Immunology

Chapter 1: An Overview of the

Immune System
1.1 Definition of terms
Immunology

The study of immune system or immunity

the study of all aspects of host defense against infection and of

adverse consequences of immune responses.

The study of the physiological mechanisms which enable the body

to recognize materials as foreign and to neutralize, metabolize or
eliminate them without injury to the host tissue.
Immunity
State of protection from infectious diseases
1.1 Definition of terms
Immune system

A remarkably versatile defense system that has evolved

to protect animals from invading pathogenic
microorganisms and cancer.

It is able to generate an enormous variety of cells and

molecules capable of specifically recognizing and
eliminating an apparently limitless variety of foreign
invaders.
 The immune system

Immune
System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Cell- Humoral

Components Components Mediated (Ab)
The immune system
Overview of the Immune System
The Innate immunity
Natural immune system (Innate Immunity)
 Non – specific
 First line of defense
 Repeated exposure - no augmentation
• Components
Biochemical
Physical
Cells
1.4 Innate Immunity

1. Components Lysozymes
a. Biochemical
• enzymes, C’, etc.
Mucus
• secretions Cilia: trachea
• pH
b. Physical Sebaceous glands
• skin Skin
• cilia
c. Cells Acid in
• Phagocytes, NK stomach
2. Example Commensal
a. Burn response organisms in
gut & vagina

Spermine in semen
1.4 Innate Immunity
Skin and Mucosal Surfaces -
Physical Barriers Against Infection
• Skin is first line of defense against infection
• Tough impenetrable barrier
• Skin continuous with epithelia lining
• respiratory
• gastrointestinal
• urogenital tracts

The impermeable skin gives way

to specialized tissues that are
more vulnerable to microbe attack;
Known as mucosal surfaces or mucosae
Skin and Mucosal Surfaces -
Physical Barriers Against
Infection
• Mucosal surfaces are bathed in mucus; thick fluid containing

glycoproteins, proteoglycans, and enzymes - protective

• Lysozyme in tears and saliva – antibacterial

• Respiratory tract mucus is continuously removed to clear

unwanted material

• Stomach, vagina, skin acidic – protective

When skin and mucosal barriers are breached -

immune system responds
External Innate Defense Systems
• Prevent entrance:
• Structural barriers – effective with most microorganisms
• Skin - epidermis = layers of tightly packed epithelial cells. Outer
layer is dead cells and keratin, waterproofing protein
• Inner layer skin - dermis = blood vessels, hair follicles, sweat
glands, and sebaceous glands that produce an oily secretion
called sebum
• Cilia and cough reflex – helps expel microbe containing mucous

• Sneeze
1.4.1 External Innate Defense Systems
• Mucus - conjunctivae, alimentary, respiratory, and
urogenital tracts
• saliva, tears, and mucous secretions wash away invaders and
contain antibacterial or antiviral substances.
• acidity (pH 5.6) of sweat, sebaceous glands, vagina (pH 5) and
stomach (pH 1) – unfriendly to many microorganisms
• enzymes present in the skin and stomach, tears

• Normal flora - out compete pathogens for attachment sites

on the epithelial cell surface and for necessary nutrients.
1.4 Innate Immunity
Physiologic Barriers
• Soluble factors contribute to innate immunity, they are
collectively known as acute phase reactants.
• Normal serum components, non-specific responders to
inflammation
• Increase because of infection, injury, trauma
• Produced mostly by liver in response to inflammation
and cytokine stimulation
• Cytokines: IL-1, IL-6 and TNF alpha which are produced by
macrophages and monocytes at inflammatory site are
activators
1.4 Innate Immunity
• Complement – a series of enzymes normally circulating in an
inactive form
• May be activated by the classical or alternate pathways

• Can result in lysis or enhanced phagocytosis of cells

 Introduction to Complement
• Complement component are proteins and glycoproteins,
about 5% of serum proteins
• Synthesized mainly by liver hepatocytes, monocytes, tissue
macrophages, plus epithelial cells of GIT & GUT.

• Complement components are designated by

• numerals (C1–C9),
• letter symbols (e.g., factor D), or

• Peptide fragments formed by activation of a component are

denoted by small letters.
 Introduction to Complement
• Are normally present in the circulation in an inactive
state – once activated show enzymatic action on
subsequent components and finally target antigen

• The two major pathways of complement activation are

• the classical pathway which is activated by antigen antibody
complex
• and the alternative pathway which is activated on microbial
cell surfaces in the absence of antibody.
Complement
• Complement was discovered as a component of normal plasma
that augments killing of bacteria by antibodies
• Complement can be also be activated early in infection in the
absence of antibodies
Complement summary
The Complement System
• Serum proteins of the complement system are activated
in the presence of a pathogen, forming a bond between
complement protein and the pathogen

• The attached piece of complement marks the pathogen

as dangerous

• The soluble complement fragment attracts a phagocytic

white blood cell to the site of complement activation
The Complement System
• The effector cell (macrophage) has a surface
receptor that binds to the complement fragment
attached to the pathogen

• The receptor and its bound ligand are taken up

into the cell by endocytosis, which delivers the
pathogen to an intracellular vesicle called a
phagosome, where it is destroyed
The Complement System
1.4 Innate Immunity
• Lysozyme, a hydrolytic enzyme in mucous
secretions and in tears, can cleave the
peptidoglycan layer of bacterial cell wall.

• Interferon, proteins produced by virus-infected

cells.
• Has many functions including ability to bind to nearby
cells and induce a generalized antiviral state.
1.4 Innate Immunity
C-Reactive Protein

• Normally trace levels in serum

• Early acute inflammation indicator:

• increases within 4-6 hrs of infection or trauma

• 100 to 1000 fold increase serum concentration

• concentration drops rapidly in serum when stimulus removed

• Enhances opsonization, agglutination, precipitation, and

classical pathway complement activation – enhances removal
of irritant
1.4 Innate Immunity
Phagocytosis

• Phagocytic cells Chemotaxins such as

• Complement components
• Coagulation cascade proteins
• Bacterial and viral products

• Attract phagocytic cells including:

• Mast cell, lymphocyte, macrophage, neutrophil products
1.4 Innate Immunity
Phagocytosis

• Physical contact between phagocytic cell and

foreign object results in
• Formation of phagosome
• Formation of phagolysosome
• Digestion
• Release of debris
1.4 Innate Immunity
• Phagocytosis ...
• Adherence – binding of organism to the surface of
phagocytic cell.
• Engulfment:- is the ingestion of m/o’s and formation of
phagosomes.
• Digestion – after the foreign particle or m/o’s is ingested,
cytoplasm lysosome fuse with phagosome The enzymes
of lysosome then contribute to microbial killing and lysis.
Phagocytosis/Endocytosis
• If a microorganism crosses an epithelial barrier and begins to replicate,
it is recognized by phagocytes- macrophages and neutrophils

• Phagocytes can distinguish surface molecules on microorganims from

surface molecules on host cells – called pattern recognition

• Ingestion of microorganisms is called phagocytosis

• A cell’s membrane expands around particles to forms vesicles called

phagosomes

• Upon phagocytosis, phagocytes produce toxic products that kill

microorganisms, which include nitric oxide, superoxide anion and
hydrogen peroxide
 Phagocytes- Neutrophils- PMN
• The most abundant mobile phagocyte (eating cell)
is the neutrophil (polymorphonuclear cell, PMN)
• Phagocytosis is coupled to release of cytokines and
other inflammatory mediators
• Cytokines recruit neutrophils and other immune cells
• Granular leukocytes comprise the majority of white blood
cells
• Patrol the blood stream in search of invading microbes
• Neutrophils are specialized killing machines, short-
lived, when they die they produce pus
• Eventually mopped up by macrophages
Neutrophils are Mobilized from the Bone
Marrow, and Target (home) to Infection Sites
 Mononuclear Phagocyte System
• Mononuclear phagocyte system
• System of phagocytes located mainly in the organs and
tissues
• Monocytes are present in the blood stream and settle
in the tissues as macrophages

• Macrophage-like cells in the liver – Kupffer cells

• Macrophage-like cells in the brain – Microglia

1.4 Innate Immunity Phagocytosis ...
Natural Killer Cells
• NK cells (large granular lymphocytes) are found
throughout the tissues of the body but mainly in the
circulation

• Constitute 5-10% of lymphocytes in human blood

• Contain cytotoxic substances which are important for

protection against viruses and some tumors

• Secrete cytokines which prevent viral replication and

helps to activate T cell mediated immunity
Figure 1-9 part 2 of 6
Figure 1-9 part 5 of 6
Figure 1-9 part 4 of 6
Figure 1-9 part 6 of 6
Inflammatory Responses
• When the outer barriers of innate immunity—skin
and other epithelial layers—are damaged,
• the resulting innate responses to infection or tissue
injury can induce a complex cascade of events known
as the inflammatory response.
Inflammatory Responses
• Inflammation may be
• acute (short-term effects contributing to combating
infection, followed by healing)—for example, in
response to local tissue damage
• or chronic (long term, not resolved), contributing to
conditions such as arthritis, inflammatory bowel
disease, cardiovascular disease, and Type 2 diabetes
Inflammatory Responses
• The hallmarks of a localized inflammatory response
• redness and swelling with heat and pain
• an increase in vascular diameter (vasodilation), resulting in
a rise of blood volume in the area.
• Higher blood volume heats the tissue and causes it to
redden.
• Vascular permeability also increases, leading to leakage of
fluid from the blood vessels, resulting in an accumulation
of fluid (edema) that swells the tissue
Inflammatory Responses
• These hallmark features of inflammatory responses
reflect
• the activation of resident tissue cells—macrophages, mast
cells, and dendritic cells to release chemokines, cytokines, and
other soluble mediators into the vicinity of the infection or
wound.

• Recruited leukocytes are activated to phagocytose

bacteria and debris and to amplify the response by
producing additional mediators
Inflammatory Responses
• Resolution of this acute inflammatory response includes
• the clearance of invading pathogens, dead cells, and damaged tissue

• the activation of the systemic acute phase response including the

initiation of wound healing
• and the induction of adaptive immune responses.

• However, if the infection or tissue damage is not resolved, it

can lead to a chronic inflammatory state that can cause more
local tissue damage and potentially have systemic
consequences for the affected individual.
• Figure. Initiation of a local inflammatory response.
 1.5. The immune system

Immune
System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Cell- Humoral

Components Components Mediated (Ab)
1.5. The immune system
Overview of the Immune System
1.5 Adaptive Immunity
 Specific
 Second line of defense
 Repeated exposure - augmented – memory
 Faster response, More vigorous response
 Longer lasting response

Components
Classic Immune System
 Cells (Cell mediated) =CMI
 Soluble Factors (Humoral immunity) = HI
1.5 Adaptive immune system
• Capable of recognizing and selectively eliminating specific foreign
microorganisms and molecules(i.e., foreign antigens).

• Different populations of lymphocytes and their products are the

major actors together with accessory cells
• Antigen presenting cells (APCs)

• Cardinal features are :

• Specificity

• Diversity

• Memory
1.5 Adaptive immune system
Cardinal Features of adaptive Immune Responses
• Specificity –

• specific for distinct antigen

• for different structural components of a single complex protein,
polysaccharide, or other macromolecules.

• Portions of such antigens recognized by individual lymphocytes

are called determinants or epitopes.

• This fine specificity exists because individual lymphocyte

express membrane receptors able to distinguish subtle (slight)
differences in structure between distinct antigens.
1.5 Adaptive immune system
• Diversity- total number of antigenic specificities
of the lymphocytes in an individual, called the
lymphocyte repertoire, is extremely large.
• estimated mammalian immune system can
discriminate 109 to 1011 distinct antigen
• It is the result of variability in the structures of
antigen- binding sites of lymphocyte receptors for
antigens.
1.5 Adaptive immune system
• Memory- Exposure of the immune system to
foreign antigen:
• enhances its ability to respond again to that antigen.
• Responses to second and subsequent exposure to the
same antigen, called secondary immune responses
• are usually more rapid and larger than the first or
primary immune response.
Adaptive immune continued
• An effective immune response involves three major
groups of cells:
• Cellular Immunity (T lymphocytes), Humoral Immunity (B cells),
and Accessory cells (antigen-presenting cells).

• The two major populations of lymphocytes—B

lymphocytes (B cells) of Humoral immunity and T
lymphocytes (T cells) of Cellular Immunity provide us
with our specific adaptive immunity
Summary of innate and adaptive immunity
Comparison of Innate and Adaptive Immunity

Innate Immunity Adaptive Immunity

• No time lag • A lag period

• Not antigen specific • Antigen specific

• No memory • Development
of memory
Adaptive and Innate - Interactions
Infectious Innate Immunity No
Exposure holds Disease

Innate Immunity
Fails
Adaptive Immunity
Specific memory

Disease

Adaptive Second Infectious

Recovery Exposure
Immune system
Same organism