25/09/2017

Non Specific and Specific Immunity

Ugbai Teklay

MSc., Biomedical Sciences, FHEA, PGDip

Module Lecturer- EE2511

E-Mail: u.teklay@city.ac.uk
Phone: 02070405731

Non Specific Body Defences

Learning Outcomes

State the role of the skin as the first line of defence in

non specific immunity.

Outline the role of the surface membrane barriers

such as mucous membranes and chemical barriers
e.g. acid pH of Stomach.

Briefly state the function of anti-microbial chemicals

e.g. Complement, Interferon.

Non Specific Body Defences

Learning Outcomes

Briefly explain the process of phagocytosis, giving

examples of cells which undertake this mechanism.

State the function of the Natural killer cells.

Outline the process of inflammation describing the

benefits of this mechanism.

Identify the role of fever and its beneficial effects.

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Immune System
We are constantly being exposed to infectious
agents. Yet, in many ways our immune system
enables us to resist infections.

The immune system refers to a collection of cells

and proteins that function to protect the body from
foreign antigens, such as bacteria, fungi, parasites,
viruses, cancer cells, and toxins.

The immune system has two lines of defence:

innate or non specific immunity and
adaptive or specific immunity.

Non specific Immunity

Non-specific/Innate immunity refers to a wide
variety of body responses to a wide range of
pathogens.

It is the first immunological defence mechanism

against an intruding pathogen.

It is natural and present before infection.

Response is antigen-independent.

Non specific Immunity

It is a rapid immune response, occurring within
minutes or hours after aggression.

Exposure results in no immunologic memory.

The elements of the innate immune system

includes physical barriers, physiologic,
phagocytic, and inflammatory barriers.

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Non-specific host-defence mechanisms for

barriers of innate immunity
Barrier Mechanism

Anatomic

Mechanical barrier retards entry of

microbes
Acidic environment (pH 3-5)
Skin retards growth of microbes
Normal flora compete with microbes
for attachment sites

Mucous entraps foreign microbes

Mucous membrane
Cilia propel microbes out of body

Non-specific host-defence mechanisms for

barriers of innate immunity

Barrier Mechanism
Physiologic

Body temperature/fever response

Temperature
inhibits growth of some pathogens
Acidic pH of stomach kills most
Low pH
undigested microbes
Lysozyme cleaves bacterial cell wall
Interferon induces antiviral defenses in
Chemical mediators uninfected cells
Complement lyses microbes or
facilitates phagocytosis

Non-specific host-defence mechanisms for

barriers of innate immunity
Barrier Mechanism

Various cells internalize (endocytosis) and

break down foreign macromolecules
Phagocytic barriers
Neutrophils and tissue macrophages
phagocytose, kill and digest whole organisms

Tissue damage and infection induce leakage

of vascular fluid containing serum protein with
Inflammatory barriers
antibacterial activity, leading to influx of
phagocytic cells into the affected area

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Antimicrobial proteins to infection

When there is damage to tissues the anatomical
barriers are breached and infection may occur
and this causes inflammation. Humoral factors
found in serum play an important role in
inflammation.

Complement is a group of over 20 proteins that

make up about 10% of the globulin part of
serum.

Complement components promote phagocytosis

by identifying and coating foreign antigens;
cause cytolysis of microbes and contribute to
inflammation.

The Complement System

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Antimicrobial proteins to infection

Lysozyme, in serum and tears, breaks down the
bacterial cell wall.

Interferons are antiviral proteins that are

produced from viral infected cells.

Interferons protect uninfected host cells from

viral infection and also play a role in the
activation of immune cells such as macrophages
and natural killer cells.

Interferon
Interferon (IFN)

IFN
Macrophage
Infected cell IFN (phagocytizes
IFN infected cell)
Perforin
Granzymes
Normal cell
NK cell
(causes
apoptosis)
Synthesizes enzymes that Apoptosis
interfere with viral replication

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Cellular barriers to infection

Numerous cells are involved in the innate
immune response such as phagocytes, mast
cells, basophils, eosinophils and natural killer
cells.
Neutrophils: migrate to infected area and are the
most important cellular components in bacterial
destruction.
Neutrophils contain granules that, when
released, assist in the elimination of pathogenic
microbes- they phagocytose and kill the bacteria
intracellularly.

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Innate Immunity Cells

Natural Killer Cells

Neutrophils & Macrophages

Eosinophils

Basophils & Mast Cells

Macrophages: Large phagocytic cells that can

ingest more and larger particles than neutrophils.

Active in the late stages of infection, including the

clean up of dead neutrophils and other cell debris.

Unlike neutrophils (which are short-lived cells),

macrophages are long-lived cells that not only
play a role in phagocytosis, but are also involved
in antigen presentation to T cells.

Macrophages are required for the induction of

specific immune responses.

Neutrophil and macrophage: Phagocytic cells

Infectious agent Macrophage

engulfed Lysosome
Phagosome

Phagolysosome
destroys infectious
agent

Residue is exocytosed

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Neutrophil Macrophage (Big eater)

The Foot soldier The Clean-up Crew
Most common leucocyte. Arrive later after the initial
1st to arrive in response to response.
infection. Stay longer afterwards.

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Natural Killer (NK) cells

NK cells (large granular lymphocytes) play a
major role in the destruction of virus infected
cells and tumour cells.

Destruction of infected cells is achieved through

the release of perforins and granzymes from NK-
cell granules which induce apoptosis-
programmed cell death.

NK cell: Apoptosis-initiating cells

Perforin and
granzyme

Perforin forms a
transmembrane pore
Granzymes enter
pore, causing
NK cell apoptosis of cell

Unhealthy or
unwanted cell

Apoptosis

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NK cells: Police on patrol. Cells on the kill list:

Stored in lymph vessels Virus- & Bacteria-infected cells
But naturally circulate in blood. Tumor cells
Immune surveillance. Transplanted tissue / organs

Mast cells- non motile cells in connective tissue,

especially near capillaries.

Located at potential points of entry of micro-

organisms into the body, such as the skin, lungs,
gastrointestinal tract and urogenital tract.

Basophils = motile WBCs that can leave the

blood and enter infected tissues.

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Basophil and mast cell: Proinflammatory chemical-secreting cells

Arteriole
Vasodilation
Basophil

Histamine
Increases capillary
permeability Capillary

Heparin
Anticoagulant
Eicosanoids
Increases inflamation Venule

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Basophils: Traffic control Vasodilation, Anticoagulation &

Found in blood stream. Permeability: opens up route for
Mast cells: in connective tissue, other immune cells, and leads to
mucosa & internal organs. inflammation

Eosinophils: Parasite-destroying cells

Cytotoxic chemicals
Parasitic worm

Eosinophil

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Eosinophils: The Heavy Artillery Eosinophils Actions

Release degrading enzymes & Targeting multicellular
cytotoxins. organisms.
Create transmembrane pore to Response associated with
inject toxic mixture into target. allergies & asthma.
Phagocytosis of antigens.

Inflammation
Inflammation is a defensive response to
infection, and tissue injury.

Inflammation is a non-specific attempt to dispose

of microbes and foreign materials, dilute toxins,
and prepare for healing.

The physiological purpose of inflammation is -

host defense against infection & tissue repair
response.

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The classic signs of inflammation are:

Redness (rubor),

Pain (dolor),

Heat (calor),

Swelling (tumour) and

Sometimes-Loss of
function (Laesio Functi)

Beneficial effects of inflammation

Damaging effects of inflammation

The pathological consequences of
inflammation are:

Release of enzymes digestion of normal

tissues

Swelling in an enclosed space can be

damaging- tumour growth, inappropriate
inflammatory response e.g.: asthma,
autoimmunity, sepsis and fibrosis.

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Acute & Chronic Inflammation

Acute Inflammation
Rapid onset
Usually resolves
Increased neutrophil numbers

Chronic Inflammation
Usually follows an acute episode
Insidious onset prolonged course
Increased lymphocyte and macrophage
numbers.

Fever
Fever/pyrexia, is when body temperature rises
above 37oC in response to pyrogens.

Benefits of fever: Intensifies effects of interferons,

inhibits growth of some microbes, increases tissue
permeability, speeds up body reactions that aid
tissue repair and accelerates adaptive immunity.

Risks of high fever: changes metabolic pathways,

denatures enzymes, Seizures (>38.9oC), irreversible
brain damage (>41.1oC)and death (>42.8oC)

Specific Body Defences

Learning Outcomes

State the requirements of an acquired specific

defence mechanism.

Define the terms antigen and antibody.

Describe the role of B Lymphocytes in Humoral

immunity.

Name the classes of Immunoglobulins and briefly

state their roles.

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Specific Body Defences

Learning Outcomes
Outline how antibodies act against antigens.

Describe the role of the T Lymphocytes in Cell

Mediated immunity.

Briefly explain the differences between primary and

secondary immune responses and distinguish
between active and passive immunity.

Specific Immunity
Specific/Adaptive immunity acts as a second line of
defence and response is antigen-dependent

Offers no immediate protection to a foreign antigen.

has slow response to a first encounter to antigens, takes

several days. It is antigen-specific.

Exposure results in immunologic memory, which enables

the host to mount a more rapid and efficient immune
response upon subsequent exposure of the same
antigen.

Specific Immunity
Immunity that results from activities of lymphocytes.

There are two types of adaptive immunity:

antibodymediated immunity and cellmediated
immunity.

B lymphocytes provide antibody mediated

immunity/Humoral immunity.

T lymphocytes provide cell mediated immunity.

The lymphocytes are often ineffective for several

days but both B&T cells produce memory cells which
trigger more rapid subsequent immune responses.

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Antibody-mediated Immune Response

B cells develop into plasma cells which produce
antibodies/immunoglobulins in the presence of
specific antigen.

Antibody fit like a key into specific shape of

antigen which act like a lock.

Effective against extracellular pathogens

General Functions of Immunoglobulins (Ig)

Igs are glycoprotein molecules that are produced

by plasma cells in response to specific antigens.

Actions of Igs/antibodies include neutralization of

antigen, immobilization of bacteria, agglutination
of antigen and activation of complement.

Antigens

Antigens (Ags) are chemical substances that are

recognized as foreign by the immune system.

Foreign antigens are produced outside the body

and are capable of provoking immune responses.

Based on chemistry and structure, antibodies are

grouped into five principal classes (IgG, IgA, IgM,
IgD, and IgE), each with specific biological roles

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Immunoglobulin (Ig) Classes

IgG
The major Ig in serum - 75%.

The only class of Ig that crosses the placenta.

Fixes complement .

Neutralizations of toxins and viruses.

IgA

2nd most common serum Ig.

Major class of Ig in secretions - tears, saliva,

mucus.

Important in local (mucousal) immunity from

toxins, viruses and bacteria.

Does not fix complement, unless aggregated.

IgM
Third most common serum Ig.

First Ig to be made by the foetus and the first Ig

to be made by a virgin B cells when it is
stimulated by antigen

As a consequence of its pentameric structure,

IgM is a good complement fixing Ig.

Very efficient in leading to

the lysis of microorganisms.

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IgD

Found in low levels in serum.

Its role in serum uncertain- may be involved in

cell homeostasis.

Found on B cell surfaces where it functions as

a receptor for antigen.

Does not bind complement.

IgE

The least common serum Ig.

IgE binds very tightly to Fc receptors on

basophils and mast cells even before interacting
with antigen, hence, IgE binding involve in
allergic reactions.

Helps in killing parasites.

IgE does not fix complement.

Cell-mediated Responses
A cellmediated immune response begins with
activation of a small number of T cells by a
specific antigen.

Cell-mediated responses are effective against

intracellular pathogens

T cells play a regulatory role both in antibody-

mediated responses and cell-mediated
responses.

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Cell-mediated Responses

The T Lymphocytes can be divided in to two

classes.

the helper T cells (TH cells)- which are the

regulatory cells and

the cytotoxic lymphocytes (TC cells)-destroy viral

infected cells.

Cell-mediated Responses

TH cells secrete cytokines which acts as a

costimulator for cytotoxic T cells and B cells.

Then B cells become activated & secrete

antibodies in response to antigenic challenge.

Activated TC cells eliminate microbes by

releasing granzymes and perforins.

TH cells also stimulate the nonspecific immune

response.

Immune Responses
Primary response- immune response that occurs as a
result of the first exposure to an antigen.

Secondary(memory) response- immune response that

occurs when the immune system is exposed to an
antigen against which it has already produced a primary
response.

Immunization- process by which a subject is rendered

immune by deliberately introducing an antigen or
antibody into the subject.

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Acquired Immunity

Immunopathology
There is a great deal of synergy between the
adaptive immune system and its innate counterpart.

Defects in either the innate or adaptive immune

response can provoke illness or disease.

These disorders are generally caused by:

A. an overactive immune response known as
hypersensitivity reactions,
B. an inappropriate reaction to self known as
autoimmunity or
C. ineffective immune responses known as
immunodeficiency.

References
Turvey and Broide(2010). Chapter 2: Innate Immunity. J Allergy Clin
Immunol. 125:s24-s32.

Playfair J & Bancroft G (2008) Infection and Immunity, 3rd edition, Oxford
University Press, Oxford.
McKinley, M. P., O'Loughlin, V. D., & Bidle, T. S. (2013). Anatomy &
physiology: An integrative approach. New York, N.Y: McGraw-Hill. [eBook]:
Figure 22.7a: Innate Immunity
Figure 22.3: Cells of Innate Immunity
Figure 22.4: Effects of Interferon
Figure 22.5: The Complement System
Infected Ingrown Toenail. From Wikimedia Commons. Author: Menetekel
(2007).
Basophil. From Wikimedia Commons. Author: BruceBlaus (2013).
Activated Eosinophils in Idiopathic Hypereosinophilic Syndrome. From
Wikimedia Commons. Author: NIAID (2013)
Natural Killer Cell. From Kidney Cancer Chronicles Website.
[http://kidneycancerchronicles.com/of-porn-and-natural-killer-cells-the-
mean-streets-of-the-national-institutes-of-health]

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