10 - Acquired Immunity

Question 1

Types of immunity:

Answer 1

1. Type 1; Intracellular immunity
   a) ILC1 and TH1 cells
   b) Elimination of intracellular pathogens and activation of macrophages
2. Type 2; Mucosal and barrier immunity
   a) ILC2 and TH2 cells
   b) Elimination and expulsion of parasites and recruitment of eosinophils, basophils, and mast cells
3. Type 3; Extracellular immunity
   a) ILC3 and TH17 cells
   b) Elimination of extracellular bacteria and fungi and recruitment and activation of neutrophils

Question 2

What is the innate immune response to viruses?

Answer 2

1. The initial defence against virus invasion is the anatomical barriers such as acidic pH, proteolytic enzymes, bile, and mucous layers
2. Key innate antiviral effectors include type 1 interferons (IFNs), tumour necrosis factor (TNF) alpha, defensins, natural killer cells, neutrophils, and macrophages

Question 3

Describe Type 1 Interferons:

Answer 3

1. Type 1 IFN production is triggered following recognition of molecular pattern characteristic of viral infection
   a) The interferons act on both the cells producing it and neighbouring cells
2. Interferons act on cells to produce an antiviral state, for example:
   a) Interferon-induced transmembrane proteins inhibit the entry of a number of viruses into cells
   b) MX proteins block early steps of the viral replication cycle
   c) Tetherin inhibits the release of enveloped viruses from infected cells
3. IFNs also activate NK cells and enhance their antiviral activity
   a) Activated NK cells observed within 2 days of viral infection
4. IFNs also stimulate macrophages

Question 4

What do antibodies do in viral infections?

Answer 4

1. Restrict virus from spreading in the blood stream, thereby limiting spread of virus throughout body
   a) This can be done by blocking binding to cell

Question 5

What do T cells do in viral infections?

Answer 5

1. Important effector cell that play a key role in the control of established viral infections
2. Most antibody response is T-cell dependent
3. CD4+ T cells help in the induction of CD8+ T cell responses and in the recruitment and activation of macrophages at sites of viral infection
4. Memory CD8+ T cells are effective in combatting re-infection with viruses such as influenza virus and respiratory syncytial virus
5. CD8+ cells:
   a) Kill infected cells
   b) Trigger apoptosis (cell suicide) of infected cells

Question 6

How do viruses evade the immune response?

Answer 6

1. Impair the host response
   a) Viruses can block type 1 IFN production
   b) Some viruses can impair the recruitment of dendritic cells to sites of infection
   c) Viruses can disrupt the chemokine network
2. Avoid recognition by the host immune defence
   a) Latency
   b) Infection of immune privileged sites
   c) Rendering infected cells less visible to host effector cells
   d) Antigenic variation
   e) MHC class I expression disruption
3. Resist control by immune effector mechanisms

Question 7

What are some pathological consequences of immune responses induced by viral infections?

Answer 7

1. Excessive cytokine production and immune activation can cause cytokine storms (e.g. SARS)
2. Poorly neutralising antibodies can enhance viral infectivity (antibody-dependent enhancement of viral infection - e.g. Dengue)
3. Antiviral antibodies can form immune complexes that cause tissue damage (e.g. glomerulonephritis)
4. Virus-specific T cell responses can cause severe tissue damage (e.g. killing important self tissue)
5. Viral infection may provoke autoimmunity (e.g. molecular mimicry in Cosackie B virus and Diabetes)

Question 8

What are the four major categories of human fungal infections?

Answer 8

1. Superficial mycoses
   a) Caused by fungi known as dermatophytes which are usually restricted to the non-living keratinised components of skin, hair, and nails
2. Subcutaneous mycoses
   a) Result of introduction by local trauma of saprophytic fungi which can cause chronic nodules or ulcers in subcutaneous tissues and may lead to osteomyelitis
3. Systemic mycoses which are opportunistic infections following loss of cell-mediated immune functions
4. Candidiasis caused by Candida albicans which is the most common opportunistic fungal pathogen

Question 9

What are the innate immune responses to fungi?

Answer 9

1. The basic protective features of the skin and normal commensal flora against bacteria infections
2. Defensins have antifungal as well as antibacterial properties
3. Collectins such as MBL and the surfactant proteins A and D can bind, aggregate, and opsonise fungi for phagocytosis
4. Phagocytes, particularly neutrophils and macrophages, are essential for killing fungi by either:
   a) Degranulation and release of toxic materials onto large indigestible hyphae
   b) Ingestion of yeast of conidia
   c) These killing responses rely on the recognition of PAMPs in the fungal cell wall

Question 10

What are the adaptive immune responses to fungi?

Answer 10

1. Cell-mediated immunity is the major mechanism of adaptive immunity against intracellular fungal infections
2. Th1 responses are protective in intracellular fungal infections
3. Fungi also elicit specific antibody responses that may be of protective value

Question 11

How does fungi evade the human immune response?

Answer 11

1. Neoformans produce a polysaccharide capsule which inhibits phagocytosis
2. Candida can conceal the beta-glucans of their cell wall which would otherwise be recognised by the immune system
3. H. capsulatum can evade macrophage killing by entering the cell via CR3 and then altering the normal pathways of phagosome maturation
4. Dermatophytes suppress host T-cell responses to delay cell-mediated destruction

Question 12

What is the innate immune response against parasitic infection?

Answer 12

1. First line of immune defence

Question 13

What is the adaptive immune response against parasitic infection?

Answer 13

1. Both CD4 and CD8 T cells are needed for protection against parasites
   a) T-cell responses to protozoa depend on the species
2. B cells are also pivotal in the development of immunity
3. Effector cells such as macrophages, neutrophils, eosinophils and platelets can kill both protozoa and worms
   a) All are more effective when activated by cytokines

Question 14

Describe antigen presentation against bacteria:

Answer 14

1. Macrophage takes in bacteria and presents antigen to T cell
   a) If bacteria has not infected cell then helper T cell us activated which activates B cells which stimulate B cell production to break down bacteria - most common
   b) If cell is infected then cytotoxic T cells which causes destruction of bacteria by cell lysis (destruction)

Question 15

What are the 2 ways to activate B-cells in bacterial infections?

Answer 15

1. Phagocyte (APC) engulfs bacteria and presents antigen to helper T cell via MHC class II
2. Antigen attaches to antibodies on surface of B-cells that have already been activated