BASIC IMMUNOLOGY
LECTURE I
INTRODUCTION OF IMMUNE SYSTEM
INNATE IMMUNITY
N. Gachechiladzde
2020 East European University (EEU)
WHAT IS IMMUNITY
Immunity – defense and protection of the body from everything what is unknown, unfamiliar,
unlike and alien from body’s typical, normal environment.
Our body has developed entire system for this
function called immune system - the collection of
cells, tissues and molecules that mediate this
defense.
For body’s defense immune system works through
reaction, called immune response, which
is coordinated action of specific, concrete cells and
molecules
WHAT IMMUNE SYSTEM DOES?
Immune system works against:
Infectious agents
Grafts
Tumor
DEFENSE COULD BE VARIOUS TYPES
Defense mechanisms consist of:
Innate immunity (natural/native)- the initial, simple protection. Normally, this
type of host defense is always present in healthy body. Blocks entry of alien
and/or eliminates ones, that do succeed in entering host tissues. Doesn’t need
much time, doesn’t need special recognition or preparation to act.
Adaptive immunity (specific/acquired) – develops more slowly, needs
stimulation, mediates later, recognizes and adapts to the presence of invaders,
and is more effective
WORK THROUGH DIFFERENT TOOLS
Immunity can be:
Humoral and Cell-mediated
Cell mediated – Lymphocytes, Phagocytes, NK, Dendritic cells, Mast
cells
Humoral – Antibodies, Soluble Secrets, Antimicrobial Enzymes,
Complement System, Cytokines
WHO WORKS FOR US?
HOW FAST THE DEFENSE IS?
INNATE VR ADAPTIVE 1/2
Feature Functional significance
Specificity Ensuring that distinct antigens elicit specific responses
Enabling immune system to respond to a large variety of antigens
Diversity
Leading to enhanced responses to repeated exposures to the same antigens
Memory
Increasing number of antigen-specific lymphocytes to keep pace with microbes
Clonal expansion
Generating responses that are optimal for defense against different types of microbes
Specialization
Allowing immune system to respond to newly encountered antigens
Contraction and
Homeostasis
Non reactivity to self Preventing injury to the host during responses to foreign antigens
cells and tissues
INNATE VR ADAPTIVE 2/2
INNATE IMMUNITY
Innate immunity works against infectious agents, but doesn't react
against non microbial substances (may also be triggered by host cells
that are damaged by microbes, or other sources)
Innate immunity works through
receptors, specialized cells and
humoral factors
Innate immunity can also activate
Adaptive immune response
INNATE IMMUNITY
The components of innate immunity recognize structures that are
shared by various classes of microbes and are not present on host
cells:
Pattern Recognition Receptors (PRR) - for LPS, mannose residues
and other pathogen associated molecular patterns (PAMP)
The innate immune system can also recognize molecules that are
released from stressed or necrotic cells.
Cellular receptors for microbes located on phagocytes, dendritic
cells, lymphocytes, epithelial and endothelial cells – Toll Like
Receptors (TLR)
COMPONENTS OF INNATE IMMUNITY
The innate immune system consists of epithelia, which provide
barriers to infection, cells in the circulation and tissues, and several
plasma proteins.
The three major interfaces between the body and the external
environment are:
the skin protected by continuous
the gastrointestinal tract epithelia that provide
the respiratory tract physical and chemical
barriers against infection
CELLS AND HUMORAL FACTORS OF INNATE
IMMUNITY
Phagocytes Complement
system
Dendritic
cells Cytokines
Natural Acute phase
Killer proteis
Mast cells Other Plasma
Proteins
Other Cells
PHAGOCYTES 1/2
Neutrophils (also called polymorphonuclear leukocytes [PMNs])
normally 4000 to 10,000 per μL in the blood. In response to infections,
the production of neutrophils increases rapidly up to 20,000 per μL
Eosinophils – phagocytic cells with large acidophilic cytoplasmic
granules. They are responsible for combating multicellular parasites.
Neutrophils and macrophages ingest (phagocytose) microbes and
destroy the ingested microbes in intracellular vesicles. They use
several types of receptors to recognize microbes in the blood and
extravascular tissues and to initiate responses that function to destroy
the microbes
PHAGOCYTES 2/2
Monocytes - numbering 500 to 1000 per μL of blood. Blood monocytes
and tissue macrophages are two stages of the same cell lineage, which
often is called the mononuclear phagocyte system.
Macrophages - These large phagocytes are found in essentially all tissues,
where they patrol for potential pathogens. They take various forms (with
various names) throughout the body (e.g., histiocytes, Kupffer
cells, alveolar macrophages and others). Besides phagocytosis, they also
help initiate specific defense mechanisms – adaptive immunity by
recruiting other immune cells such as lymphocytes. They are important
antigen presenting cells. Beyond increasing inflammation and
stimulating the immune system, macrophages also play an
important anti-inflamatory role and can decrease immune reactions
through the release of cytokines.
OTHER CELLS OF INNATE IMMUNITY
Dendritic cells - respond to microbes by producing cytokines that
recruit leukocytes and initiate adaptive immune responses.
Dendritic cells constitute an important bridge between innate and
adaptive immunity
Natural Killer Cells – recognize infected and stressed cells and
respond by killing them. They also activate macrophages. NK are
natural biomonitoring schemes against viral infection and
malignization process
NK T cells, γδ T cells, B1 cells
HUMORAL FACTORS OF INNATE IMMUNITY
COMPLEMENT SYSTEM
Complement system - collection of circulating and
membrane-associated proteins that are important in defense
against microbes. Many complement proteins are
proteolytic enzymes, and complement activation involves
the sequential activation of these enzymes, sometimes called
an enzymatic cascade. The complement cascade may be
activated by any of three pathways:
Alternative pathway
Classical pathway
Lectin pathway
CYTOKINES
HUMORAL FACTORS OF INNATE IMMUNITY
OTHER PLASMA PROTEINS
Plasma mannose-binding lectin (MBL) is a protein that
recognizes microbial carbohydrates and can coat microbes for
phagocytosis or activate the complement cascade by the lectin
pathway.
C-reactive protein (CRP) binds to phosphorylcholine on
microbes and coats the microbes for phagocytosis by
macrophages, which express a receptor for CRP. The circulating
levels of many of these plasma proteins increase rapidly after
infection. This protective response is called the acute phase
response to infection.
INNATE IMMUNITY STIMULATES ADAPTIVE IMMUNE REACTION
Innate Immune response generates molecules and
cytokines, which can function as “signal” for activating
adaptive immune reactions.
Providing the early defense against infections, innate
immune response provides second signals for the activation
of B and T lymphocytes. The requirement for these second
signals ensures that adaptive immunity is elicited by
microbes (the natural inducers of innate immune reactions)
and not by non microbial substances
REFERENCES
Abul K. Abbas, Andrew Lichtman – Basic Immunology (3rd edition)
P. 1-13
P. 18-40
Summary p.21
Summary p. 42
Roit’s Essential Immunology (13th Edition)
P. 4-18
P. 29-46
Summary