Immunology Exam III Study Guide

Comprehensive review flashcards covering antibody structure and functions, T helper and regulatory subsets, B-cell development and activation, immunological memory and vaccines, mucosal immunity, and pathogen immune evasion mechanisms.

How do immunoglobulins differ from T-cell receptors in the types of antigens they recognize and their processing requirements?

Immunoglobulins can recognize proteins, carbohydrates, lipids, and nucleic acids in their native form without requiring prior antigen processing.

What is the structural difference between a linear epitope and a conformational epitope?

A linear epitope depends mainly on the primary sequence of monomers and may remain recognizable after denaturation, whereas a conformational epitope depends on the intact three-dimensional shape and is lost upon denaturation.

What is a multivalent antigen, and how does it influence antibody binding strength?

A multivalent antigen contains multiple epitopes; repeating copies of the same epitope permit multiple antibodies to bind simultaneously, thereby increasing the overall binding strength, or avidity.

What are the five antibody effector functions highlighted in the lecture?

Neutralization, opsonization, agglutination, complement / immune-cell activation, and antibody-dependent cellular cytotoxicity (ADCC).

How do the heavy-chain constant domains and hinge regions differ between IgG/IgA/IgD and IgM/IgE?

IgG, IgA, and IgD contain three heavy-chain constant domains plus a disulfide-stabilized hinge region, whereas IgM and IgE contain four constant domains and lack a conventional hinge.

What is the secreted form, primary anatomical location, and primary role of IgM?

IgM is secreted as a pentamer with a J chain, is primarily found in blood and lymphatic fluid, is the first isotype produced after initial B-cell activation, and provides strong classical complement activation, opsonization, and agglutination.

Which antibody isotype is the most abundant, can cross the placenta, and mediates long-term protection?

IgG.

Where is IgA predominantly located, and what is its primary protective function?

IgA is located at mucosal surfaces and in secretions like saliva, tears, and breast milk/colostrum, providing noninflammatory barrier protection through neutralization and agglutination.

How does IgE mediate defense against multicellular parasites and trigger allergic reactions?

IgE binds to granulocytes via high-affinity receptors; cross-linking of cell-bound IgE by matching antigen triggers cellular degranulation.

What key signals, target cell, and outcome define TH1-mediated help?

TH1 cells deliver IFN-gamma and express CD40L to bind CD40 on macrophages presenting matching antigen, resulting in macrophage activation, enhanced phagocytosis, and accelerated phagosome-lysosome fusion.

What key cytokine is produced by TH2 cells to mobilize eosinophils, and what is its effect?

TH2 cells produce IL-5, which provides indirect eosinophil activation to enhance parasite binding and toxic granule release.

Which signals and cytokines provided by TFH cells mediate cognate help to B cells?

TFH cells provide CD40L, IL-4, and IL-21 to promote B-cell activation, differentiation, and class switch recombination.

What cytokines are produced by TH17 cells, and what tissue function do they support?

TH17 cells produce IL-17 and IL-22, supporting mucosal barrier defense and local antimicrobial protection.

What transcription factor directs the regulatory program of Treg cells, and how does Treg-derived IL-10 suppress conventional T cells?

FOXP3 directs Treg suppression and supports production of IL-10, which suppresses transcriptional activity involving AP-1 and NFAT in conventional T cells.

What are the components of the B-cell receptor (BCR) complex, and what signaling motifs do they carry?

The BCR consists of membrane-bound immunoglobulin associated with CD79a and CD79b (Ig-alpha and Ig-beta), which contain immunoreceptor tyrosine-based activation motifs (ITAMs).

Which gene segments encode the variable regions of immunoglobulin heavy chains versus light chains?

Heavy-chain variable regions are assembled from V, D, and J gene segments, while light-chain variable regions are assembled from V and J gene segments.

What genetic alteration occurs during class switch recombination (CSR), and what property of the antibody is preserved?

DNA encoding heavy-chain constant regions is cut and rejoined to alter the constant region (changing effector function and distribution), while the original variable-region DNA and antigen specificity are fully preserved.

What do high pathogen-specific IgM versus IgG levels indicate regarding infection timing?

High IgM indicates a recent or acute primary infection, whereas high IgG indicates a past infection or established longer-term immunity.

Which antibody isotype rises fastest during secondary exposure to a parasitic infection?

IgE.

How do central memory T cells (TCM) differ from effector memory T cells (TEM) in localization and immediate effector function?

TCM reside primarily in lymphoid organs, are long-lived, and differentiate into effector-memory cells, whereas TEM reside mostly in peripheral tissues (e.g., skin and mucosa) and are directly functional effector cells.

What are the distinguishing properties of resident memory T cells (TRM)?

TRM reside long-term within peripheral tissues without recirculating through blood or lymphoid organs, providing immediate localized protection.

Which inhibitory receptor on naïve B cells mediates negative feedback when pre-existing antibody levels are high?

FcγRIIB1.

What mechanisms of immune stimulation are provided by CpG oligonucleotides, MF59, and aluminum salts in vaccines?

CpG oligonucleotides mimic bacterial DNA to activate TLRs; MF59 (an oil-in-water emulsion) elevates IL-1 and TNF-alpha; aluminum salts promote TFH cell responses and antibody production.

Match the following vaccine examples to their corresponding platform: Hepatitis A, MMR, HPV, and Johnson & Johnson COVID-19.

Hepatitis A is an inactivated vaccine, MMR is a live attenuated vaccine, HPV is a subunit vaccine, and Johnson & Johnson COVID-19 is a recombinant viral vector vaccine.

What are the anatomical inductive sites versus effector sites in intestinal mucosal immunity?

Inductive sites are Peyer's patches and mesenteric lymph nodes; effector sites are the lamina propria and the intestinal epithelium.

What antimicrobial substances are secreted by Paneth cells residing in intestinal crypts?

Alpha-defensins, lysozyme, REG3 lectins, and other antimicrobial products.

What is the primary role of microfold (M) cells in mucosal immunity?

M cells transcytose intact lumenal antigens across the follicle-associated epithelium to deliver them to underlying dendritic cells; M cells do not act as antigen-presenting cells themselves.

What molecular signals are required for T-dependent versus T-independent mucosal IgA class switching?

T-dependent switching requires CD40L-CD40 engagement plus TGF-beta; T-independent switching is driven by BAFF, APRIL, and TGF-beta.

How does dimeric IgA cross mucosal epithelium into the lumen, and what provides its protection in secretions?

Dimeric IgA binds the polymeric immunoglobulin receptor (pIgR) on the basolateral surface and undergoes transcytosis; cleaved pIgR remains bound as the secretory component to protect IgA from enzymatic degradation.

How do human cytomegalovirus (HCMV) proteins US2, US3, US6, and US10 disrupt MHC class I presentation?

US2 directs MHC I heavy chains to degradation, US3 impairs peptide binding, US6 blocks TAP-dependent peptide transport into the ER, and US10 retains MHC I within the ER.

What immune consequence can occur if a pathogen extensively downregulates surface MHC class I to evade CD8 T cells?

Severe loss of surface MHC class I eliminates inhibitory receptor signaling on Natural Killer (NK) cells, triggering missing-self recognition and NK-mediated lysis.

Which three encapsulated bacterial species are highlighted as using their capsules to reduce C3b complement deposition?

Klebsiella pneumoniae, Streptococcus pneumoniae, and Neisseria meningitidis.

How does Listeria monocytogenes evade destruction within macrophage phagosomes?

It secretes listeriolysin O, a pore-forming toxin that lyses the phagosomal membrane and releases the bacterium into the cytoplasm.

What bacterial factors allow Mycobacterium tuberculosis to block phagosome-lysosome fusion?

PknG and SapM.

By what mechanism does the VacA toxin of Helicobacter pylori inhibit T-cell proliferation?

VacA impairs $Ca^{2+}$ signaling and calcineurin activity, preventing NFAT nuclear translocation and reducing IL-2 transcription.

How do superantigens induce massive, non-specific T-cell activation?

Superantigens cross-link the outer surface of MHC class II molecules with selected TCR V-beta segments outside the conventional antigen-binding groove, activating polyclonal T cells regardless of peptide specificity.

What is the distinction between antigenic polymorphism and antigenic variation?

Antigenic polymorphism refers to stable genetic antigen differences between distinct strains, whereas antigenic variation involves a single pathogen lineage systematically altering its expressed surface antigens over time during an active infection.

Which specific surface antigens undergo switching in Trypanosoma brucei, Plasmodium falciparum, and Neisseria gonorrhoeae?

Trypanosoma brucei switches VSG (variant surface glycoprotein), Plasmodium falciparum switches var-gene expression, and Neisseria gonorrhoeae alters pilin expression.