Lecture 11 - Immunology of Infectious Diseases Flashcards
Summarise the innate immune (first line of defense) mechanisms that deal with infections
Innate - first line of defense
• Mechanical barriers
- intact mucous membrane
- intact skin
• Normal flora
- creates competition
• Secretions
- Acid in gastric juice
- Lysozyme in tears, nasal secretions and saliva
- Mucus in digestive and respiratory tracts
- Sebum (oil) pH 5
Summarise the adaptive immune mechanisms that deal with intracellular infections
- Infection of host cell (viruses, some bacteria and parasites)
- Host cell presents antigen to surface via MHC-1
- APC take up antigen and present to TH1 cells which stimulate Tc
• Cytotoxic T cells (Tc) recognize antigen in
association with MHC-1 and kill infected cell
Which infections are dealt with by the humoral branch of the adaptive
immune system? Give examples.
- Humoral: primary/initial response to an antigen
- Primary response has a lag of several days while B cells proliferate (time for invader to do harm)
- Antibody levels peaks and falls as antigen is removed
- The type of antibody is IgM (Immunoglobulin M)
Why is the MHC so important?
• The MHC is important in adaptive immunity
– MHC class II
• Presents Ag to T cell help
• Critical for CMI stimulation and production of high
affinity antibodies (IgA, IgG and IgE)
– MHC class I • Cells present Ag to Cytotoxic T cells which destroy cells • Critical for internal infections (viruses) and cancer • NK cell recognise reduced MHC class 1 to destroy cells
List the ways in which HPV evades the immune system
– HPV does not cause any major cellular damage (no innate response, no inflammation)
– HPV only infects basal epithelial cells
– HPV only produces non-secretary proteins at low levels
– No Viraemia
– Infected cells not lysed
– Limited production of antigen for systemic presentation
– Avoids Cytotoxic T cells (CD8) (E5 product inhibits transportation of MHC class 1 to cell surface, E7 interrupts production of MHC class 1)
What are the flaviviruses evasion strategies?
• Some pathogens (mostly viruses) can change (Appears to the immune system as new pathogen, immune system has to start again as a primary response)
Explain antigenic drift and antigenic shift as methods of immune evasion. Which pathogen utilises these strategies?
• Antigenic Drift :
- Small changes in the structure of haemagglutinin and neuraminidase proteins of influenza
- Can be due to host immune mutants (every 2-3 years)
- Types A and B
• Antigenic Shift:
- Large changes in the structure of haemagglutinin and neuraminidase proteins of influenza
- Can be due to recombination of virus between animal and human types
- Type A
- Influenza utilises these strategies
Neutralising antibodies are produced against HIV but they don’t work. Why?
- Some epitopes must be conserved in gp120 to bind to CD4
- However, gp120 is highly glycosylated (Long stretches of sugar molecules coat surface)
- Mutations occurred in N-linked glycosylation sites
• These changed the position of stretches of sugar (shielding the epitope)
– Preventing antibody attachment
– But allowing receptor binding
• CD4 cells becomes infected
How does a superantigen stimulate many T cells?
- Certain bacterial toxins and viral proteins stimulate all T cells that express Vβ T cell receptor (TCR) and α chain of MHC class II
- Bind to both TCR and MHC class II but not binding clefts
- Activates a large number of T cells (5 – 30%) leading to release of large amounts of cytokines
Explain “antibody dependant enhancement ADE” and what pathogen utilises this?
- Antibodies from the first infection bind but do not neutralise second infection (low affinity)
- Monocytes have Fc receptors and pick up virus via antibodies and disseminate through body – enhancing infection
- Vaccine development is a problem
- Utilised by dengue haemorrhagic fever
List three immune evasion strategies by Staphlococcus aureus.
- Coagulase positive (Produce coagulase to form clots and aggregates of cocci to protect from immune system)
- Production of toxins (This is a superantigen which leads to a cytokine storm)
- Slime (Inhibits neutrophil chemotaxis and phagocytosis)
How is the immune response in TB used as a laboratory test for TB?
• Infection taken up by mononuclear phagocytes, present to T cells – Th1 response (INF-ɣ, TNF, IL-2)
– leading to Cytotoxic T cells (CMI)
• Th1 activates macrophages
– Large amounts of INF-ɣ produced
- INF-ɣ Assay for TB
How does TB for a tubercle?
• Bacteria can survive in Macrophages – Inhibiting macrophage activation – Capsule (toxic) – Inhibits phagosome formation – Invades cytoplasm avoids phagosome – Most remain dormant
• Damage to tissue via immune response
– Recruitment of immune cells by cytokines
– Formation of tubercles (macrophages, T cells, bacteria)
– Liquefaction of tubercule causes spread of bacteria leading to more immune response
Why are RBCs good cells for malaria parasites to hide in?
- Because RBCs do not express MHC, makes it easier to evade immune system
What is molecular mimicry?
• Cross reactivity with microbial antigen
– T cell or antibody directed against a microbe antigen also reacts
against self antigen
– Epitopes highly homologous
• Microbe invades which leads to an immune response
– Homologous epitopes between microbe protein and protein on self tissue
– Immune response also directed against self
– Leads to autoimmune disease
• Demonstrated in Rheumatic fever
