CLINICAL IMMUNOLOGY

1. HOST PARASITE RELATIONSHIP

2. Introduction to Immunology

Fourth year Pharmacy Students

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1. HOST-PARASITE RELATIONSHIPS

Triangle of relationships
MICROBES

HUMANS DRUGS
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 Outcome of the Relationship
between the host and the Microbe

1. Colonization without harm

2. Subclinical (Silent) infection
3. Infection (severity depends on the
host and the microbial factors)

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 Sources of Infection
1. Endogenous
q Bacteria normally present in the body and cause
disease under certain conditions e.g. E. coli
2. Exogenous: From outside of the body
1. Human (case or carrier)
ü Incubatory carrier
ü Convalescent carrier
ü Mechanical carrier
ü Chronic carrier
ü Subclinical carrier
2. Animals e.g. Bovine TB
3. Arthropods e.g. Malaria
4. Dust e.g. Tetanus
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 Communicability of disease
• Communicability: infectious disease can be
transmitted either directly (e.g. person to
person) or indirectly (e.g. contaminated water).

• Factors involved in the communicability of an

infectious agent include:
1. Source, including dormant or latent infections
(carriers).
2. Number of infectious agents released from a host.
3. Capability of surviving transit from host to host.
4. Percentage of the host population that is
susceptible to the agent.

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 Methods of Infection
1. Food and water e.g. Cholera, enteric fever
2. Inhalation e.g. TB
3. Contact e.g. Tinea
4. Wounds e.g Tetanus
5. Injection e.g. HIV and HBV
6. Sexual (mucous membranes) e.g Syphilis
and gonorrhea
7. Arthropodes
8. Idiopathic

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Pathogenicity Classification of Bacteria

1. Pathogenic Bacteria
1. Virulent: invade, penetrate and multiply
causing disease
2. Attenuated: can not cause disease
2. Non pathogenic bacteria (commensals)
§ Normally present in the body and cause
disease only under certain conditions
(opportunistic pathogens) e.g. E.coli in
GIT® No disease and in UT® UTI

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MECHANISMS OF PATHOGENESIS
(Factors related to the Microorganism)
• Pathogenic properties of bacteria:
microorganisms cause disease by two basic
mechanisms:
1) invasion of tissue and
2) production of toxins.
1. Invasiveness: the ability to invade host
tissues.
– Intracellular pathogens vs extracellular pathogens:
Intracellular pathogens generally produce chronic
disease, extracellular pathogens generally produce
acute disease (e.g. Mycobacterium tuberculosis vs
Streptococcus pyogenes). 8
 Invasiveness (cont.)
• Capsules: Some bacteria produce hydrophilic gels
that inhibit phagocytosis (e.g. smooth vs rough
strains of Streptococcus pneumoniae).
• Adaptation: microenvironments of the host body
provide habitats for bacteria that are capable of
selective tissue invasion (e.g. Neisseria
meningitidis vs Streptococcus pneumoniae . Both
inhabit the human nasopharynx, but only the
latter invades the lower respiratory tract).
• Extracellular enzymes: Some bacteria produce
enzymes like hyaluronidase or collagenase that
degrade host tissues. 9
 2-Toxigenicity
i.e. the production of toxins.
1. Exotoxins: secreted proteins that are generally very
toxic but heat labile. They are usually very good
immunogens.
• Exotoxins are found mostly in Gram-positive
organisms.

2. Endotoxins: complex polysaccharides (LPS) that are a

part of the bacterial cell wall. they are usually poorly
immunogenic.
• These toxins are released when cells lyse, are
generally heat stable, and found mostly in Gram-
negative bacteria. 10
 3-Virulence
• The combination of invasiveness and toxigenicity
producing the ability to overcome host defenses.
1. Measurement of virulence: LD50 (% dead vs dose).

2. Variability in virulence potential may be genotypic (e.g

smooth vs rough strains of Streptococcus
pneumoniae , lysogeny in Corynebacterium
diphtheriae ) or phenotypic (e.g. the production of
capsular polysaccharides in the presence of rich
carbohydrates).

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 HOST Factors and DEFENSES
• Host defenses include both physiologic barriers and
immunological responses.
• Some defenses are non-specific, others are highly
specific.
• Host defenses can vary considerably due to many factors
including alcohol, drugs, nutrition, immunologic disorders,
etc.
Skin and mucous membranes provide the first line of
defense through:
1. Mechanical factors: physical barrier to penetration.
2. Chemical factors: gastric acidity, unsaturated fatty
acids, lysozyme.
3. Microbial factors: antagonism by normal flora.
4. Immune responses
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2. INTRODUCTION
TO IMMUNOLOGY

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 General Immunology

The immune system is composed of:

• many interdependent cell types,
• organs and
• tissues
that jointly protect the body from
infections (bacterial, parasitic, fungal,
or viral) and from the growth of tumor
cells.
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Mid-late 1800s
Robert Koch showed that microorganism cause
infectious diseases and that different organisms
cause different diseases
Louis Pasteur first show how vaccines could be
made to a variety of bacterial pathogens.
Nowadays, 4 broad categories of pathogens (disease
causing organisms): viruses, bacteria, fungi, and
“parasites” (eukaryotes including protozoans and worms)
Emil Von Behring and Shibasaburo Kitasato found,
in the serum of immune individuals, a that substance
bound to the bacteria to which they were immune.
Called the substance ANTIBODY 15
In 1796 Edward Jenner infects a boy with cow pox to
protect against small pox (before germ theory of disease) 16
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Immune Responses

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 Specific Immune Responses

Humoral Immunity Cell-mediated Immunity

(Antibody) (Cytotoxicity)
Mechanisms of protection against infection and disease are
diverse. Primarily they can be divided into two major
categories:

1. INNATE (NON-SPECIFIC) IMMUNITY.

This consists of the pre-existing defenses of an animal such as
barrier layers (skin etc) and secretions
2. Specific or adaptive immunity
This is a response to a specific immune stimulus (antigen) that
involves cells of the immune system and frequently leads to a
state of immune memory.
• In adaptive immunity, which occurs after a lag period during
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which immune B and T cells become activated, invading
 Why adaptive immunity?

• Shortcomings of innate immunity:

– Non-specific
• Similar pattern of response for all pathogens
– Poor regulation
• Control mechanisms are poor or lacking
– Poor amplification
• Response magnitude same for all insults
– Lack of self discrimination
• Harm to self results for lack of specificity
– Short duration
– No memory
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The enemies are different…..

BACTERIA -
Clostridium difficile FUNGUS -
(causes antibiotic- Epidermophyton
associated floccosum
colitis & diarrhea) (causes athlete’s foot)

VIRUS- Polio

PARASITE -
Tapeworm
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 ….therefore the responses
must be tailored to specific
enemies.
• Successful immune response is a huge
investment!! You need a way to remake
it:
• Faster
• Larger
• More specific
• Less damage to self
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• Innate immunity is the immunity that is immediately
available without having to adapt to the specific
pathogen that is present.
• It is not specific to a particular organism such that
identical responses can protect against several
organisms.
• Innate immunity is germline encoded (evolved on an
evolutionary time scale).
• Innate immunity is mediated by phagocytes (cell
that ingest bacteria or other particulate matter)
such as macrophages and neutrophils.
• It is also mediated by chemical compounds that
will be described later. 23
Adaptive Immunity:
• Specific Immune Response (e.g., antibody) against a
particular microorganism is an adaptive immune response.
• That is, it occurs during one’s lifetime as an adaptation to
the presence of that particular organism.
• An adaptive immune response might provide lifelong
protective immunity to a given pathogen.
• These are central principles of adaptive immunity

• Specific immunity can be induced by a variety of substances.

Things that induce adaptive immunity are called ANTIGENS

Antigen-specific responses are mediated by lymphocytes

• Together, innate and adaptive immunity prevent
most infectious diseases (no symptoms from
exposure to the microorganisms) or cure infections

• We mostly will deal with adaptive immunity.

• However, you must understand innate immunity

and how adaptive immunity works together with
innate immunity to prevent or cure infections.

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ANTIGENS

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 DEFINITIONS
• Immunogen - A substance that induces a specific immune
response.
• Antigen (Ag) - A substance that reacts with the products of a
specific immune response.
• Hapten - A substance that is non-immunogenic but which can
react with the products of a specific immune response.
Haptens are small molecules which could never induce an
immune response when administered by themselves but which
can when coupled to a carrier molecule.
• Free haptens, however, can react with products of the immune
response after such products have been elicited. Haptens have
the property of antigenicity but not immunogenicity.
• Adjuvants -Substances that can enhance the immune response to
an immunogen.
• Epitope or Antigenic Determinant: a portion of an antigen that
combines with the products of a specific immune response.
• Antibody (Ab): A specific protein which is produced in
response to an immunogen and which reacts with an antigen. 27
 FACTORS INFLUENCING IMMUNOGENICITY
A- Contribution of the Immunogen
1.Foreignness - The immune system normally discriminates
between self and non-self such that only foreign molecules are
immunogenic.
2.Size - There is not absolute size above which a substance
will be immunogenic. However, in general, the larger the
molecule the more immunogenic it is likely to be.
3.Chemical Composition - In general, the more complex the
substance is chemically the more immunogenic it will be. The
antigenic determinants are created by the primary sequence of
residues in the polymer and/or by the secondary, tertiary or
quaternary structure of the molecule.
4.Physical form - In general particulate antigens are more
immunogenic than soluble ones and denatured antigens more
immunogenic than the native form.
5.Degradability - Antigens that are easily phagocytosed are
generally more immunogenic. This is because for most antigens
(T-dependant antigens, see below) the development of an
immune response requires that the antigen be phagocytosed,
processed and presented to helper T cells by an antigen 28
presenting cell (APC).
 B. Contribution of the Biological System
(host factors)
1. Genetic Factors - Some substances are
immunogenic in one species but not in another.
Similarly, some substances are immunogenic in
one individual but not in others (i.e. responders
and non-responders).
• The species or individuals may lack or have altered genes
that code for the receptors for antigen on B cells and T
cells or they may not have the appropriate genes needed
for the APC to present antigen to the helper T cells.

2. Age - Age can also influence immunogenicity.

Usually the very young and the very old have a
diminished ability to mount an immune response in
response to an immunogen.
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 C. Method of Administration
1. Dose - The dose of administration of an immunogen
can influence its immunogenicity.
– There is a dose of antigen above or below which
the immune response will not be optimal.
2. Route - Generally the subcutaneous route is better
than the intravenous or intra gastric routes.
– The route of antigen administration can also alter
the nature of the response
3. Adjuvants -Substances that can enhance the immune
response to an immunogen are called adjuvants.
– The use of adjuvants, however, is often hampered
by undesirable side effects such as fever and
inflammation.
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 III. CHEMICAL NATURE OF
IMMUNOGENS
A. Proteins -The vast majority of immunogens are proteins.
These may be pure proteins or they may be glycoproteins
or lipoproteins. In general, proteins are usually very good
immunogens.
B. Polysaccharides - Pure polysaccharides and
lipopolysaccharides are good immunogens.
C. Nucleic Acids - Nucleic acids are usually poorly
immunogenic. However they may become immunogenic
when they are single stranded or complexed with
proteins.
D. Lipids - In general lipids are non-immunogenic, although
they may be haptens.
• Some glycolipids and phospholipids can stimulate T cells 31
and produce a cell-mediated immune response.
 IV. TYPES OF ANTIGENS
A. T-independent Antigens – T-independent antigens are
antigens which can directly stimulate the B cells to
produce antibody without the requirement for T cell help.
• In general, polysaccharides are T-independent antigens.
• The responses to these antigens differ from the
responses to other antigens.
B. T-dependent Antigens – T-dependent antigens are those
that do not directly stimulate the production of antibody
without the help of T cells.
• Proteins are T-dependent antigens.
• Structurally these antigens are characterized by a few
copies of many different antigenic determinants.

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A B
 Differences between antigen and super antigen

• Antigenic peptides are processed within the cell and presented on the
cell surface in association with class II MHC molecules.
• They then trigger the T-cell receptor on a T lymphocyte.
• Super antigens are not processed but bind to the class II MHC protein
and to the V beta chain of the T cell receptor.
• A given super antigen activates a distinct class of T cells that express
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a certain V beta chain.