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Immunity to infectious
Prof. Mohamed Osman Gad El Rab.
College of Medicine& KKUH.
Acquired immunity.
of immunity.
infections. immuniz.
immuno therapy.
• Immunity to viral infections .
Innate (natural) immunity:
many viruses induce :
1. production of type 1 interferons.
( INF- alpha & INF - beta.)
2. activation of NK - cells .
dsRNA produced during viral
replication induce the expression of
interferons by the infected cells.
* monocytes , macrophages & fibroblasts
also synthesize interferons .
Viruses initiate infection by
binding to specific host - cell
membrane molecules .
• e.g.
1. influenza virus bind to cell membrane
glycoproteins .
2. rhinoviruses bind to intercellular
adhesion molecules (ICAMs).
Mechanism of action :
Interferons bind to receptors that
JAK-STAT pathways.
These induce several genes .
1. One gene activate a ribonuclease that
degrade viral RNA .
2. Other genes activate protein
kinases which inhibit protein
synthesis .
3. binding of INFs to NK-cells induce
lytic activity .
* IL-12 produced by macrophages also
enhance NK-cell activity .
Antibody- mediated immunity :
• Anti-viral antibodies :
1. prevent spread during acute infection.
2. protect against reinfection .
Protective functions of antibodies :
1. secretory IgA blocks viral attachment .
2. complement - fixing antibodies may
cause lysis of enveloped viruses
3.IgM antibody agglutinate viral particles .
Cell – mediated immunity is
important for control &
clearance of viral infections .
CTL activity arises within 3 - 4 days,
peak by 7-10 days & then decline
when the infection is cleared .
can evade
1. Hepatitis C virus :
overcome anti - viral effect of INFs
blocking the action of protein kinase.
2.Adenoviruses & CMV :
reduce surface expression of MHC-1.
3. Measles ,CMV & HIV :
reduce MHC -11 levels .
4. A large no. of viruses cause
generalized immunosuppression.
e.g. mumps , measles , EBV., CMV.,
& HIV.
Influenza virus .
Antigenic variation of influenza
virus .
• In 1918-1919 an influenza pandemic
killed over 20 million people .
The structure of the virus contain :
Hemagglutinins (HA ).
Neuraminidase (NA ).
Shifting Nature of Influenza
• Antigenic drift – small, ceaseless changes
in the genetic structure. New strains
continually replace old strains.
• Antigenic shift – major change, usually
occurs when species hosting virus trade
viral genes. Novel strain appears without
natural immunity in host population.
1. Antigenic drift :
gradual minor change in HA & NA.
2. Antigenic shift :
sudden major change in HA & NA .
( new subtype emerge )
1918 Hemagglutinin Causes Severe
Lung Damage.
Kobasa et al. Nature 2004;431:703
Example: If MHC X was the only type of MHC molecule
Pathogen that
evades MHC X
Survival of
Population threatened with
• Immunity to bacterial infections.
• If the inoculum (dose ) is small and the
virulence of the bacteria is low .
Tissue phagocytes may eliminate
the bacteria .
The humoral response (antibody) is the
main protective response
extracellular bacteria .
• Antibodies act in several ways :
1. neutralize toxins .
2.activate complement .
- generates anaphylatoxins.
-release chemotactic agents .
Protective functions of antibodies.
Intracellular bacteria :
• Initially activate NK – cells which
provide early defense .
Final control is by :
cell - mediated immunity .
( this involve activated macrophages )
Cell-mediated immunity involve activated
Bacteria can by-pass host defense:
• 4 steps in bacterial infections :
1. attachment .(adherence).
2. proliferation .
3. invasion of host tissues .
4. toxin - induced damage.
Penetration into the Host Cell
Salmonella entering epithelial cells via invasins
Figure 15.2
Secretory IgA block attachment , but
some bacteria secrete proteases that
break IgA .
2. Opsonization & phagocytosis prevent
proliferation , but some bacterial
surface structures inhibit phagocytosis,
( polyssacharide capsule ,Strp.pneum.)
Strep.pneumonae. Inhibit phagocytosis.
3. Some bacteria resist complement
lysis .
4. Mycobacteria survive intracellularly by
resisting oxidative attack ,some prevent
lysosomal fusion .
Complications of immune responses .
In some cases disease is not caused by
the bacteria but rather by the immune
Endotoxins of gram –ve bacteria
activate macrophages which release
high levels of IL-1, & TNF - alpha,
these may cause :
Septic shock .
2. In staphylococcal food – poisoning ,
enterotoxins act as superantigens
and cause direct massive T-cell
activation . This may cause:
Toxic shock syndrome .
Contrast the nature and effects of exotoxins and endotoxins.
Figure 15.4b
Figure 15.4a
3.Complications of streptococcus pyogenes
• 1. Rheumatic fever :antibodies formed against antigen in
the strep. cell wall cross –react with the sacrolemma of
Human heart .Granuloma form in the heart (Aschoffs
2. Rheumatic heart disease :repeated attacks by strep.
with different M types can result in damage to the heart
valves.( certain children have a genetic predisposition
to this immune-mediated disease ). ( high A.S.O. titer ).
• 3. Acute glomerulonephritis :
antibodies to strep . components combine to form
immune- complexes which then deposit in the kidney
glomeruli .
4. In chronic intracellular infections e.g.
T.B. excessive CMI responses lead
to granuloma formation .
Granuloma formation ( T.B. )
The balance between TH1 & TH2 is
important in immunity. It determine the clinical
presentation of the disease .
5. Immunological response in leprosy :
The response decide the type of disease :
1.In tuberculoid leprosy the patient mount an effective
cell-mediated response.Macrophages destroy the bacilli
and contain the infection .
2. In lepromatous leprosy : the patient is unable to produce
a cell-mediated response and organisms multiply and
spread in the tissues >
• Immunity to parasitic infections:
• A. Protozoal diseases .
These are unicellular organisms .
e.g. malaria , trypansomiasis , toxoplasma,
* They have complex life - cycles.
some stages are free in the blood ,
other stages are intracellular.
The type of the immune response
depend on the location of the
parasite in the host .
In the blood antibodies may be effective
In the intracellular stage CMI may be
Immunity to Malaria:
• Caused by genus Plasmodium.
• P.falciparum is the most virulent &
• Infect 10% of the population.
• Causes 1 – 2 million deaths every year.
• Have a complex life – cycle .
Life cycle of malaria :
During the life- cycle, many antigens
appear :
• Infection begin with mosquito bite.
• Sporozoites enter the blood & disappear
within 30 min.
* Migrate to the liver & after 1 week
release merozoites which infect RBCs.
Sporozoites stay for only 30 min. in the
blood, therefore induce a poor immune
• The intracellular stage in the liver cells
and RBC ,reduce the degree of immune
activation generated by the pathogen.
In endemic areas:
• Only 22% of the children have detectable
antibodies to sporozoites.
• In adults 84% have such antibodies.
• In general, the degree of immunity to
Malaria is not complete .
Trypansomiasis ( sleeping sickness).
• As the parasite
multiply , an effective
antibody response
develop to
glycoprotein coat called variant surface
glycoprotein (VSG).
These antibodies eliminate
most of
Parasite from the blood by :
1. complement lysis.
2. opsonization & phagocytosis .
Trypansomes, (T. cruz,)
However , 1% of the parasite with different
antigen (VSG ) escape the antibody
These proliferate and a new wave of
parasites invade the blood .
• This is called :
antigenic shifts.
(a characteristic feature of Trypansomes ).
Immunity to parasitic worms (helminths):
• Helminths are large multicellular
organisms e.g. Schistosoma (Bilharzia ).
• Have complex life- cycle .
• Cercaria enter the blood stream and
become schistosomules which enter
capilleries.then pass to the lungs & liver.
then become adult worms.
Immune responses are not sufficient
to eliminate the adult worms .
• Adult worms evade immune responses
by coating themselves by host
glycoproteins .
Humoral immune responses to parasites
are characterized by :
1. elevated IgE.
2. blood eosinophilia .
Eosinophils mediate ADCC to
damage the parasite.
A chronic state develop in which adult
worms persist and induce cell-mediated
delayed hypersensitivity reactions
This eventually result in the formation of
large granulomas .
Immunity to fungi .
• Fungal infections of man fall into 4 types:
1.superficial mycoses .
2.subcutaneous mycoses.
3.respiratory mycoses.
4.candida albicans .
• Recovery is based on cell-mediated immunity.
• There is also evidence for neutrophil
In immunity to some respiratory mycoses.
Immunology quiz no 4.
• A12-year old girl has been receiving cytotoxic drugs for
Acute leukemia. Although there is evidence that the
leukemia is responding, she has become neutropenic
( neutrophils were less than 0.5 x10 ml ) .Early in the
evening she was found to have fever, within half an hour
she collapsed and was found to have features of sock
(tachycardia and hypotention ).
Blood was taken for culture which later grew E. coli. She
was started on antibiotics and fluid replacement .She
gradually improved during the next 12 hours .
1. What is the diagnosis of this patient ?
2. What is the predominant cell involved in this
condition ?
2. Describe the underlying immunopathology.?
• What is the recommended childhood immunization
schedule in Saudi Arabia ?
What are the indications for passive immunization ?
Mention 2 infectious and 1 non-infectious condition
for which passive immunization may be required ?
Practical points :
Routine tests in microbial serology .
1. Widal test for diagnosis of typhoid fever.
standard tube agglutination test (STA)
-patient serum in dilution mixed with
salmonella suspension .
2.A.S.O. test.
anti- streptolysin O test.
-toxin –anti-toxin neutrallization test for
diagnosis of streptococcal infections .
(patient serum neutralize toxin therefore indicator R.B.C . not lysed )
3. T.P.H.A.test.
• Treponema pallidum hemagglutination test.
-for diagnosis of syphilis.
Trypansomes,life –cycle.