Fundamental Immunology

Candida albicans

Talin1

I-hsin Su PhD F-actin

Laboratory of Molecular Immunology
& Cell Signaling
[email protected] By Dr. Thomas Lim 1
 Lecture content:

Innate immunity:
First line of response
Adaptive immunity:
Second line of response
Humoral immune response
B cell, Antibody, Clonal selection
Cell-mediated immune response
T cell, MHC antigen presentation pathways
T cell Clonal expansion
Immune responses against infection
Primary and Secondary immune responses
How do Vaccines Work?
2
 Lecture content:

Innate immunity:
First line of response
Adaptive immunity:
Second line of response
Humoral immune response
B cell, Antibody, Clonal selection
Cell-mediated immune response
T cell, MHC antigen presentation pathways
T cell Clonal expansion
Immune responses against infection
Primary and Secondary immune responses
How do Vaccines Work?
3
What do you know about the role of immune
system?
Defense against invading microbes

Defense against tumor cells or pathogen infected cells

Homeostasis
destruction of abnormal or dead cells
(e.g. dead red or unfit white blood cells, antigen-antibody complex)

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Innate immunity:
First line of response (non-specific )
◼ Relies on already formed components
◼ Rapid response: within minutes of infection
◼ Not specific
 Cellsrespond to a range of pathogens that
have the same group of shared molecules
(LPS, glycan, CpG……etc )
◼ Has no memory (old dogma)
 Trained immunity (new concept)
◼ Does not lead to clonal expansion 5
Innate immunity: mechanisms
◼ Physical barriers / surface secretion
❑Skin, acidic pH in stomach (eliminate most pathogens, but some
microbes still get through such as helicobacter pylori)
❑Mucosal protection (anti-microbial peptides)
◼ Cellular defense mechanisms
❑natural killer cells neutrophils, macrophages,
mast cells, basophils, eosinophils

Basophils &
NK Cell Macrophage Neutrophil Eosinophils
Mast cells
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Innate immune cells in actions

NETosis

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Cytokine production

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 Myeloma B cell line

NK cell

Perforin/granzyme
Releases lytic granules that kill some
virus-infected or tumor cells

rat myeloma
B cell line

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 Lecture content:

Innate immunity:
First line of response
Adaptive immunity:
Second line of response
Humoral immune response
B cell, Antibody, Clonal selection
Cell-mediated immune response
T cell, MHC antigen presentation pathways
T cell Clonal expansion
Immune responses against infection
Primary and Secondary immune responses
How do Vaccines Work?
10
Adaptive immunity: Second line of response (Specific)

❑ Responds slowly, over days

(Relies on genetic events and cellular growth)

➢ Specific
Each cell responds to a single epitope on an antigen

Antigens are usually proteins, peptides and polysaccharides.

Lipids and nucleic acids combined with protein or polysaccharides

➢ Memory
Repeated exposure leads to faster, stronger response

❑ Leads to clonal expansion (discuss later)

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 Adaptive immunity: Mechanisms

◼ Cell-mediated immune response

 T- cells: Helper T cells & Cytotoxic T cells

◼ Humoral immune response

 B- cells: Antibody producing cells → antibodies

Humoral immunity can also be mediated by complement proteins,

and certain antimicrobial peptides

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Non-specific vs. specific immune responses

Pathogens

Pathogens
infected cells

Neutrophil
Innate immune responses Macrophages
NK cells
Adaptive immune responses
Dendritic cells

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 Immune cell lineages
HSC (Bone marrow)

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T cell Immature
precursors B cells

HSC
Hematopoietic Stem Cell

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 Skin

Lymphatic vassal

Macrophage ɸ Dendritic cell

Blood vassal
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 Skin

Lymphatic vassal

Macrophage Dendritic cell

Blood vassal
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 Skin

Lymphatic vassal

Blood vassal
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 Skin

Tissue damages

Lymphatic vassal

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Blood vassal
 Skin

Tissue damages

Lymphatic vassal

Neutrophil

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Blood vassal
 Skin

Tissue damages

Lymphatic vassal

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Blood vassal
 Skin

Lymphatic vassal

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Blood vassal
 Skin

Lymphatic vassal

To Lymph nodes

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Blood vassal
What happens if the initial immune response is not
sufficient to control pathogens at infection site?

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 Immune cell lineages

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Adaptive
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25
Lymph node

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 Lymph node

B cell

BCR

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 Lymph node
T cell receptor (TCR) recognizes peptide antigen presented
on Major Histocompatibility Complexes (MHC)

B cell T cell

BCR
MHCII

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 Lymph node
T cell receptor (TCR) recognizes peptide antigen presented
on Major Histocompatibility Complexes (MHC)

B cell T cell

BCR
MHCII

Kill infected cells

MHCI

CD8
Return to the
T cell infection site
Licensed to kill 29
 Lymph node

B cell T cell

BCR
MHCII

MHCI

CD8

T cell
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 Lymph node

B cell T cell

BCR
MHCII

MHCI

CD8

T cell
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 Lymph node

B cell T cell

BCR
MHCII

MHCI
CD8

T cell
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Clonal selection - B cells

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10 min break
 Lecture content:

Innate immunity:
First line of response
Adaptive immunity:
Second line of response
Humoral immune response
B cell, Antibody, Clonal selection
Cell-mediated immune response
T cell, MHC antigen presentation pathways
T cell Clonal expansion
Immune responses against infection
Primary and Secondary immune responses
How do Vaccines Work?
35
 Antibodies (immunoglobulins)

◼Y-shaped polypeptides
◼ 2 identical heavy chains
◼ 2 identical light chains

◼Five kinds of antibodies (isotypes)

◼ IgG, IgM, IgA, IgD, IgE

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Humoral immune response

or
Infected cell

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 B cell receptor → Antibody

Variable
region

Constant
region

B cells
Antibody producing cells

Plasma cells 38
 Lecture content:

Innate immunity:
First line of response
Adaptive immunity:
Second line of response
Humoral immune response
B cell, Antibody, Clonal selection
Cell-mediated immune response
T cell, MHC antigen presentation pathways
T cell Clonal expansion
Immune responses against infection
Primary and Secondary immune responses
How do Vaccines Work?
39
 Cell-mediated immune response (adaptive immunity)

T-cell
 recognizes peptide antigen on antigen presenting cells (APC) in association
with major histo-compatibility complex class II (MHCII) (CD8+DCs also MHCI)
 recognizes peptides presented on MHCI of cells
 (helps to distinguish self from non-self)

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 T lymphocytes

◼ Helper T- lymphocytes (CD4+)

 CD4+ T cells activate phagocytes to kill microbes
◼ Cytolytic T-lymphocyte (CD8+)
 CD8+ T cells destroy infected cells containing
microbes or microbial proteins

Antigen (peptide)

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 Peptide presentation on MHC

CD8 T cell CD4 T cell

Monitor the internal
environment of cells CD8 T cell
priming

Endoplasmic
reticulum
Clonal expansion – T cells
CD8 T cells

Resident memory cell

Central memory cell

Effector memory cell

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Clonal expansion and polarization
of CD4 T cells

Macrophages Neutrophils B cells

Alternatively activated macrophages
CD8 T cells, NK cells Monocytes
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 Lecture content:

Innate immunity:
First line of response
Adaptive immunity:
Second line of response
Humoral immune response
B cell, Antibody, Clonal selection
Cell-mediated immune response
T cell, MHC antigen presentation pathways
T cell Clonal expansion
Immune responses against infection
Primary and Secondary immune responses
How do Vaccines Work?
45
The immune responses
against infection

Dendritic cells
Primary and Secondary immune responses
Primary response
 Expansion of specific clones of effector cells
and development of memory cells
 Develops in several days

Secondary response
 More pronounced, faster
 More effective at limiting the infection

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 Immunological memory allows the adaptive immune system to
rapidly clear infections that it has encountered before

Some cells become long lasting some times >20 years

“memory” cells

This is mostly due to the higher capacity of memory cells than naïve cells in
responding to the infection.

How does vaccination work?

48
 How does vaccine Work?
◼ Vaccine particles are taken up by dendritic cells
which activate the adaptive immune response

◼ T-cells are activated

◼ Vaccine particles are recognized by B-cells and
activate B cells
◼ Active B cells contribute to T-cell activation
receive T cell help
◼ Activated T cells help B cells
◼ Antibodies are produced

◼ Memory T- and B-cells are formed

◼ Host is prepared to mount immune response

and protect the individual upon NEXT
exposure to pathogen
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 Types of Vaccines
Vaccine What is it? Challenges Examples
Type

Live Weakened version of living microbe Mutation; Measles, mumps, rubella, polio
Attenuated that can’t cause disease Storage (Sabin vaccine), yellow fever, flu

Inactivated or Microbes killed with chemicals, heat Weaker immune Cholera, flu, hepatitis A, Japanese
“killed” or radiation response; encephalitis, plague, polio (Salk
Need boosters vaccine), rabies

Subunit Include antigens (or epitopes) that Identifying specific Hepatitis B, pertussis, pneumonia
best stimulate immune system antigen takes time caused by S. Pneumoniae, HPV

Toxoid Formalin inactivated toxins used as Used when main Diphtheria, Tetanus
vaccine cause of illness is a
bacterial toxin

http://www.niaid.nih.gov/topics/vaccines/documents/undvacc.pdf
http://www.vaccines.gov/more_info/types/ 50
The annual Influenza Vaccines

➢ About Influenza
➢ HA and NA
➢ What is in the Flu Vaccine?

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 About Influenza Virus
Life cycle of influenza virus and targets for therapeutic intervention

Schematic diagram of influenza A virus

Nature Reviews Microbiology 6, 143-155 (February 2008)

Nature Reviews Drug Discovery 6, 967-974 (December 2007)
Hemagglutinin (HA) → Bind target cells
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Neuraminidase (NA) → Release new virus from target cells
 Types of Influenza Virus
◼ Types A and B (related to seasonal epidemics); Type C (mild
symptoms)

◼ Influenza A – subtypes (H#N#)

◼ Based on viral surface proteins
◼ hemagglutinin (H) Types H1-H18
◼ neuraminidase (N) Type N1-N11

◼ Influenza B – no subtypes
◼ Lineages
◼ Yamagata
◼ Victoria

◼ CDC follows internationally accepted naming convention for

influenza viruses
◼ Type/Geog. Origin/strain #/Year isolated (H#N#)
e.g. A/Perth/16/2009 (H3N2) for a virus from human origin

Influenza B/Victoria viruses (70%), followed by H1N1 53

viruses and H3N2 viruses (30%), Jan 2020 http://www.cdc.gov/flu/about/viruses/types.htm
 (198 calculated,131 in nature )

6 month before the flu season → vaccine production

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Schematic of the innate and adaptive immune response during
primary acute viral infection.
The kinetics of the innate and adaptive immune responses in
simple versus severe SARS-CoV-2 infections.
mRNA vaccine against COVID-19
ACE2 receptor

SARS-CoV-2

Lipid nanoparticles (LNPs) Licensed to kill

X DC-priming
Fundamentals of Immunology BS3036/BS3109

Pre-requisite for

Applied Immunology-UAEB BS3331

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