M9: Immunological Memory and Vaccines

What does the first encounter with an antigen do?

Produce a primary immune response involving the innate immune responses and activation of naive lymphocytes

What is considered a successful primary immune response?

Reaches 2 goals:

1. Produce powerful effector cells and antibodies to quickly clear infection

2. Produce memory B and T cells to provide long-term immunological memory

What is triggered by a reinvasion of the same pathogen?

A secondary immune response that is faster and stronger (not adaptive yet)

What are the stages of adaptive immune response?

0) Establishment of infection and activation of innate immune response

1) Induction of adaptive response and expansion

2) Contraction

3) Immunological memory

4) Induction of secondary immune response

What cell is responsible in the contraction phase?

Treg

Who had the first surviving immunological memory record?

Thucydides during Athens plague in 430 BC

Who was one of the first to write an epidemiology study?

Peter Panum regarding measles

What was the first vaccine to be invented?

Smallpox by Dr. Edward Jenner

• variolated farmer’s son with fluid from cowpox pustules

Which statement best describes the role of long-lived plasma cells in maintaining steady-state antibody levels?

Long-lived plasma cells continuously secrete antibodies, providing baseline protection without requiring repeated antigen exposure, mostly from the bone marrow

Which of the following best describes the difference between effector cells during a primary and secondary immune response?

The secondary immune response produces effector cells more rapidly and in greater numbers than the primary immune response.

What T cell does NOT make any memory cells?

Treg, unlike Th

Which inhibitory receptor on naïve B cells plays a role in regulating the primary immune response, and what is its function?

FcγRIIB; it inhibits B cell activation when immune complexes bind, helping to prevent excessive immune responses.

How does IgM play a part in regulating the primary immune response of B cells?

Naive B cells have low affinity IgM that, with a high affinity IgG, forms immune complexes that prevent activation of more naive B cells

What happens if a naive B cell binds to a pathogen EARLY in a primary response?

Naive B cell is activated to become an antibody producing plasma cell → plasma cell secretes low affinity IgM

What happens if a naive B cell binds to a pathogen LATE in a primary response?

Naive B cell receives a negative signal from Fc receptor → naive B cell is induced to die

What happens if a memory B cell binds to a pathogen in a secondary response?

Memory B cell is activated to become an antibody-producing plasma cell → plasma cell secretes high affinity IgG

What is the difference in receptors of a naive vs memory B cell?

Naive: low affinity IgM and FcγRIIB

Memory: high affinity IgG and no inhibitory receptor

How do immune complexes help prevent hemolytic disease of the newborn, and what is the role of RhoGAM in this process?

RhoGAM contains anti-Rh antibodies that create immune complexes with fetal Rh+ RBCs, engaging inhibitory Fc receptors on maternal B cells to prevent activation.

What is the demographic of those affected by hemolytic anemia?

RhD- mother carrying RhD+fetus

What is the outcome of the FIRST pregnancy of an RhD- mom carrying RhD+ fetus?

Fetal RhD binds to maternal BCR →  produces low affinity IgM/IgG as primary response

• minor fetal RBC destruction occurs

• overall healthy newborn

What is the outcome of the SECOND pregnancy of an RhD- mom carrying RhD+ fetus?

Fetal RhD binds to maternal BCR →  produces high affinity IgG as primary response into placenta via transcytosis

• massive fetal RBC destruction occurs

• anemic newborns

What does the first injection of RhoGAM do?

Find any potential fetal RBCs in mom’s circulation, coats erythrocytes

• Prevents BCR binding by displaying high affinity IgG that binds to inhibitory receptor to make B cell go through apoptosis

What does the second injection of RhoGAM do?

Protects against fetal rbc that entered maternal circulation during labor

How do the 4 subsets of long-lived plasma cells differ?

• Glycoprotein expression (A-D)

• varying levels of CD19, CD38, and CD138

What types of cells make up serological memory? and for what pathogens?

Steady state long-lived plasma cells; pathogens that do not mutate rapidly

What happens to immune responses in the case where pathogens evolve rapidly?

1) Primary immune response produces antibodies with a particular epitope specificities

2) Epitopes mutate rapidly even inbetween infections

3) High affinity IgG during a secondary immune response suppresses activation of new naive B cells

• This even applies if you have at least 1 of the epitopes

How does mTORC1 expression and asymmetric cell division influence naïve T cell activation and differentiation?

Asymmetric cell division leads to differential mTORC1 expression, generating distinct daughter cells that contribute to both effector and memory T cell populations.

What T cells can be derived from CD4 and CD8 respectively?

CD4 → TFH, TH1, TH2, TH17

CD8 → cytotoxic

How do naive T cells survive pre-activation?

Using catabolic starvation metabolism such as autophagy/mitophagy

• Has the bare minimum organelles to survive

• Uses slow forms of ATP production (oxidative phosphorylation and fatty acid oxidation)

What happens to naive T cells once it gets activated?

Undergoes metabolic reprogramming

• Switches to faster forms of ATP production like glycolysis

• regulated by mTORC1 protein kinase

What is mTORC1’s function?

A protein kinase (phosphorylates) that controls metabolic reprogramming and differentiation

What is the process of asymmetric cell division?

1) Naive CD8 T cell is activated by specific antigen

2) Antigen-activated CD8 T cell is reprogrammed and enters mitosis

3) CD8 T cell undergoes asymmetric division

4) Each naive T cell activated gives rise to one effector (the one with more mTORC) and one memory cell

When does it switch from asymmetric to symmetric

First several mitotic divisions = asymmetric

Followed by symmetric cell division to produce a large population of pathogen-specific effector T cells

Later rounds of mitosis focus on producing memory cells (slow dividing starving T cells)

What is the significance of asymmetric division?

During the clonal expansion, this gives us different populations of T cells

TCM Cells

Central memory T cells

• express L-selectin and CCR7

• allows them to enter secondary lymphoid tissues

• limited effector function but high capacity for IL-2 secretion, proliferation, differentiation into effector T cells

TEM cells

Effector memory T cells

• express chemokine receptors (CCR4-6, CXCR3)

• use chemotaxis to enter peripheral tissues

• response immediately to infection at site of origin (become follicular helper or cytotoxic T cells)

What are two major differences that made memory T cells easier to activate than naive T cells?

1) Memory T cells don’t require CD28 co-stimulation (just MHC recognition)

2) Memory T cells have a shorter CD45 tyrosine phosphatase

What is difference of CD45 in naive and memory T cells?

CD45 removes inhibitory phosphate on Lck → TCR ζ chain

• naive cells have CD45RA (longer, more time to activate)

• memory cells have CD45R0 (shorter thus better interactions with TCR)

Name the 2/3 T cells that circulate in the body and 1/3 that doesn’t.

Circulating: TCM + TEM

Noncirculating: TRM

TRM

Slow dividing memory T cells post-infection that enter the tissue and become incorporated as sentries.

• remain in that tissue and never return to circulation

• in highest concentration in epithelial barrier tissues (skin, lungs, gut, genitourinary tract)

All primary immune responses begin in ___, even when the infection is in peripheral tissues.

secondary lymphoid tissues

What would be the classifications that correctly describe the type of immunity a baby receives from breastfeeding?

Naturally acquired immunity + passive immunity

What are some ways a person can receive active immunity?

Natural encounter of infection or artificial vaccines (activate B/T cells to make memory cells for pathogen)

What are some ways a person can receive passive immunity?

Natural maternal antibodies or artificial monoclonal antibodies (movement of antibodies from one person to another)

What are vaccines used for?

To artificially expose our immune system to pathogens or their antigens to induce an active primary immune response

What are the 6 types of vaccines?

1) Inactive

2) Live-attenuated

3) Subunit

4) Toxoid

5) Viral vector

6) mRNA

Why are memory T cells more easily activated than naïve T cells?

Memory T cells require less co-stimulation than naïve T cells and express CD45RO, which enhances TCR signaling.

Which statement best describes the distribution of different memory T cell populations in the body?

Tissue-resident memory T cells are found in peripheral tissues, such as the skin and mucosa, where they provide localized immunity.

Which type of vaccine uses pathogenic subunits and adjuvants, and why are these components included?

Conjugate or subunit vaccines use subunits of the pathogen along with adjuvants to enhance the immune response and increase the durability of immunity.

• Alum

• Acellular Bordetella pertussis in DTaP

What are inactivated vaccines?

“Wild” viruses/bacteria that have been inactivated using radiation/heat, e.g. influenza

What do inactivated vaccines target?

Body’s antibody production of high affinity antibodies

What are live, attenuated vaccines?

“Wild” viruses/bacteria that are weakened by mutation, e.g. MMR

What do live, attenuated vaccines target?

The immune system directly, strong enough to trigger a immune response but too weak to cause disease

What are subunit vaccines?

Contains the whole pathogen with the conjugate on it or just that polysaccharide with the protein attached  e.g. HBV and meningitis

What do subunits target?

APC cells to be presented to immune cells and trigger an immune response (not innate immune response tho)

What are toxoid vaccines?

Neutralize the toxin activity created by bacteria, instead of the harmful bacteria itself e.g. diphtheria and tetanus

What do toxoid vaccines target?

Toxic activity, creating an antibody response to that toxin

What is a viral vector vaccine?

Made of a small section of a virus’ genetic material in a harmless viral capsule to attach to cell to be transcripted/translated into proteins to be recognized by immune cells e.g. COVID (J&J)

What is mRNA vaccine?

Made of a small section of a virus’ genetic material in a nanoparticle that docks with cell and lets mRNA in to be transcripted/translated into proteins to be recognized by immune cells (Pfizer)

What is a vaccine’s effectiveness in an acute vs chronic infection?

Acute: highly effective i.e. Hepatitis A/B, Flu, TDaP

Chronic: more difficult i.e. HIV, Measles, Tuberculosis