IMMUNITY TO INFECTION

IMMUNITY TO VIRUSES
IMMUNITY TO PARASITES

BY
NARUHURA GEORGINA
 OBJECTIVES
By the end of the lecture, students should be able to:
Discuss innate and adaptive immunity against viruses
Explain the strategies evolved by viruses to evade the
immune response.
List the pathological consequences of immune
responses against viruses
Discuss immunity against parasites
Explain the strategies evolved by parasites to evade
the immune response.
List the pathological consequences of immune
responses against parasites.
 Innate immunity to viruses
Innate defences are triggered following recognition
of pathogen associated molecular patters(PAMPs)
by the Pattern recognition receptors (PRR)

Innate immune responses are mediated by

Antimicrobial peptides, type I interferons (IFNs),
dendritic cells(DCs), natural killer (NK) cells, and
(macrophages) to restrict the early stages of
infection, delay spread of virus and promote the
activaton of adaptive responses.
 Viral PRRs and corresponding PAMPs

PRR (on human cell) PAMP(on virus)

TRL2 Viral hemagglutinin
TRL3 Viral double stranded RNA
TRL4 Viral envelope protein
TRL7 Viral single stranded RNA
TRL8 Viral single stranded RNA
 Type I interferons(IFNs)
Type I IFNs exert direct anti viral activity and also
activate other innate and adaptive responses.

Type I IFNs can be produced by almost any cell

type in the body if it becomes infected with a
virus.

There are also specialized interferon-producing

cells, (plasmacytoid DCs), which can be triggered
to produce high levels of type I IFN following
exposure to virus without themselves becoming
infected.
 Type I interferons (IFNs)

Type I IFNs
mediate direct
antiviral effects
and play an
important role in

activating the

anti viral
defenses
 Natural Killer cells
NK cells are cytotoxic for virally-infected cells.

NK cells act to combat virus replication directly by

recognizing and killing infected cells.

They also produce cytokines such as IFN gamma and

TNF alpha and mediate important immunomodulatory
effects stimulating the activation of macrophages via
IFN gamma and regulating DC responses.

NK cells are one of the principal mediators of antibody

dependent cell mediated cytotoxicity (ADCC).
 Macrophages
Macrophages help to kill the virus in the following
ways:phagocytosis of virus:

Phagocytosis:
Macrophages engulf and destroy viruses through a process
called phagocytosis.

The engulfed virus is then contained within a phagosome,

which fuses with lysosomes to form a phagolysosome.

The acidic environment of the phagolysosome and the

activity of lysosomal enzymes help to degrade and inactivate
the virus.

Production of antiviral molecules such as TNF alpha, nitric oxide,

and IFN alpha.
 Microbicidal peptides
Microbicidal peptides have broad-spectrum antiviral
effects.

For example, respiratory secretions are rich in the

collectin surfactant proteins (SP)-A and SP-D.

These molecules bind to carbohydrates on a range of

pathogens including influenza virus where they adhere to
the hemagglutinin protein(HA) resulting in virus
neutralization.

Other families of antimicrobial peptides with antiviral

activity include the defensins and the related
 Adaptive immunity to viruses
As a viral infection proceeds, the adaptive immune
response unfolds.
Antibodies can limit viral spread or reinfection.
T cells mediate viral immunity in several ways:

CD8+ T cells destroy virus-infected cells or cure them of

infection;

CD4+ T cells promote antibody and CD8+ T cell

responses and are a major effector cell population in
the response to some virus infections.
 CD8+ T cells
CD8 + T cells target virus-infected cells:
CD8+ T cells kill virus infected cells through the release
of perforin, granzymes, and other cytolytic proteins.

They trigger the death of infected ells through binding

of soluble factors (e.g. INF alpha) or ligands they express
(e.g. fasL) or cell-surface receptors (such as fas) that
signal the cell to undergo apoptosis.

They produce soluble factors such as IFN gamma and/or

INF alpha that can 'cure’ infection with some viruses
e.g. hepatitis B virus) without death of the cell.
 C4+ T cells
Most of the antibody responses are T-dependent,
requiring the presence of helper CD4+ T cells for class
switching and affinity maturation.

CD4+ T cells also help in the induction of CD8+ cell

responses and in the recruitment and activation of
macrophages to sites of virus infection.
Antibodies
 Strategies of Immune Evasion by Viruses
Avoidance of recognition by host immune defenses:
Latency,
Infection of ‘immune privileged’ sites,
Antigenic variation.
Avoid recognition by T cells by reducing MHC expression
on infected cells.

Resisting control by immune effector mechanisms:

impairing production of typeI IFNs production of soluble
IFN receptors (e.g.poxviruses); interference with IFN
signaling (e.g.paramyxoviruses);

Infecting APCs.
 Pathological consequences of immune responses
against viruses
Excessive cytokine production drive an aggressive
inflammatory response that can result in massive tissue
damage e.g(pneumonia) leading to death among SURs
patients.

Viral infection may provoke autoimmunity.

Virus-specific T-cell responses can cause severe tissue

damage.
 IMMUNITY TO PARASITES
Parasitic infections are often chronic and affect many
people.

The innate and adaptive immune responses are co-evolving

to allow mammals to identify and eliminate parasites.

Some key components of innate immunity that contribute

to the defense against parasites: physical barrier, Pattern
recognition receptors, Inflammatory response, complement
system etc
 Innate immunity:Physical barriers

The skin and mucous membranes act as physical barriers,

preventing the entry of parasites into the body.

Additionally, mucous secretions and cilia in the

respiratory tract and the movement of the
gastrointestinal tract help to expel parasites.
 PRR

Innate immune recognition relies on pattern recognition

receptors (PRRs) that have evolved to recognize pathogen
associated molecular patterns(PAMPs) such as Toll-like
receptors, pentraxin, C-type lectin etc
 Natural killer (NK) cells

NK cells are a type of lymphocyte that can directly kill

infected cells, including those infected by parasites.

They recognize changes in the surface proteins of

infected cells and induce cell death through
mechanisms like releasing cytotoxic granules or
promoting apoptosis.
 Complement system
The complement system consists of
a group of proteins that can be
activated in response to parasite
invasion.

The activated complement proteins

can directly destroy parasites,
enhance
phagocytosis,
& induce inflammation.
 Inflammatory response:
Parasite infections trigger an inflammatory response
characterized by the release of pro-inflammatory
cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6),
and tumor necrosis factor-alpha (TNF-α).

These cytokines help recruit immune cells to the site of

infection, enhance phagocytosis, and activate other
effector mechanisms.
 Adaptive immunity to parasites
T and B cells are pivotal in the development of immunity.
B cells play key roles in regulating and controlling immunity
to parasites. For example:
B cells and antibodies are required for resistance to the
parasitic gastrointestinal nematode. Passive transfer of IgG
can protect people from malaria.
Both CD4 and CD8 T cells are needed for protection from
some parasites
 Adaptive immunity to parasites
CD4 + and CD8+ T cells protect against different phases of
plasmodium infection:
CD4+ T cells mediate immunity against blood stage.
CD8+ T cells protect against the liver stage
PPlasmodium.
CD8+ T cells secrete IFN gamma which inhibits the
multiplication of parasites within hepatocytes.
The cytokines produced by CD4+ T cells can be important
in determining the outcome of infection.
TH1 responses mediate killing of intracellular pathogens;
TH2 responses eliminate extracellular ones.
 Adaptive immunity to parasites

T cell responses to protozoa depend on the species.

The immune response to worms depends up on TH2-
secreted cytokines.
Some worm infections deviate the immune response.
 Antiparasitic immune effector cells:
Macrophages

Macrophages secrete many cytotoxic factors, enabling

them to kill parasites without ingesting them.
When activated by cytokines, macrophages can kill
relativel larger parasites, such as the larval stages of the
schistosome. Macrophages also:
Act as killer cells through ADCC specific IgG and IgE, for
instance, enhance their ability to kill schistosomules;
secrete cytokines, such as TNF alpha and IL1, which
interact with other types of cells, for example rendering
hepatocytes resistant to malarial parasites.
 Neutrophils
Neutrophils can kill large and small parasites

Extracellular destruction by neutrophils is mediated by

hydrogen peroxide, whereas granular components
(Defensins, seprocidins, and cathelicidins) are involved in
the intracellular destruction of ingested organisms.

Like macrophages, neutrophils bear Fc and complement

receptors and can participate in antibody-dependent
cytotoxic reactions to kill for example, the larvae of
several species of nematodes.
 Eosinophils & mast cells
Eosinophils degranulate and their activities are
enhanced by cytokines such as TNF alpha.
Eosinophils and mast cells can act together.
There is IgE-dependent degranulation of mast cells and
the release of mediators that selectively attract
eosinophils to the site of infection and further enhance
their activity.
Activated Mast cells can also degranulate to control
gastrointestinal helminths.
strategies evolved by parasites to evade the
immune response

Intracellular habitat
Plasmodium
Trypanosomes
Leishmania spp

Encystment
Toxopasmagondii
Trypanosoma cruzi
strategies evolved by parasites to evade the immune
response
Resistance to microbicidal products of phagocytes
Leishmania donovani.

Masking of antigens
Schistosomes

Variation of antigen
Trypanosomes
Plasmodium
 strategies evolved by parasites to evade the
immune response
Sharing of antigens between parasite and host(molecular
mimicry)
Schistosomes

Continuous turnover and release of surface antigens of

parasite
Schistosomes

Suppression of immune system

Trichinella spiralis
Schistosomes
 Immuno-pathologicalconsequences of
parasitic infections
In malaria, African trypanosomiasis, and visceral
leishmaniasis, the increased number and heightened
activity of macrophages and lymphocytes in the liver and
spleen leads to enlargement of those organs.

The gross changes occurring in individuals with

elephantiasis are probably caused by immunopathological
responses to adult filariae in the lymphatics.

The formation of immune complexes is common; they may

be deposited in the kidney, as in the nephrotic syndrome
of malaria, and may give rise to many other pathological
changes.
Immuno-pathological consequences of parasitic infections

The IgE of worm infections can have severe effects on the

host due to release of mast-cell mediators.
Anaphylactic shock may occur when a hydatid cyst ruptures.
Asthma-like reactions occur in Toxocara canis infections, and
in tropical pulmonary eosinophilia when filarial worms
migrate through the lungs.
Autoantibodies have been detected against red blood cells,
lymphocytes (e.g. in trypanosomiasis and in malaria).
Antibodies against the parasite may cross-react with host
tissues. For example, the chronic cardiomyopathy, enlarged
oesophagus and megacolon that occur in Chagas' disease are
thought to result from the autoimmune effects on nerve
ganglia of antibody and of cytotoxic T cells that cross-react
with T. cruzi.
 Reference

Roitt I., Brostoff J. and Male D., Immunology, 8th Edition,

2013, chapter 13; page 211 to 222 and chapter 15; page 243
to 261