Overview of

Adaptive
Immunity

Joshua Koenig, PhD

Department of Medicine
koenigjff@mcmaster.ca
Immediate innate Minor tissue
immune response: damage is
0-4 hours caused and
repaired
Immediate innate Minor tissue
damage is
0-4 hours caused and
repaired

Moderate
Induced innate
tissue damage
immune response:
is quickly
4 hours to 4 days
repaired
 Immediate innate Minor tissue
immune response: damage is
0-4 hours caused and
repaired

Moderate
Induced innate
tissue damage
immune response:
is quickly
4 hours to 4 days
repaired

Adaptive immune
response: 4 days until Major tissue
defeat of the pathogen, damage is
defeat of the host, or gradually
the compromise of repaired
chronic disease

YOU ARE HERE!

 Innate Immune Cells

Macrophage Eosinophil NK cell

Monocyte

Basophils
Adaptive Immune Cells

Lymphocytes
Regulatory

CellCartoons.net
What makes these cells adaptive?

Remember Paul Ehrlich?

1) This immune system reacts and

adapts to pathogens.

2) The functions of these cells are not

innate, they are instructed!
Key principles of both innate and adaptive immunity

IMMUNE RECOGNITION Detect the invader.

IMM““E PH“TEG“““ Mount a killing response.

IMMUNE REGULATION e repone !

Limit the response from
 Specificity inherited in the genome Yes No

Expressed by all cells of a particular type Yes No

(e.g. macrophages)

Triggers immediate response Yes No

Recognizes broad classes of pathogens Yes No

Interacts with a range of molecular structures Yes No

of a given type

Don’t worry about these yet.

Able to discriminate between even closely related No

molecular structures Yes

Figure 3.1 Janeway'’s Inmunobiology, 8ed. (© Garland Science 2012)

Adaptive immune receptors are

ANTIGEN SPECIFIC
Adaptive immune receptors are

ANTIGEN SPECIFIC

N
ANTIbody GENerating substance
Adaptive immune receptors are

ANTIGEN SPECIFIC

N
ANTIbody GENerating substance

Virtually anything can be an antigen

- Proteins
- Carbohydrates
- Nucleic acids
- Some small molecules
Adaptive immune receptors are

B cell receptor T cell receptor

Antibody receptor

B cell T cell
Immune Recognition

How do BCRs detect antigen?

* B cell receptor aka immunoglobulin aka antibody
* B cell receptors bind whole antigens in the conformation that they are found in nature.

Surface immunoglobulin
or B-cell receptor
antigen-binding

Antigen

transmembrane
region

Figure 1.17 The Immune System, 4th ed. (© Garland Science 2015)
 How do BCRs detect antigen?
* Each antibody has a different specificity! o
Binding?
* We refer to antibodies as anti- (antigen)
* E.g. anti-influenza antibody Yes No

antigen-binding sites

M variable
region
N hinge
M constant region
region
Antigens have epitopes
* Epitope- a small portion of the antigen that is directly bound by a B/T cell
receptor.

antigen-binding sites

M variable
region
N hinge
M constant region
region
Antigens have epitopes
* Linear epitopes are sequential amino acids (primary structure)
* Conformational/discontinuous epitopes are only present when the protein is
folded (secondary, tertiary, quaternary structure)

antibody antibody

F I\
protein antigen protein antigen
| am going to tell you more about B cells
and antibodies in later lectures!
 cell receptors do NOT bind whole, intact
antigens.

T cell receptors bind processed antigens,

presented by antigen presenting cells.
The simple version
Teell

TR

This can be any protein!

Processed

_ _ _ e e

@
e | .
plasma
membrane ’. J\ J\
S TCR . .
rJ

rI
=
=

or.

antigen-presenting cell

@
fi

Recognition
Figure 5.35 The Immune System, 4th ed. (© Garland Science 20
Immune Protection
Comparison of Innate and Adaptive
Innate Adaptive

Immediate killing Delayed response

Direct killing Direct and indirect killing

T cells: induce apoptosis, help innate cells kill

Phagocytosis, degranulation, induce apoptosis B cells: secrete antibodies which neutralize and
help innate cells engage in killing

Activation on first antigen encounter,

Killing on first antigen encounter . .
g g killing on second antigen encounter.*

* Not two separate infections, but the same cell must see the antigen twice during the same infection.
Immune Protection CellCartoons.net

wo major classes of T cells

CD4 “Helper” T cells CD8 “Cytotoxic” T cells

What the heck are CD4 and CD8?!

They are proteins found on the cell surface.

TCR
Immune Protection CellCartoons.net

wo major classes of T cells

CD4 “Helper” T cells CD8 “Cytotoxic” T cells

Provide signals which help other cells perform Directly kill infected or mutated host cells.
their functions.
 Immune Protection: CD8* T cells

CD8 T cell
CD8* T cells detect antigen
presented on MHC |

All nucleated cells express

TCR
MHC |
* This makes sense- all
cells need to be
Peptide
scanned for virus
proteins!
MHC class 1
When an infected cell is
detected, CD8* T cells kill
by inducing apoptosis.
Immune Protection
Immune Protection: CD4* T cells interact with
antigen presenting cells.
Hematopoietic

* CDA4*T cells detect antigen presented T cells

on MHCIII
B cells

. . TCR
* Only antigen presenting cells (APCs) Macrophages
express MHC 1. Peptide benariic colls

* Dendritic cells are the “professional Neutrophils

APC,” but other cells like MHC class 2 .
rythrocytes - -
macrophages, B cells can be APCs.
= I - Non-hematopoietic

tigen-presenting cell Liver hepatocytes + | -

Kidney epithelium + -

Brain + -t
CD4* T cells are specialized to help different cells.

T,1 cells T,2 cells T, 17 cells Ty, cells

Effector
CD4AT cell

Activate cellular Activate B cells

Enhance
Activate and antibody to refine the
Function neutrophil
macrophages response to antibody
response
parasites response
 B cells differentiate into plasma cells, which
secrete antibodies.

Antibodies

Bind and neutralize important regions

membrane- bacterium of the pathogen.
bound Ig plasma cells
0 Tag pathogens for destruction by the
innate immune system.
N N By 0
N, 0V
A & bA * S
Recru
fecrwt
| .
cgmp ement proteins to
seoreted antibody directly kill pathogens.

Among others!
Immune Protection

Where is adaptive immunity activated?

right subclavian vein left subclavian vein

Inactivated (naive) adaptive immune cells live at these tissues.

These tissues have “lymphoid” architecture- aka they look like

appendix large intestine
a lymph node.

lymphatics Immune cells come from the bone marrow.

Where is adaptive immunity activated?

lymphoid follicle
(mostlyB cells)
medullary
afferent sinus
lymphatic vessel
medullary sinus
artery
vein
T-cell area germinal

Courtesy of Yasodha Natkunam

center
efferent
lymphatic vessel

germinal center
marginal sinus
Geography of an adaptive
Immune response
Geography of an adaptive
Immune response
Geography of an adaptive
Immune response
Regulatory
T Cell

You will hear more about this soon!

Thursday: Big Quiz 1!

After Reading Week!

Lecture 12: Our adaptive immune system

could protect us from a virus from MARS.

Lecture 13: Thymus and T cell development.