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CMB2004 > L11 - Immunity against Infection: evasion of host defences & immunopathology in infection > Flashcards

L11 - Immunity against Infection: evasion of host defences & immunopathology in infection Flashcards

1
Q

Evasion mechanisms that pathogens have evolved

A
  • Concealment of antigens
  • Antigenic variation
  • Immunosuppression
  • Interference with effector mechanisms
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2
Q

Concealment of antigens

A

Pathogens evade attack by immune system by living inside cells (cloak effect)
• e.g. Schistosomes (bilharzia) – takes on the host cells so not recognised by the immune system

Or live beyond the reach of antibodies (privileged sites)
• e.g. latency of Herpes zoster virus in CNS (chicken pox -> shingles)

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3
Q

Cold sores

A

Caused by Herpes Simplex virus

Likes to live in the trigeminal nerves

Can be reactivated during periods of stress

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4
Q

What is antigenic variation?

A

Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response

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5
Q

Types of antigenic variation

A

Large number of antigenic types

Mutation (antigenic drift)

Recombination (antigenic shift)

Gene switching

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6
Q

ANTIGENIC VARIATION

Large number of antigenic types
Example

A

Streptococcus pneumoniae

  • Causes otitis media, sinusitis, bronchitis and pneumonia; also bacteremia and meningitis
  • Gram positive; surrounded by a thick polysaccharide capsule which protects it from phagocytosis
  • Antibodies to the capsule opsonise the bacteria and protect
  • Large number of different capsular types (91)
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7
Q

Streptococcus pneumoniae vaccines

A

Streptococcus pneumoniae – 23 major disease causing polysaccharide capsules (strains)

Vaccines:
• Pneumovax
• Prevnar 13

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8
Q

Pneumovax vaccine against Streptococcus pneumoniae

A

Polysaccharide vaccine (contains antigens to all 23 capsules)

Not effective in children under two or those with poor immune function (eg. HIV) – low level response – just B cell IgM response

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9
Q

Prevnar 13 vaccine against Streptococcus pneumoniae

A

Conjugate vaccine

Only 13 capsule antigens but bound to the diphtheria toxoid which is highly immunogenic but non-toxic

T cell and B cell (all Ig) response

Converts TI-2 polysaccharide antigen to a TD form

Better for children: young children cannot produce an immune response to polysaccharides

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10
Q

Why can young children not produce an immune response to polysaccharides?

A

Thought to be due to immunologic immaturity

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11
Q

ANTIGENIC VARIATION

Antigenic drift and shift
Example

A

Influenza virus

  • An RNA virus with a negative sense segmented genome
  • Can infect humans, birds and other animals
  • Causes epidemics and pandemics
  • Major surface antigens are haemagglutinin and neuraminidase
  • Can undergo antigenic drift (epidemics) and antigenic shift (pandemics)
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12
Q

What causes epidemics?

A

Antigenic drift

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13
Q

What causes pandemics?

A

Antigenic shift

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14
Q

ANTIGENIC VARIATION

Gene switching
Example

A

Trypanosoma brucei

  • Protozoal parasite that causes African sleeping sickness
  • Spread by the tsetse fly – warm climates
  • Patients undergo bouts of parasitemia
  • Correlates with changes in the major surface antigen of the trypanosome, brought about by genetic rearrangement
  • Variant-specific glycoprotein (VSG) – antibodies don’t recognise the epitope
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15
Q

IMMUNOSUPPRESION

What are the 2 types?

A

Infection of immune cells

Induction of regulatory T cells

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16
Q

IMMUNOSUPPRESION

Infection of immune cells
Example

A

HIV

  • Depletion of CD4+ cells
  • Opportunistic infections in the symptomatic phase
17
Q

IMMUNOSUPPRESION

Induction of regulatory T cells
Example

A

Helicobacter pylori

  • Gram negative bacterium that causes gastric and duodenal ulcers (also gastric adenocarcinomas)
  • Regulatory T cells may be involved in allowing it to establish a persistent infection
18
Q

What do regulatory T cells do?

A
  • Type of CD4+ cell
  • Regulate the immune system – suppress differentiation and proliferation of TH1 and TH2 cells
  • Immunosuppressive eg IL10
  • Maintain tolerance to self-antigens
  • Help prevent autoimmune disease
19
Q

Induction of regulatory T cells in Leishmania

A

Immunosuppression

  • Parasite – genus of trypanosomes
  • Vector – sand fly
  • Can hide and survive in macrophages
  • Can increase expression of Treg cells
  • Decrease immune response
20
Q

Measles virus

A

An RNA virus; disease is associated with a rash commonly accompanied by profound malaise and respiratory symptoms

Complications include secondary bacterial respiratory infections

Causes immunosuppression which can lead to secondary infections

Shown to infect dendritic cells

21
Q

Infection of dendritic cells by measles virus causes what effects?

A

Increased apoptosis

Decreased stimulation of T cells

Decreased IL-12 production (NK cells and TH1 affected – response dampened down)

22
Q

EVASION OF THE IMMUNE DEFENCES

How do pathogens interfere with effector mechanisms?

A

Molecules interfering with antibody function

Molecules interfering with complement

Molecules binding cytokines

Subvert responses by producing molecules with cytokine activity

Inhibition of phagocytic killing

23
Q

EVASION OF THE IMMUNE DEFENCES

Molecules interfering with antibody function

A

e.g IgA proteases chop up IgA (Streptococcus pneumoniae, Neisseria spp.)

Fc-binding molecules – bind to FcR on immune cells to activate them (Staphylococcal protein A; Herpes simplex virus)

24
Q

EVASION OF THE IMMUNE DEFENCES

Molecules interfering with complement

A

Enzymes that break down C3a/C5a (Pseudomonas)

Molecules that inhibit complement activation (Vaccinia/smallpox virus)

25
Q

EVASION OF THE IMMUNE DEFENCES

Molecules binding cytokines

A

E.g. Vaccinia (small pox,IFNγ)

26
Q

EVASION OF THE IMMUNE DEFENCES

Subvert responses by producing molecules with cytokine activity

A

E.g. Epstein Barr Virus produces vIL-10 (downregulates TH1 Response)

Epstein Barr virus causes glandular fever

IL-10 made by T-regs – downregulates response using vIL-10 – increases chance of the virus surviving

27
Q

EVASION OF THE IMMUNE DEFENCES

Inhibition of phagocytic killing

A

E.g. M. tuberculosis

Stops fusion of phagosome & lysosome

Results in granulomas

28
Q

What does infectious disease pathology result from?

A

Direct effects of pathogen (e.g. toxins)

Host responses (innate or specific)

29
Q

Pathological consequences of INNATE immune responses

A
  • LPS induces macrophage cytokine secretion (IL1, TNF-alpha & TLR4)
  • Systemic effects: fever, endotoxic shock
  • Possible can lead to death
  • TNF-alpha is the most potent one produced
  • Local infection contained = successful outcome
  • Systemic infection, sepsis & mass cytokine release = death
30
Q

Pathological consequences of SPECIFIC immune responses

A
  • Antibodies and/or T cell reactions may contribute to pathology
  • E.g. skin rashes in measles due to T cell response
  • E.g. granuloma formation in TB due to chronic macrophage activation
31
Q

What is ebola?

A

Filovirus: enveloped, non-segmented negative stranded RNA with filamentous particles

Causes hemorrhagic fever

Outbreak in West Africa is the largest in history
• High fatality rate: around 70% reported

32
Q

Ebola & evasion of immune responses

A
  • Infects immune cells including dendritic cells and macrophages
  • Inhibits maturation of infected dendritic cells so they do not present antigen effectively
  • Causes apoptosis leading to reduced numbers of circulating T lymphocytes and NK cells and weakened immune responses
  • Interferes with the production of type I interferon
  • Also interferes with the cellular response to interferon
33
Q

What is immunopathogenesis?

A

The process of disease development involving an immune response or components thereof

CMB2004 (12 decks)

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