakened/killed pathogen OR

  • Pathogen components

• Stimulate immune system → memory without disease

Immunization vs vaccination

• Immunization = protection achieved

• Vaccination = exposure event

What is the difference between vaccination and variolation?

• Variolation:

  • Use of live smallpox → risky

• Vaccination:

  • Use of cowpox → safer (cross-protection)

What are the reasons that smallpox is the only disease to be eradicated?

• Low mutation rate

• Strong, effective vaccine

• Human-only reservoir

What are the three major goals of vaccination?

• Safety

• Efficacy (immunogenicity)

• Sustainability (cost, accessibility)

In general, what are correlates of immune protection?

• High IgG levels (systemic)

• High IgA levels (mucosal)

What is meant by rational vaccine design?

Use pathogen structure/genetics to design vaccines

What is meant by reverse vaccinology?

Use knowledge of pathogen biology to identify targets

What characteristics give a vaccine the strongest response?

• Targets immunodominant epitopes

• Activates both B and T cells

Live attenuated

• Weakened live pathogen

Advantages:

• Strong immune response

• Few boosters

Disadvantages:

• Risk of reversion

• Not safe for immunocompromised

• Requires refrigeration

Inactivated or killed

• Dead pathogen

Advantages:

• Safe

• Stable

Disadvantages:

• Weaker response

• Requires boosters

• Poor T cell response

Toxoid

• Inactivated toxin

Example:

• Tetanus

Advantage:

• Neutralizes toxin

Disadvantage:

• Only works for toxin-mediated disease

Purified Protein/Peptide Subunit; Purified Carbohydrate Subunit

Protein:

• Purified proteins

Carbohydrate:

• Polysaccharides

Advantages:

• Safe

• Targeted

Disadvantages:

• Weak immune response

• Carbs → no T cell help (need conjugation)

Recombinant Vectors

• Virus delivers antigen genes

Advantages:

• Strong response

• Mimics infection

Disadvantages:

• Immune response to vector

• Stability issues

mRNA

• mRNA → host makes antigen

Advantages:

• Fast to produce

• Strong immune response

What is the polio virus? What is the disease it causes?

Causes poliomyelitis (paralysis)

What are the two types of polio vaccines? What are the similarities between the two? What are the differences?

Feature	Salk	Sabin
Type	Killed	Live attenuated
Route	Injection	Oral
Risk	Safer	Risk of reversion

What are the types of vaccine excipients? What are their purposes?

• Preservatives → prevent contamination

• Adjuvants → boost immune response

• Stabilizers → storage stability

• Antibiotics → prevent bacterial growth

• Inactivating agents → kill pathogens

What is an adjuvant?

• Enhance immune response

Functions:

• Increase inflammation

• Improve antigen presentation

• Stabilize antigen

What are liposomes? What are ISCOMs?

• Delivery systems

• Help antigens enter cells → activate CTL response

What is a vaccine schedule? What is a booster?

• Schedule = timing of doses

• Booster = additional dose to strengthen immunity

What is the NVICP? Why was it established? How does it work?

• Compensation system for vaccine injury

Why:

• Created after vaccine safety concerns

How:

• No-fault system

• Requires “preponderance of evidence”

• Panel includes medical, legal, and lay experts

What is VAERS? How does it work?

• Reporting system for adverse events

• Monitors vaccine safety

What are the consequences of non-vaccination?

• Disease outbreaks

• Loss of herd immunity

• Increased mortality

What are therapeutic vaccines? What are some examples?

• Treat disease (not prevent)

Examples:

• Cancer vaccines

Can you distinguish between the terms coronavirus, SARS-CoV-2, and COVID19?

• Coronavirus = virus family

• SARS-CoV-2 = specific virus

• COVID-19 = disease

What is the spike (S) protein

• Viral surface protein

• Binds to ACE2 receptor

How does coronavirus infect us?

• Inhalation of droplets

• Spike protein binds ACE2

• Virus enters cell

• Replicates

• Spreads → inflammation

What is the ACE2?

• Host receptor on respiratory cells

• Entry point for virus

What is herd immunity? How is it defined? How is it determined?

• When enough people are immune → spread decreases

Determined by:

• R₀ (infectivity)

Regarding infectious disease, what is the relationship between infectivity and mortality (in general)? What is the relationship between infectivity and mode of transmission (in general)?

• Higher infectivity → usually lower mortality

• Higher mortality → usually lower spread

Mode of transmission:

• Airborne → higher spread

• Contact → lower spread

How do mRNA vaccines work?

• mRNA enters host cells

• Cells produce antigen (spike protein)

• Immune system responds

• Memory formed

what is hypersensitivity?

• An exaggerated or inappropriate immune response

• Causes more damage than the antigen/pathogen itself

• Typically occurs during secondary immune responses

Which characteristics make parasites different than other parasites?

• Multicellular

• Too large for phagocytosis

• Biologically similar to host → harder to target

In general, what is the body’s strategy to eliminate a parasite?

• Physical expulsion:

  • Coughing, sneezing, vomiting, diarrhea

• Barrier defenses:

  • Increased mucus

• “Explosive” immune responses to dislodge parasites

What are the characteristics of ‘type 2’ immunity?

• Driven by TH2 cells

• Cytokines:

  • IL-4 → IgE production

  • IL-5 → eosinophils

  • IL-13 → mucus production

• Key cells:

  • Mast cells

  • Basophils

  • Eosinophils

• Dominant antibody: IgE