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Immunity and infection
Introduction
• The development of an infectious disease in an individual
involves complex interactions between the microbe and the
host. The key events during infection include:
–
–
–
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entry of the microbe
invasion and colonization of host tissues
evasion of host immunity
tissue injury or functional impairment
• Microbes produce disease by:
– directly killing the host cells they infect, or
– liberating toxins that can cause tissue damage and functional
derangements in neighboring or distant cells and tissues that
are not infected, or
– stimulating immune responses that injure both the infected
tissues and normal tissues.
General Features of Immune Responses to
Microbes
• Defense against microbes is mediated by the
effector mechanisms of innate and adaptive
immunity.
•
• The immune system responds in specialized and
distinct ways to different types of microbes to most
effectively combat these infectious agents.
• The survival and pathogenicity of microbes in a host
are critically influenced by the ability of the
microbes to evade or resist the effector mechanisms
of immunity.
The extracellular bacteria
• Extracellular bacteria defined as the bacteria that
capable to replicate outside the host cells, e.g. in
blood, connective tissue, airway/gastrointestinal
tract
• The bacteria may either
• 1) induce inflammation or
• 2) produce toxins that destruct the body tissue
• E.g. of toxin: Endotoxin of gram-negative or
lipopolysaccharide (LPS).
Innate immunity to extracellular
bacteria
• Principles:
• Complement activation
• Activation of phagocytes and inflammatory
response
Nonspecific immune system

The complement system
 The complement system is a primary mediator of the humoral immune
response that enables the body to produce an inflammatory response,
lyse foreign cells, and increase phagocytosis.

The complement system, consists of a group of proteins that normally
are present in the circulation as functionally inactive precursors. These
proteins make up 10% to 15% of the plasma protein fraction.

For a complement reaction to occur, the complement components must
be activated in the proper sequence.

Uncontrolled activation of the complement system is prevented by
inhibitor proteins.
Complement activation
The classic pathway of complement activation is initiated by
antibody bound to antigens on the surface of microbes.
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The alternate and the lectin pathways
part of the innate immune defenses.
do not use antibodies and are

The alternate pathway of complement activation is initiated by the
interaction with certain polysaccharide molecules characteristic of
bacterial surfaces.

The lectin-mediated pathway is initiated following the binding of a
mannose-binding protein to mannose-containing molecules
commonly present on the surface of bacteria and yeast.
The activation of the three pathways produces similar effects on C3 and
subsequent complement proteins.
Complement activation
Classic Pathway
Adaptive immunity to extracellular
bacteria
• Humoral immunity: block infection, eliminate
microbes and neutralize toxins
•
The B-cell response to antigens has two stages:
– Primary immune response:
• When B cells first encounter an antigen, the antigen attaches to a receptor,
stimulating the B cells.
• Some B cells change into memory cells, which remember that specific antigen, and
others change into plasma cells. Helper T cells help B cells in this process.
• Plasma cells produce antibodies that are specific to the antigen that stimulated
their production. After the first encounter with an antigen, production of enough of
the specific antibody takes several days. Thus, the primary immune response is
slow.
– Secondary immune response
• Whenever B cells encounter the antigen again, memory B cells very rapidly
recognize the antigen, multiply, change into plasma cells, and produce antibodies.
This response is quick and very effective.
Primary and secondary phases of the humoral
immune response to the same antigen.
Humoral Immunity
Cellular Immunity
• D4+ produces cytokines that induce local
inflammation and activate phagocytic function
and microbicidal activities of Macrophages and
Neutrophiles
Polyclonal activation of T cells by
bacterial superantigens
Extracellular bacteria evasion
• A mechanism used by bacteria to evade
humoral immunity.
• Genetic variation of surface antigen (E. coli, N.
gonorrhoeae, S. typhimurium)
• Resistance to phagocytes (Pneumococcus)
• Destruction to ROS? ?? (Catalase producing
Staphylococci)
Immunity to
Intracellular Bacteria
Intracellular bacteria
• A characteristic of facultative intracellular
bacteria is their ability to survive even replicate
within phagocytes.
• Requires cell-mediated immunity
Innate and Adaptive Immunity
• The innate immune response to intracellular
bacteria consists mainly of phagocytes and NK
(natural killer) cells.
• The major adaptive-protective immune response
against intracellular bacteria is cell-mediated
immunity.
• The macrophage activation in response to
intracellular microbes is capable of causing tissue
injury.
Mechanisms of Immune Evasion by Bacteria
• Inhibition of phagolysosome
formation
(Mycobacterium
tuberculosis,
Legionella
pneumophila)
• Inactivating reactive oxygen and
nitrogen
intermediates
Mycobacterium leprae
•
• Disruption
of
phagosome
membrane,
escape
into
cytoplasm
Listeria
monocytogenes
(hemolysin
protein)
Intracellular bacteria
Microbe
Human Diseases
Pathogenicity
Mycobacteria species
Tuberculosis, Leprosy
Macrophage activation,
granulomatous
inflammation, tissue
destruction
Listeria monocytogenes
Listeriosis
Listeriolysin damages cell
membrane
Legionella pneumophila
Legionnaires’ disease
Cytotoxin lyses cells
Immunity to Intracellular Bacteria
IL-2
IFN-γ
The type of immune response stimulated by bacteria depends on whether the
bacteria are live or dead and whether they grow inside or outside cells.
Viruses
• Obligatory intercellular pathogens that
replicate within cells.
• Use the nucleic acid and protein synthetic
machineries of the host cell.
• Infect a variety of cell populations by
utilizing normal cell surface molecules as
receptors to enter cell.
Innate Immune Response to Viruses
• Viral infection directly stimulates the
production of interferons (INF).
• Interferons are antiviral proteins, or glycoproteins
produced by several types of cells in response to
viral infection.
• INFα by leucocytes
• INFβ by fibroblast
• INFγ by natural killers (NK) cells
• Natural killer (NK) cells lyse a wide
variety of virally infected cells.
Specific Immune Response to Viruses
• Mediated by a combination of humoral and cell
mediated immune mechanisms.
• Humoral mediated immune response.
• Antibodies specific for viral surface antigens are often
crucial in containing the spread of a virus during acute
infection and in protecting against re-infection.
• Specific antibodies are important in defense against
viruses early in the course of infection and in defense
against cytopathic ??? viruses that are liberated from
lysed infected cells.
Opsonization
1. Opsonizing
antibodies may
enhance
phagocytic
clearance of viral
particles.
Specific Immune Response to Viruses
• Cell-mediated immune responses.
• Most important in host defense, once a viral infection is
established.
• CD8+ Tc cells (Cytotoxic T lymphocytes; CTLs) and CD4+
helper T lymphocytes are the main components of cell
mediated antiviral defense.
CD8+ T and CD4+ T
CTL activating macrophage function
Tissue Injury
• In some cases, infections with non-cytopathic
viruses, CTLs may be responsible for tissue
damage to the host.
Evasion of Immune Mechanisms by
Viruses
• Viruses have evolved numerous mechanisms
for evading host immunity.
• A number of viruses have strategies to evade
complement-mediated destruction.
Evasion of Immune Mechanisms by
Viruses
• Viruses can also escape immune attack by
changing their antigens.
• A large number of viruses evade the immune
response by causing generalized
immunosuppression.
Parasites
• In infectious disease terminology, “ parasitic
infection” refers to infection with animal
parasites, such as protozoa, helminthes, and
ectoparasites.
– Humans are only part of the complex life cycle of
parasites.
Innate Immunity Parasites
•
Protozoa and helminthic parasites that
enter the blood stream or tissue are often
able to survive and replicate because they
are resistant to host innate immune
responses.
–
–
Parasites in humane host are usually resistant
to complement.
Macrophages can phagocytose protozoa, but
the tegument of helminthic parasites makes
them resistant to the cytocidal effects of both
neutrophils and macrophages.
Specific Immunity to Parasites
• Different parasites elicit quite distinct specific
immune responses.
– Cell-mediated immunity is the principal defense against
protozoa that survive within macrophages.
– Protozoa that replicate inside cells and lyse host cells
stimulate specific CTL responses, similar to cytopathic
viruses.
– IgE antibodies and eosinophils mediate defense against
many helminthic infections.
Evasion of Immune Mechanisms by
Parasites
• Evolutionary adaptations give parasites their
ability to evade and resist immune responses.
– Some parasites survive and replicate inside cells.
– Others develop cysts that are resistant to immune
responses.
– Antigen masking is an effective form of immune
response evasion by some parasites.
– Parasites can develop a tegument that is resistant
to damage by antibodies and complement or
CTLs.
– Some parasites have mechanisms for surface
antigen variation
• The End