MICROIMM

2500A

Adaptive
Immunity

Dr. Veronica Guariglia

Sep 19th 2022
Adaptive Immunity
IMMUNE SYSTEM

Innate Adaptive
Immunity Immunity

Barriers
T-cell B-cell
Cells
immunity immunity
Immune signaling

Janeway's Immunobiology, 10e

Adaptive Immunity
INNATE IMMUNITY ADAPTIVE IMMUNITY

Main Cells Phagocytes; natural killer cells

Proteins proinflammatory cytokines, type I IFN,

chemokines

Mechanism of pathogen Phagocytosis; Apoptosis; chemical

destruction attack by antimicrobial peptides
Immune response Non-adaptive: same response for
(adaptive or non-adaptive) every exposure to identical pathogen
Response time Rapid (seconds, minutes, hours)
Memory No memory is formed

Efficiency Rarely malfunctions

Learning Objectives
By the end of this lecture, you should be able to:

1) Contrast the kinetics of a primary vs a memory immune response.

2) List the primary lymphoid tissues important for B and T cell development.

3) List and state the importance of each type of secondary lymphoid tissue in
adaptive immunity.

4) Define the terms: antigen, epitope, clonal expansion.

5) Define the structure of B and T cell receptors.

Main Cells of Adaptive Immunity
B cells
• antibodies important against
extracellular pathogens

T cells
• helper T cells (Th cells; CD4+ T cells) important against
• cytotoxic T cells (CTL; CD8+ T cells) intracellular pathogens
Primary Vs Memory response
Memory
Primary response: First
exposure to pathogen.

Secondary response:
Subsequent exposure to the
same pathogen.
- Larger
- Faster

It’s “adaptive” since the

immune response is more
efficient with re-exposure to
an identical pathogen
(memory).
Primary Immune Response Remember innate and adaptive responses
are not mutually exclusive!

FIRST EXPOSURE:
natural infection or
vaccination

Janeway's Immunobiology, 10e

Immunological Memory

Created with BioRender

Immunological Memory Naïve cell

“Naïve” B/T cells can

differentiate into:
Memory
Effector cells: precursor

B cells → Plasma cells Effector

cell

T cells → Helper T cells

→ Cytotoxic T cells

Memory cells: remain after

infection is resolved. Memory cell

Omilusik and Goldrath. The origins of memory T cells. Nature. 2017

Immunological Memory

Immunological
memory is the basis
of vaccination!

Natural Created with BioRender

exposure
Vaccination
Immunological Memory
and Vaccines

Janeway's Immunobiology, 10e

Summary
Key Features of Adaptive Immunity:
- Memory
- Specificity

First exposure (Primary Response):

• Naïve B & T cells bind to pathogen

• Effector and memory B & T cells are generated

Subsequent exposure (Secondary or memory response):

• Memory B & T cells respond

• More effectors B & T cells are generated
Lymphoid Tissue
Primary Lymphoid Tissue:
(where lymphocytes are developed)
- Thymus (T cells)
- Bone Marrow (B and T cells)

Secondary Lymphoid Tissue:

(where naïve lymphocytes are further
differentiated)
- Lymph nodes
- Spleen
- Mucosa-associated Lymphatic Tissue
(MALT)
Lymphatic System
Lymphatic System

Network of tissues, vessels and

organs that work in close
proximity with the circulatory
system

Lymph: interstitial tissue fluid

that enters the lymphatic
vessels to be transported back
into the blood.
Lymphatic System
Lymphatic capillaries run parallel to blood
capillaries in all body tissues.

When lymph leaves these tissues it carries

waste products from tissues including dead
cells, CO2, and pathogens.

Lymph then passes and filters through lymph

nodes.

https://www.nursingtimes.net/

Lymph nodes are the perfect spot for immune

cells to “look for” pathogens.
Lymphatic System Why inject vaccines into muscle?

Vaccine injections

Typically intramuscular, on the arm:

Good blood flow
Optimizes immune response

Other routes of administration:

Subcutaneous (infants)
Orally (Rotavirus vaccine)
Nasally (Flu vaccine)

Injected vaccine components travel in

the lymph to the nearest lymph nodes
(typically in the arm pits).
https://www.vaccinestoday.eu/
Lymphoid Tissue

- B cells develop in the bone marrow

- T cells start to develop in the bone marrow

and finish developing in the Thymus.
 Primary Lymphoid
Tissue

Created with Biorender

Created with Biorender Th CTL

SLT - Lymph Nodes

B cell
zone

T cell
zone

Janeway's Immunobiology, 10e

Lymph Nodes
Colocalization of T cells and B cells at the
follicular border.

(A) B cells are stained brown.

(B) T cells are stained brown.

Garside P, et al. 1998. Science.

SLT - Spleen
Not actually in the lymphatic system

But it filters blood.

Shows similar B/T cell organization
(where they meet blood-borne
pathogens)

B cell follicle

T cell zone

Janeway's Immunobiology, 10e

 SLT- MALT Mucosa-associated Lymphoid Tissue

Microfold cells (M cells)

Site where B and T cells meet
pathogens in mucosal areas.

Found in oral-pharyngeal cavity

and gastrointestinal, respiratory,
urogenital tracts.

MALT located in tonsils, lungs,

colon, appendix, etc.

M cells help transport antigens

into the tissue
Janeway's Immunobiology, 10e
Tonsils Frequently swollen in childhood due to infections from
many first-time pathogens.

Tonsils can be removed.

Does a tonsillectomy compromise immunity?

B-cell and T-cell Receptors
- Naïve T cells and B cells (from Thymus and Bone marrow, resp.) enter
circulation and migrate to SLTs in search of pathogens.

- T/B cells express surface receptors that recognize and bind to a

pathogen/antigen.
T-cell Receptor B-cell Receptor
(TCR) (BCR)

Immunoglobin
molecule

Created with Biorender

B-cell and T-cell Receptors

T cell Receptor B cell Receptor

Created with Biorender

Antigens
An antigen is any substance that the variable
region of a BCR/TCR can bind to.
bacteria virus

Influenza virus

a microbe expresses many copies of

its own unique antigen(s)

Created with Biorender

Antigens
Antigens not only refer to microbes. They can be from our own cells as well.
For example:

A person’s blood type is determined based on the decorations (antigens) on their blood cells (A, B,
and Rh)

https://www.thetech.org/ask-a-geneticist/blood-type-and-pregnancy
Antigen and Epitope
An antigen is a macromolecule that
reacts with components of the immune
system. A given antigen may contain
several motifs that are recognized by
immune cells. Each motif is an epitope.
https://opentextbc.ca/biology/chapter/23-2-adaptive-immune-response/

The variable region of a BCR/TCR

binds to one unique epitope based
on structural fit.

Created with Biorender

Antigen Vs PAMPs

A given PAMP is expressed An antigen is a molecular

by a wide variety of structure that is generally
pathogens and is recognized unique to a specific pathogen
by PRRs (innate response). and is recognized by a specific
Example: LPS in Gram Neg. Primer to the Immune Response (Second Edition), Academic Cell, 2014.
antigen receptor (BCR/TCR,
adaptive response).
Example: H1N1 influenza
Antigen Recognition
Shape and size of the antigen would determine specificity of recognition by
antigen binding site of the receptor

Janeway's Immunobiology, 10e

Antibodies can recognize linear (exposed)

or conformational determinants in folded
proteins.
Janeway's Immunobiology, 10e
B cell receptor and antibody - have the same antigen specificity

- can bind pathogen directly

Janeway's Immunobiology, 10e

T cell receptors
Need antigen to be “presented” to them.

TCR

MHC

Created with Biorender

Diversity of B and T cell receptors
BCRs and TCRs have two variable regions.
BCR: heavy-chain variable region (VH) and the light-chain variable region (VL)
TCR:Vα and Vβ regions.
Variable regions are encoded in gene
BCR TCR segments of only part of the receptor
domain.

Segments are rearranged through

somatic DNA recombination (gene
rearrangement) to form a unique variable
region coding sequence.
Diversity of B cell receptors
BCR/Immunoglobins

Janeway's Immunobiology, 10e

~ 1013 possible unique BCRs

Janeway's Immunobiology, 10e

Diversity of T cell receptors

Janeway's Immunobiology, 10e

~ 1013 possible unique BCRs

~ 1018 possible unique TCRs

B and T cells make surface receptors

unique to each individual, which are
then not passed on to offspring.
Janeway's Immunobiology, 10e
Diversity of B and T cell receptors
Both B and T cells express many exact copies of a receptor with a unique antigen
binding site. This is the basis for adaptive immunity specificity!

https://bio.libretexts.org/
B and T cell receptor specificity

Each B-cell expresses a BCR with a variable

region specific for one unique peptide

Each T-cell expresses a TCR with a variable

region specific for one unique peptide

https://oncologypro.esmo.org/
Clonal Selection/Expansion of B and T cells
- T and B cells develop in primary lymphoid organs
(bone marrow for B cells and thymus for T cells).

- Naïve T and B cells express many copies of a surface

receptor that binds to one particular antigen.

- Different clones of T and B cells go through a deletion

process to weed out self-recognizing receptors.

- Remaining cells enter circulation to SLT where they

can interact with antigens/pathogens.

- If specific antigen is encountered, that cell proliferates

to create and army of cells with the same specificity
(clonal expansion).
Clonal Expansion of B and T cells

CLONAL
EXPANSION respond to the
pathogen
some remain as
memory T cells
most die via
apoptosis

Created with BioRender

Memory B and T cells – Immunological memory

Immune
response

Faster
Stronger

Janeway's Immunobiology, 10e

Innate Vs Adaptive receptors

expansion
Summary
Summary
Summary

Where will an adaptive immune response most likely be initiated

after an intramuscular arm injection of the Pfizer COVID-19
vaccine?

A) Tonsils
B) Thymus
C) Lymph nodes in the armpit
D) Site of injection
Summary

What properties do T cell receptors and antibodies have in common?

A) They are both secreted

B) They both bind directly to an antigenic epitope
C) They both recognize pathogen-associated molecular patterns
(PAMPs)
D) They both contain a variable region and a constant region
Next Lecture
1. Innate Immunity
Part 1: Barriers of Infection
Part 2: Cellular Response
Part 3: Innate Signaling
2. Introduction to Adaptive Immunity
3. T cell Immunity
4. B cell Immunity