BASIC IMMUNOLOGY

Nur Atik
Department of Biomedical Scinces
Faculty of Medicine
Universitas Padjadjaran
 Innate immunity

• Properties of innate immunity

• Components of innate immunity
– Epithelial barriers

– Cellular mechanisms

– Humoral mechanisms

• Role of innate immunity in stimulating adaptive

immune response
 Principle mechanisms of
innate and adaptive immunity
 Mechanisms of innate immunity

- phylogenetically older

- exist before or react immediately after contact with

pathogen
- are not enhanced upon repetead contact with pathogen
(no memory)
- react predominantly to infectious agents
- first line of defense

- stimulate and shape adaptive imunity

Components of innate immunity

- epithelial barriers (skin and mucosal membranes)

- cells (phagocytes, NK cells...)

- humoral components (complement, cytokines etc.)

Functions of epithelia in innate immunty

- physical barrier
Functions of epithelia in innate immunty

- physical barrier

- chemical barrier
(production of antimicrobial peptides)
Functions of epithelia in innate immunty

- physical barrier

- chemical barrier
(production of antimicrobial peptides)

- intraepithelial lymphocytes

- normal bacterial flora

 Cells of innate immunity
Cell type Principal function(s)

Monocytes/Macroph Phagocytosis, inflammation,

ages T-cell activation, tissue repair
Neutrophils Phagocytosis, inflammation

NK cells Killing of infected or tumor

cells
Dendritic cells Phagocytosis, activation of
naive T-cells
Mast cells Inflammation

Eosinophils Defense against parasites

 Role of phagocytes in innate immunity

Order of events in infection

1. Entry of pathogen
 Role of phagocytes in
innate immunity

Order of events in infection

1. Entry of pathogen
2. Recognition of pathogen
(macrophages and dendritic cells)
- molecular patterns and receptors
 Molecular patterns
Common structures for certain groups/classes of pathogens
- essential for their life, replication and/or infectivity
- not present on human cells

Lipoproteins

Flagellin

Examples:

structures of bacterial cell wall (LPS, peptidoglycan, flagellin...)

nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...)

 Role of phagocytes in
innate immunity

Order of events in infection

1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen (macrophages)
- reactive oxygen species (ROS), nitric oxide (NO)
and lysosomal enzymes
 Phagocytosis and
killing of
microbes

Pathogen recognition
Phagocytosis and
killing of
microbes

Zipping of membrane
around microbe
Phagocytosis and
killing of
microbes

Ingestion of microbe
Phagocytosis and
killing of
microbes

Fusion of phagosome
with lysosome
Phagocytosis and
killing of
microbes

Phagocyte activation
 Phagocytosis and
killing of
microbes

Killing of
microbe

http://highered.mcgraw-
hill.com/sites/0072556781/student_view0/chapt
er31/animation_quiz_3.html
 Role of phagocytes in
innate immunity

Order of events in infection

1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Induction of inflammation (macrophages)
- production of pro-inflammatory cytokines
(TNF, IL-1, chemokines...)
Inflammation induction

Proinflammatory cytokines
TNF ― Tumor Necrosis Factor
IL-1 ― Interleukin-1
Chemokines ― Chemotactic cytokines
 Role of phagocytes in
innate immunity
Order of events in infection

1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site
- adhesive molecules (selectins and integrins)
and chemokines
 Leukocytes arrive at the site of infection (extravasation)
http://www.youtube.com/watch?v=WEGGMaRX8f0

http://www.youtube.com/watch?NR=1&v=DMvixApKzKs
Various adhesive
Selectins Integrins molecules

Weak binding
In some inflammatory diseases therapy is directed against
and rolling Activation and
proinflammatory cytokines or adhesive molecules
firm binding Transmigration
(eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis)

Endothelium

TNF & IL-1

Arrival to the site of infection
Macrophages Chemokines
 Role of phagocytes in
innate immunity
Order of events in infection

1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site
6. Pathogen elimination and/or adaptive immunity activation
7. Tissue repair and remodeling (macrophages)
- enzymes and cytokines (growth factors,
metaloproteinases...)
Role of NK cells in innate immunity
NK – Natural killer

Killing of cells infected by

intracellular pathogens
(eg. viruses) and
tumor cells
Role of NK cells in innate immunity
NK – Natural killer

Killing of cells infected by

intracellular pathogens
(eg. viruses) and
tumor cells

Activation of
macrophages (by IFN-γ)
 NK cell killer function

Depends on balance of signals by activating and

inhibitory receptors
 NK cell killer function
Depends on balanse of signals by activating and
inhibitory receptors

NK cell is inhibited

NO KILLING
 NK cell killer function
Depends on balanse of signals by activating and
inhibitory receptors

NK cell is activated
KILLING
 NK cell killer function
Depends on balanse of signals by activating and
inhibitory receptors

- activating receptors recognize stress-derrived structures on cells

(including infected and malignant cells)

- inhibitory receptors recognize MHC class one molecule

Mechanism of NK cell recognition
 NK cell killer function

Apoptosis induction in infected and tumor cells

Killing mechanisms same as in cytotoxic T-cells

- Perforin and granzymes

- FasL and Fas

perforin
NK cell

granzymes
Infected or
tumor cell
apoptosis
FasL Fas
Humoral mechanism of innate immunity

- complement proteins

- cytokines

- other plasma proteins (CRP, MBL etc.)

Cytokines in innate immunity

Inflammation induction
(TNF, IL-1, chemokines...)
 Cytokines in innate immunity

Macrophage and NK cell Inflammation induction

Activation (IL-12 and IFN-γ) (TNF, IL-1, chemokines...)

Antiviral effects (IFN type I, IFN-α and IFN-β)

(eg. INF-α in HCV therapy)

Differentiation of T-cell subpopulation (eg. IL-12)

 Adaptive immunity
• Refers to antigen-specific defense
mechanisms that take several days to
become protective and are designed to
remove a specific antigen. This is the
immunity one develops throughout life.
• There are two major branches of the
adaptive immune responses: humoral
immunity and cell-mediated immunity.
 Strategy of Adaptive Immune
Response
• Overview of humoral immunity
– Mediated by B lymphocytes
• a.k.a B cells
– Develops in bone marrow
– B cells may be triggered to proliferate into plasma
cells
• Plasma cells produce antibodies
– Antibodies produce when antigen bonds B cell receptor
– Some B cells produce memory cells
Strategy of Adaptive Immune
Response
 Strategy of Adaptive Immune
Response

• Overview of cellular immunity

– Mediated by T lymphocytes
• a.k.a T cells
– Matures in thymus
– Divided into 2 subsets
• Cytotoxic T cells
• Helper T cells
– T cell receptors help with antigen recognition
 Anatomy of the Lymphoid
System
• Lymphoid system collection of tissues and
organs designed to bring B and T cells in contact
with antigens
– In order for body to mount appropriate response,
immune cells must encounter antigen
• Lymphoid system includes
– Lymphatic vessels
– Secondary lymphoid organs
– Primary lymphoid organs
Anatomy of the Lymphoid
System
 Anatomy of the Lymphoid
System
• Primary lymphoid organs
– Bone marrow and thymus are primary
lymphoid organs
• Location where stem cells destined to become B
and T cells mature
– B cells mature in bone marrow
– T cells mature in thymus
• Once mature, cells leave primary lymphoid organs
and migrate to secondary lymphoid organs
 Anatomy of the Lymphoid
System
• Secondary lymphoid organs
– Sites where lymphocytes gather to encounter
antigens; organs include
• Lymph nodes
• Spleen
• Tonsils
• Adenoids
• Appendix
– Organs situated strategically
• Allows for initiation of immune response from
nearly any place in body
 Anatomy of the Lymphoid
System

• Lymphatic vessels
– Carry lymph to body tissues
• Lymph formed as result of body’s circulatory
system
– Lymph travels through vessels to lymph
nodes
• Material such as protein is removed
– Fluid portion empties back into blood stream
Antigen Presentation
Initial immune response to any
Ag requires the Ag be
recognized by a T cell.
This is best exemplified by AIDS
w/loss of CD4+ T cells.
Two categories of Ags are
processed and presented to T
Dendritic cell
cells by different mechanisms:
B cell
Exogenous Ags
Endogenous Ags

T cell activated; cytokines released;

Th1, activate M; Th2, activate B cells
 Exogenous antigens
• E. Ag’s (inhaled, ingested, injected), taken up
by APCs:
– Phagocytic cells; dendritic cells, macrophages
– B lymphocytes (produce antibodies)
• APCs
 engulf Ags by endocytosis (endosome-
lysosome)
 Ag degraded into short peptides
 peptides displayed at cell surface nestled w/i
a class II histocompatibility molecule
 recognized by CD4+ T cells
Endogenous Antigens
• Ags that are generated w/i a cell; e.g.,
Mt bug, viral proteins in infected cells

• Peptides displayed at cell surface

nestled w/I a class I histocompatibility
molecule

• Recognized by CD8+ T cells

• CD8+ T cells are cytotoxic

• Have machinery to destroy infected cell

T cell activated; kills infected cell

 Nature of Antibodies
• Structure of the Antibody (Ab)
– Basic Y-shaped structure
– Made of four chains of amino acids held together by disulfide bonds
• Two chains are heavy
• Two chains are light
– Each heavy and light chain has a constant region
• The constant region is known as Fc region
– Each heavy and light chain has a variable region
• Variable region is unique to each Ab
• This region binds to a specific Antigen and is known as “Fab” region
 Nature of
Antibodies
 Protective outcomes of
antibody-antigen binding
› Neutralization
 Prevents toxin from interacting with
cell
› Immobilization and prevention
of adherence
 Antibody bonding to cellular
structures to interfere with function
› Agglutination and precipitation
 Clumping of bacterial cells by
specific antibody
 Bacteria more easily
phagocytized
 Nature of
Antibodies
 Protective outcomes of
antibody-antigen binding
› Opsinization
 Coating of bacteria with antibody to
enhance phagocytosis
› Complement activation
 Antibody bonding triggers classical
pathway
› Antibody-dependent cellular
cytotoxicity
 Multiple antibodies bind a cell which
becomes target for certain cells
 Nature of Antibodies
• Five classes of Ab
– IgM
• First Ab to respond to infection
• 5 – 13% of Ab in circulation
• Structure: pentamer
– Five monomer units joined together at the constant region
• Found on the surface of B lymphocytes as a
monomer
• Only Ab that can be formed by the fetus
 Nature of Antibodies
• Five classes of Ab
– IgG
• Dominant Ab in circulation
– 80 – 85% Ab in circulation
• Structure = monomer
• Only Ab that can cross the placenta
• The antibody of memory!!!!!
– IgA
• Found in secretions
• 10 - 13 % of Ab in circulation
• Structure
– Monomer in serum
– Dimer in secretions
» Breast milk, mucus, tears and saliva
 Nature of Antibodies
• Five classes of Ab
– IgD
• <1% of total Ab in circulation
• Structure = monomer
• Maturation of antibody response
– IgE
• Barely detectable in circulation
• Structure = monomer
• Active in allergic reaction
 Clonal Selection
of Lymphocytes
• When antigen introduces into
body, only appropriate
antibody bonds
– Initiates multiplication of
specific antigen
• Process called clonal selection
• Repeated cycles of cell
division generates population
of copied antibodies
– Termed clonal expansion
• Without sustained
stimulation, cells undergo
apoptosis
Thanks for your attention!

Questions?