Immunity to infections.

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Immunity to infections.

• Prof. Mohamed Osman Gad El Rab.
• College of Medicine KKUH.

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Classification of immunity.

• classification of acquired immunity.
• active.
  passive.
• natural. artificial. natural.
  artificial.
• infections. immuniz. Maternal
  immuno -
• IgG.
  therapy.

type of immunity generated by the immune system
generated outside the body, NOT from the immune
system
Subclinical. Clinical.
Vaccines.
IgG from mother to fetus.
Ready made antibodies .
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General features

• First encounter with any microbe (at any age)
• Lead to Primary immune response.
• which include 4 phases
• 1. lag (preparation) (no
  antibodies)
• 2. log. (antibodies appear )
• 3. plateau.( no more synthesis )
• 4. decline.( antibody disappear
  ).
• (decline Is fast compared to 2ry response)

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plateau
decline
Antibody level
log
phases
lag
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Primary immune response

• 1. takes a longer time ( recognition of
  antigen,
• differentiation proliferation of
  cells ) .
• 2. antibody class present is mainly IgM .
• IgM is the first to be produced in primary
  response
• 3. memory cells generated .

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General features

• Second encounter with same microbe
• Secondary immune response
• 1.require small amount of antigen.
• 2. fast reaction ( memory cells ).
• 3. high levels of antibody ( IgG
  ). IgG appears in 2ry exposure

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Nature of infecting microbe determine type of
response .

• extracellular microbes .
• ( bacteria)
• Th2 helper cells.
• antibody- mediated immunity.

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• intracellular microbes .
• ( viruses , intracellular bacteria ,
  fungi )
• Th1 helper cells .
• cell- mediated immunity .

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Th1 , Th2 cells down-regulate each other.

• 1. each cell type secrete different
• cytokines.
• 2. balance between Th1 Th2
• determine the clinical presentation of
• the disease .

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The balance between TH1 TH2
is important in immunity. It
determine the clinical
presentation of the disease .
Macrophages (Antigen Presenting Cell)
TH cell
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Many factors influence immune response to
infections

• 1. structure of the microbe antigen
• How strongly the antigen stimulates a response
  (depends on some specific amino acid sequences)
• Strong antigen ? induce immune system more,
• weak antigen? takes more time to induce immune
  system (e.g. HIV)
• 2. dose of infection (optimum dose, good
  response)
• 3. route of entry into the tissues
  (determine
• site of reaction)
• To reduce the effect of an antigen which affects
  a specific site, cover the site of entry leading
  to that site.
• e.g. if an antigen affects the lung, to protect
  against this antigen expose the nasal airway
  less.
• 4. host factors - genetic constitution
• - age

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Immunity to bacterial infections

• extracellular
  intracellular
• protection by
• antibody-mediated cell-mediated
• immunity immunity
  

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Adherence
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Penetration into the host Cell
Salmonella entering epithelial cells via
invasins
Figure 15.2
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protective functions of antibodies

• 1. neutralizing action (mediated by
  antibodies)
• - prevent pathogens from binding to
• tissues
• prevent the action of toxins
• So (covers the receptors on the toxin or virus)
• 2. activate complement
• 3. stimulate phagocytosis
• 4. stimulate NK-cell-mediated killing
• 2,3,4 activated by ( antibody-antigen reaction )

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Protective functions of antibodies.
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microbial strategies to avoid the immune
system

• e.g. Pneumococcus
• has large polysaccharide coat
• ????? ??????? _
• not recognised by immune system
• can evade phagocytosis
• Mycobacteria
• have waxy coat secrete catalase
• can block respiratory burst by catalase

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In chronic intracellular infections e.g.
T.B. excessive CMI responses lead to
granuloma formation
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Granuloma formation ( T.B. )
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Complications of immune responses

• In some cases , disease is not caused by
• the bacteria but rather by the immune
• response
• So the complications and the problems in the
  disease are caused by the immune system ?

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Endotoxins of gram ve bacteria
(lipopolysaccharides) activate macrophages
which releasehigh levels of IL-1, TNF -
alpha, these may cause
Septic shock (due to septicemia, infection in
blood)Treatment anti-TNF, anti-IL1
Examples
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• In staphylococcal ( food poisoning ) ,
• enterotoxins ( a protein toxin released by a
  microorganism in the intestine ) act as
  superantigens
• and cause direct massive T-cell
  activation
• This may cause
• Toxic shock syndrome
• Superantigens activate T-cells directly, without
  the need of APC for activation

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NOTE

• Septic shock is caused by septicemia, which is a
  state of high bacteria in blood. So bacteria is
  the direct cause of septic shock.
• Toxic shock syndrome is caused by toxins

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immunity to viral infections

• Initially
• 1. Interferon, secreted by
• - infected cells
  (macrophages)
• - inflammatory cells (T
  lymphocytes)
• can
• 1- directly kill viruses
• 2- makes cell wall of our body resistant to
  viruses
• 2. NK- cells

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Antibody- mediated immunity

• Anti-viral antibodies
• 1. Prevent spread during acute infection
• (or vaccination)
• 2. Protect against re-infection

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adaptive immune mechanisms

• Cell-mediated immunity
• activation of CD8 T-cells.
• - inhibit viral replication.
• - kill infected cells .

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Viruses can evade host defenses.

• 1. Hepatitis C virus
• overcome (anti viral) effect of INFs
• by blocking the action of protein kinase
• Protein kinase is a metabolic pathway for killing
  viruses inside cells
• 2. Adenoviruses CMV ( a type of Herpes
  virus )
• reduce surface expression of MHC-1

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Influenza virus
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1. Antigenic drift (random mutations in
genes)gradual minor change in HA NA small
changes in the genes of one DNA stretch of one
virus to evade the immune system

• 2. Antigenic shift (re assortment or mixing of
  genetic material)
• sudden major change in HA NA
• ( new subtypes emerge )
• Fusion between 2 DNA stretches from more than
  one virus that change the virus into a new form
• So a strange DNA is inserted into the virus to
  form a new set of DNA, so a new virus is formed

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• Immunity to parasitic infections

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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
• effective

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Immunity to Malaria

• Caused by genus Plasmodium.
• P. falciparum is the most virulent
  prevalent
• Infect 10 of the population.
• Causes 1 2 million deaths every year
• Have a complex life cycle
• (many antigens appear during infection)
• Vaccines are difficult for malaria, because it
  changes its antigens in each stage

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Life cycle of malaria
3-stages.
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During the life- cycle, many antigensappear

• Infection begin with mosquito bite
• Sporozoites enter the blood disappear
• within 30 min
• Migrate to the liver after one week
• release merozoites which infect RBCs

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Sporozoites stay for only 30 min. in the
blood, therefore induce a poor immune
response

• The intracellular stage in the liver cells
• and RBC, reduce the degree of immune
• activation generated by the pathogen
• (note that RBC does not have MHC)

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So , in case of malaria there is poor immune
response because 1- the Sporozoites stay in
blood for short time ( 30 min ) to induce immune
response 2- RBCs does not have MHC , so there is
no presentation
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Immunity to parasitic worms (helminthes)

• Helminthes are large multicellular
• organisms e.g. Schistosoma (Bilharzia)
• Have complex life- cycle

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• Cercaria enter the blood stream and
  become schistosomules which enter
• capilleries then pass to the lungs liver
  
• and become adult worms

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Humoral immune responses to parasitesare
characterized by

• 1. Elevated IgE
• 2. Blood eosinophilia
• Eosinophils mediate ADCC (antibody
  directed cellular cytotoxicity) to
• damage the parasite