BIO-336 (Comprehensive)

Alpha-Beta T cells

Advanced; require MHC display; high diversity.

Gamma-Delta T cells

Ancient/Archaic; no display platform needed (similar to BCR); limited randomization.

T-Independent: speed and antibody class

Fast; always starts as IgM; no memory.

T-Dependent: speed and antibody class

Slower; can class-switch (IgG, IgA, IgE); full memory.

Where antigens from "inside the cell" (viral/cancer) are displayed

MHC I (activates CD8 CTLs).

Where antigens from "outside the cell" (engulfed) are displayed

MHC II (activates CD4 helpers).

Herd Immunity

When enough immune individuals exist in a population to protect those who are still vulnerable.

Explain the mechanism of a conjugate vaccine.

The B cell binds the carbohydrate, internalizes the complex, and displays the protein peptides on MHC II, allowing CD4 T cell help for class switching to IgG.

Give an example of a Herpes virus that hide in nerve cells and reactivates later.

VZV (Varicella-Zoster Virus); causes chickenpox initially and shingles later in life.

How do allergy shots utilize the concept of tolerance?

They exploit peripheral tolerance to down-regulate immunity to specific foreign antigens over time.

How does HIV cause AIDS if it doesn't directly damage all tissues?

HIV paralyzes CD4 T cells; without these "helpers," the person becomes vulnerable to opportunistic infections that are normally harmless.

How does Interferon help CTL activation?

It upregulates MHC I expression, forcing more viral peptides to be displayed.

How many proteins and peptides can a single virus produce?

A virus with ~12 proteins can be fragmented into dozens of peptides, providing an enormous range of targets.

Name the Antigen-Presenting Cells (APCs) that have MHC II and interact with CD4 cells.

1. B lymphocytes.
2. Macrophages.
3. Dendritic cells.

What does Type I (IFN-α, IFN-β) do?

Primary antiviral; shuts down protein synthesis.

What does Type II (IFN-γ) do?

TH1 response; pro-inflammatory.

What does Type III (IFN-) do?

Specific infections like influenza.

Name "Immune Privileged Sites" where cell-mediated immunity is restricted.

1. Inside the eye.
2. Central Nervous System (CNS).

Rank the Immunogenicity Hierarchy from most to least immunogenic.

Proteins → carbs → lipids → DNA/RNA

Roughly how many different T cells and B lymphocytes does the body generate?

Roughly half a billion (5 × 10⁸) different T cells and half a billion different B lymphocytes.

What "critical concept" describes the deletion of cells that accidentally recognize the body's own proteins?

Clonal deletion, which is the process of tolerance.

What antibody and cell type are critical for antiparasitic (worm) responses?

IgE and Mast cells (which release toxic compounds via FC-IgE receptors).

What are "Syncytia" and which cells are best at dealing with them?

Giant multinucleated cells formed by fused membranes (RSV); CTLs are specifically evolved to deal with them because antibodies cannot reach inside.

What are Monoclonal antibodies?

Laboratory-made (hybridoma); one specific antibody specificity.

What are Polyclonal antibodies?

Natural mixture in blood against every epitope exposed.

NKT cells regarding TCR and Antigen display

Have a TCR (alpha-beta) and require antigen display via CD1.

NK cells regarding TCR and Antigen display

Have no TCR and do not require antigen display.

What are the four types of co-stimulation?

1. MHC/TCR signal (High specificity).
2. CD4/CD8 co-receptor (Interaction with MHC platform).
3. B7/CD28 interaction (APC to T cell).
4. Cytokine dialogue (Bidirectional conversation).

What are the four types of hypersensitivity summary (by antibody/complement/cell)?

Type 1: IgE, Mast cells.
Type 2: IgG/IgM, Cell surfaces/Complement.
Type 3: IgG, Immune Complexes/Neutrophils.
Type 4: None (T-cell), Delayed days/weeks.

What are the similarities between T cell receptors (TCRs) and B cell receptors (BCRs)?

1. Both are randomized in their receptor region.
2. Both require activation and clonal amplification before responding.

What are the three display platforms on a dendritic cell and what do they display?

1. MHC I: Peptide only.
2. MHC II: Peptide only.
3. CD1: Glycolipid (not peptide).

What are the three laboratory methods mentioned for determining MHC structure?

1. X-ray crystallography (Gold standard).
2. Cryo-EM.
3. NMR.

What are the three sources of MHC diversity?

1. Polymorphism (many alleles in population).
2. Polygenic (multiple genes per person).
3. Codominance (maternal and paternal alleles expressed simultaneously).

What are the two primary functions of CD8 T cells?

1. Cytotoxic T Lymphocyte (CTL): Targets virally infected or cancer cells.
2. T Suppressor: Suppresses inappropriate immune/inflammatory responses.

What are the two roles of NK cells in the antiviral phase?

1. Kill cells with low MHC I expression.
2. ADCC (Antibody-dependent cellular cytotoxicity).

What are the two steps of T cell selection in the thymus?

1. Positive Selection: Keep cells that interact "a little bit" with self-MHC.
2. Negative Selection: Delete cells that interact "too strongly" with self-peptide (prevents autoimmunity).

What are the two theories for why MHC diversity is so high?

1. Heterozygous Advantage: Carrying different alleles allows for more diverse peptide display.
2. Population-level Diversity (Disassortative Mating): Ensures some individuals survive any pandemic.

What are the two types of tolerance, and when/where do they occur?

1. Central tolerance: During gestational (fetal) life in primary lymphoid tissue.
2. Peripheral tolerance: Throughout the rest of life in secondary lymphoid tissue.

What are the viral immune evasion strategies?

1. Cover with host-derived membrane.
2. Hide inside cells (syncytia).
3. Evolve molecular mechanisms to block immune functions.

What cell marks the shift/bridge from innate to adaptive immunity?

Dendritic cell (the only cell that can initiate a response from a naive CD4+ T cell).

What do CD8 CTLs use to kill targets after forming an immune synapse?

FAS ligand (and perforin/granzymes which cause "clean" death/apoptosis).

What happens to an MHC molecule without a peptide in its binding pocket?

It falls apart.

What is "Affinity Maturation"?

Hypermutation in B cell genes specifically encoding the antibody binding site, resulting in higher-affinity antibodies over time.

What is "Alloreactivity," and what percentage of CTLs participate?

The interaction between a recipient's CTLs and a donor's cells; ~10% of CTLs can react with any given foreign MHC, causing rejection.

What is "Antibody Enhancement" (Antibody-Dependent Enhancement)?

When non-neutralizing antibodies from a first infection increase the chance of the second infection getting inside cells (e.g., Dengue fever).

What is "Cross-Presentation"?

An exception where a dendritic cell engulfs a dying cell from the outside but displays the peptide on MHC I to activate CTLs.

What is "Diapedesis" or "Extravasation"?

The process where immune cells squeeze through vessel walls to enter tissue at an infection site.

What is "Disassortative Mating" in the context of MHC?

Evidence suggests individuals are attracted to people with different MHC haplotypes (mediated by pheromones/smell).

What is "HLA Typing"?

The scientific process of matching tissue donors to recipients, often done with flow cytometry.

What is "Reversion" in live attenuated vaccines?

When a weakened vaccine strain mutates back to the original virulent "wild type" (e.g., oral polio vaccine).

What is "The Proteasome" analogous to in these notes?

A "wood chipper" that chops worn-out or viral proteins into peptides (   amino acids) for MHC I loading.

What is considered the third and final level of immunity?

The antigen-specific response.

What is Rhogam and how does it prevent hemolytic disease of the newborn?

It is IgG specific for RhD antigen; it opsonizes fetal blood cells in the mother's circulation so they are destroyed before her immune system can mount a memory response.

What is the "Anamnestic response"?

The logarithmic (4 orders of magnitude) amplification of immune function during a secondary infection.

What is the "Antiviral State" triggered by Interferon?

Interferon shuts down protein synthesis in the cell to halt viral replication; it damages tissue but protects neighbors from spread.

What is the "best student answer" for why we have B and T cells?

"B cells patrol the outside of the cell, T cells patrol the inside."

What is the "exception" to the rule that alpha-beta TCRs recognize peptides?

At CD1, where alpha-beta TCRs recognize glycolipids.

What is the "Red Queen Hypothesis" in immunology?

The idea of an immunological arms race: pathogens evolve to block defenses, and hosts evolve new defenses just to "keep in the same place" (survive).

What is the "unusual property" of thymic cells during gestation?

They express every protein the genome can encode to ensure no T cells react to self-peptides.

how TCRs recognize antigens

Can ONLY bind antigen if displayed on MHC I or MHC II ("silver platter").

how BCRs recognize antigens

Can bind antigen freely floating in blood or lymph.

Antigen

Individual protein.

Hapten

Molecule too small to immunize alone; must be coupled to a carrier.

Neutralizing antibodies

Blocks the virus from attaching to tissue (prevents infection).

Non-neutralizing antibodies

Binds the virus but may not protect.

What is the end product of T cell activation?

Cytotoxic killing or helper functions.

What is the function of IL-2?

It stimulates cell division and drives clonal selection and amplification during infection.

What is the primary target of NK cells (Natural Killers)?

Cells with low MHC I expression and antibody-coated cells.

What is the primary target of NKT cells?

Mycobacterial infections (e.g., TB, leprosy).

What is the result of a malfunction in the antigen-specific immune response?

Autoimmunity, where the immune system attacks the body's own tissue.

What is the role of the CD40/CD40 ligand interaction?

It is an additional form of co-stimulation important in antibody production.

What is the role of the Invariant chain (Ii) and CLIP in MHC II?

Ii keeps the binding cleft intact during synthesis; it is trimmed to CLIP, which is removed only when the actual peptide is ready to be loaded.

What is the single most important antiviral mechanism?

CD8 CTLs (Adaptive); though Interferon is the most important early mechanism.

What is the starting point (phenotype) for all CD helper cells before differentiation?

TH0.

Structure of TCR

Alpha-beta heterodimer.

Structure of BCR

Membrane-bound antibody molecule.

What is the theoretical recognition capability of a unique TCR?

Each unique TCR can, in theory, recognize a different peptide (antigen).

What killing mechanism involving a ligand is expressed by all killer cells (NK, NKT, CTL)?

FAS ligand.

What major threat to immunological memory can "wipe out years" of stored immunity?

Measles; the virus directly attacks memory cells and other immune cells.

What molecular system in the thymus causes the expression of every protein the genome encodes?

AIRE (AutoImmune REgulator).

What molecule is the most potent pro-inflammatory trigger for an antiviral response, and why?

Double-stranded RNA (dsRNA); human cells never produce it, but most viruses do, making it a perfect alarm signal.

What signal do infected or damaged cells display to indicate they are ready to be destroyed?

FAS receptor (the "please kill me" signal).

What three steps occur after a BCR is bound by its antigen?

1. Clonal selection and clonal amplification.
2. Production of soluble antibodies.
3. This occurs only after activation.

What unique component makes each T or B cell different from the others?

Only the receptor protein: the T cell receptor (TCR) or the B cell receptor (BCR).

What was Maurice Hillman's solution to making carbohydrate vaccines "boostable"?

Carbohydrate-Protein Conjugate Vaccine: Covalently coupling the carbohydrate to a protein carrier.

What was the conclusion of the Zinkernagel and Doherty "MHC Restriction" experiment?

The TCR recognizes BOTH the peptide AND the MHC display platform; CTLs will only kill if the MHC haplotype matches what they were trained on.

What was the first intentional vaccine, and who developed it?

The Smallpox vaccine by Edward Jenner (using cowpox).

Where do CD4 and CD8 bind on the MHC molecule, and what are they called?

They bind to the back side of the MHC pocket; they are called co-receptors.

Which cell is described as "central" because it has three display platforms?

The dendritic cell.

Which cells recognize MHC I?

CD8 T cell.

Which cells recognize MHC II?

CD4 T cell.

Which cells recognize CD1?

NKT cell.

Which cytokine drives CD4 T cells toward TH2 and TH17 phenotypes?

TH2: IL-4.
TH17: IL-17.

Which cytokine drives CD4 T cells toward the TH1 phenotype, and what is its role?

Interferon-gamma (IFN-  γ); it is the strongest pro-inflammatory cytokine.

Which receptor likely evolved first: BCR or TCR?

B cell receptor (BCR); the TCR is useless without MHC, implying they had to co-evolve simultaneously.

Which T helper phenotype is critical for surviving a fungal infection?

TH1 (dominance suggests survival, while TH2 dominance suggests poor prognosis).

Which Toll-like receptor (TLR) detects dsRNA?

TLR3.

Who developed more than half of all vaccines used today and created the conjugate strategy?

Maurice Hillman.

Who/what is responsible for making you feel "sick" during an infection?

Interferon and other inflammatory molecules, not the virus itself.

Why are CTLs and CD4s restricted from privileged sites?

Their response is too damaging and would cause irreversible tissue damage.