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Immunology Part 1

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Immunology Part 1

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yfgm5ckgjz
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BS4107

Immunology

Dr. Emma Collins (AE5.29)


e.a.collins@uel.ac.uk
Overview
By the end of these lectures you should be able to:
• Be familiar with some of the terminology used in immunology.
• Describe the major components of host defence against infection.
• Compare and contrast innate and adaptive responses.
• Describe the basic functions of selected immune cells
(macrophages, dendritic cells and neutrophils, B and T cells).
• Describe selected innate and adaptive immune effector functions
which protect us from pathogens.
• Describe how the adaptive immune response is used in
vaccination.
What is immunology?
• The study of the molecules, cells, organs and
systems involved in protecting the body from
infections.
• Encompasses topics relevant to dysregulation
of immune responses such as autoimmunity
and autoinflammatory disease.
• Draws on techniques in molecular sciences,
cellular biology, developmental biology
physiology....and more.
Edward Jenner:
The 1st Immunologist

• Observed in the late 18th century that


milk maids who became infected with
cowpox seemed protected from the
usually fatal disease smallpox.

• 1796 he demonstrated that inoculation with cowpox could


protect against smallpox ...called this procedure vaccination.
• However pathogenic microorganisms were not recognized until a
century later by Robert Koch (1884) so Jenner had no idea why
vaccination worked.
How the immune system works
The immune system performs 4 main tasks:

1. IMMUNOLOGICAL RECOGNITION
2. IMMUNE EFFECTOR FUNCTION
3. IMMUNE REGULATION
4. IMMUNOLOGICAL MEMORY
Some terminology
• Leukocytes (nucleated cell found in blood; wbc)
and lymphocytes (cells of adaptive immune
response)

• Antigen and antibodies

• Cytokines and chemokines

• Cluster of differentiation
What is an antigen?
• An antigen is defined as "anything that can be
bound by an antibody“
• Antibodies are proteins produced by adaptive
immune cells that bind specifically to relatively small
parts of foreign molecules known as antigenic
determinants or epitopes.
• Now antigens are considered any substance that can
induce an adaptive/acquired immune response (B or
T-cell).
• Antigens can be short peptides, proteins, sugars,
lipids etc.
Cytokines and chemokines
• Cytokine is a general term to describe various
protein molecules secreted by cells of the immune
system that serve to regulate the immune system.
Can also have effects on other cells in the body.
• Often called interleukins (ILs) i.e. IL-1, IL-2 etc. where
the number stands for the order of their discovery.
Sometimes have other names linked to function
Tumor Necrosis Factor (TNF).
• Chemokines are a sub-type of cytokines with
chemoattractant properties, involved in the
movement and migration of immune cells.
CD#: Cluster of Differentiation
• CD a historical term that was coined to
define cell-surface molecules (generally
proteins) on immune cells that are
T cell
recognized by specific monoclonal
antibodies.
• The cluster of differentiation (CD) then
received a number, for example CD1, CD2
etc., which stands only for the order of granulocyte
their discovery.
• Some CDs expressed on specific cell
lineages
– i.e. CD3 is specific to T cells while others like
CD11 can be found on many lineages. Dendritic cell
Principles of Innate and
Adaptive Immunity
What is innate (natural)
immunity ?
• Physical barriers - skin (dermis) and
mucous membranes.
• Physiological factors - pH,
temperature and oxygen tension limit
microbial growth.
• Protein secretions – lysozyme,
complement, defensins, lactoferrin,
cathelicidin etc.
• Phagocytic cells – macrophages and
polymorphonuclear leucocytes.
Defining characteristic:
• Not specific to individual pathogens.
• No memory persists after encounter.
What is adaptive immunity ?
• The second level of defence.
• Usually increases in strength and effectiveness with
each encounter.
• Component of the foreign agent (antigen) is recognised
in a specific manner and the immune system acquires
memory of it.
• Instructed by 2 types of lymphocytes T cells and B cells.

Defining characteristic:
• Immune response directed at specific pathogen
and memory persists after initial encounter.
At this point the adaptive
receives signals from innate
system to clear infection

Why doesn’t the adaptive immune response work in


the absence of the innate?
What happens with HIV infection and the
adaptive immune response

• HIV+ patient dies of opportunistic pathogen infections NOT HIV virus.

• Severe combined immunodeficiency (SCID) children have no or defective B/T-cells.


Treatment available, bone marrow transplant
Cells and organs
of the immune
system

Which secrete soluble


forms of Antibody
: White blood cells (WBCs)

: monocytes and granulocytes;


precursors of innate cells

Lymphocyte

neutrophil

monocyte
Organs of the immune system

Primary Lymphoid Organs


Where lymphocytes are formed and mature.

• Bone Marrow
• Thymus

Secondary Lymphoid Organs


Monitoring the contents of the extracellular
fluids or mucosal surfaces.

• Spleen
• Lymph Nodes
• MALT/GALT (mucosal/ gut)
Cells and Organs of the immune system
subclavian vein

Immune cells can pass


into blood capillaries
Lymphatic vessel

Subclavian vein

Lymphatic vessel draining into a lymph node.


Innate Immune System
Many intrinsic features make our bodies
hostile to microorganisms!!!

Our body is a fortress that has thick walls and uses chemical warfare to
defend itself.
INNATE IMMUNE CELLS:
Macrophages
• Monocytes are the precursors of macrophages and circulate in the blood.

• One of the first cells that a pathogen is likely to encounter.

• Where: FIXED (resident in particular tissues) or WANDERING


(move through tissues)

• Role: Recognition of pathogen and elimination of pathogens and/or


removal dead/damaged cells by phagocytosis
How are microbes recognized by the Innate Cells?

• There are receptors on the surface


and inside immune cells which can
recognize (bind) a wide variety of
molecules (patterns) from
pathogens. Generic patterns not
specific.

• Called pathogen associated


molecular patterns (PAMPS).

• Each pattern recognition


receptor (PRR) recognizes a
distinct set of pathogen
associated molecules.
Can you name a unique feature found on
bacterial but not mammalian cells?
Immune cell PRR:
TLR: Toll-Like Receptors, a type of
PRR.
TLR2: lipoproteins,
peptidoglycans.
TLR4: LPS and
Lipoteichoic acids

Pathogen PAMPs:
LPS: Lipopolysaccharide
Glucan, mannose and
scavenger receptors: sugars
present on the surfaces of a
large range of microorganisms.

When PRR bind to PAMPs, sequence of events


lead to production of immune mediators….
Cytokines and
other immune
factors. e.g IL-8
attracts
neutrophils
Tissue damage or infections can
trigger inflammatory responses
from innate immune cells Staphylococcus epidermidis

Bacteria trigger Vasodilation and Inflammatory cells


macrophages to release increased vascular migrate into tissue,
cytokines and permeability cause releasing inflammatory
chemokines redness ,heat, and mediators that cause
swelling pain
macrophage

neutrophil
Innate Immune Cells: Neutrophils
• Develop from Myeloid Progenitor in bone
marrow.
• Most numerous cells and important in the
cells in the immune system.
• Where:
• circulate around the body in blood
• activated macrophages and dendritic cells produce
chemokines to rapidly recruit neutrophils into infection sites
• Role: Recognition of pathogen and elimination of pathogens by
phagocytosis.

Neutrophil chasing a bacteria


http://www.youtube.co
m/watch?v=I_xh-bkiv_c
Antimicrobial agents produced by phagocytes –
How do they kill microbes?

What happens inside the phagocyte?..


Microbes are killed inside
phagocytic vesicle
(phagolysosome)

Neutrophils producing O2 radicals to kill bacteria


http://www.youtube.com/watch?v=yicmRt1lQDs
Dendritic cells
Covered with long
membrane extensions
(resembling dendrites of
nerve cells)

• Role: Potent antigen presenting cells


(APC).
• Main function of bone marrow- derived Skin surface
dendritic cells is to activate T - helper
cells. Dendritic
• Characteristics: Found in most cells
tissues.
• Tissue DCs - non-lymphoid tissue
• Intestinal DCs -non-lymphoid sit below
epithelial barrier and ‘catch’ cargo
transported by ‘M’ cells.
• Langerhans cells - reside in skin
• Interdigitating DCs - lymphoid tissue
DCs shuttle antigen from peripheral tissue sites to
lymph nodes where it can be ‘presented’ to T cells
(adaptive immune system)

DCs usually need PRR signals to activate phagocytosis and migration processes.

T cells need to be activated by innate immune cells


Cells and organs of the immune system

Adaptive immune cells

Which secrete soluble


forms of Antibody
Innate immune cells
So far…
• What is immunology and the concept of vaccination (Edward Jenner)
• The main characteristics of the two responses (innate and adaptive)
• Anatomy (Lymph and Lymph nodes)
• Some cells of the innate system and their functions
– Macrophages,
– Neutrophils and
– dendritic cells
• How are microbes recognised by innate immune cells?
– Pathogen Associated Molecular Patterns (PAMPs) (e.g. LPS, peptidoglycan
etc.)
• How do immune cells recognise PAMPs? Macrophages express receptors (PRR)
for many microbe PAMP’s. PRR examples are CD14 (LPS), TLR-2 (peptidoglycan))
• How do immune cells communicate with each other?
– Macrophages and dendritic cells secrete cytokines (IL-6, IL-8, IL-12, TNF-α)
• Effector functions (phagocytosis, and reactive O and N production)
• Which cells bridge the innate – adaptive response? Dendritic cells present
antigens to T cells

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