L29: add more later NK, Interferons, Mucosal Immunity

Question 1

What are the characteristics of presentation/blood tests of Hyper IgM syndrome (rare)

Answer 1

Presentation is young failure to thrive, recurrent and unusual infections for age (–5yrs)

FBC
-Slightly low WBC + Neutrophils.

Serum Ig Test
-Extra high IgM, and very low IgG and no IgA.

Peripheral Lymphocytes

• B lymphocytes are IgM/ IgD (naive) only.
• Mostly T lymphocytes

Question 2

What is the mechanism of Hyper IgM syndrome (rare)

Answer 2

CD40 ligand mutation on T cells so that it cannot bind with CD40 on APC to co-stimulate it. 
Usually in the primary response this leads to T cells inducing the class switch of B cells to produce IgG/IgA or IgE instead of IgM for the secondary response, but mutation stops the class switching.

Question 3

How does the type of antibody in neonates change in utero-> 12 mo after birth

Answer 3

1. in utero maternal IgG crosses placenta reaching 80% of adult levels at birth after which it progressively drops low at 2mo, gone by 8mo.
2. After Birth baby’s IgG increases sharply as dominant Ab by 3 mo, reaching 80% of adults by 12 mo
3. IgM increases slowly up to 75% of adults by 12 mo, still not as much as conc as IgG
4. IgA from mother tops makes 20% of adult levels by 12 mo, just a top up.

Question 4

What are the 2 factors which affect immune response

Answer 4

1. Microbial factors
   - type of organism, amount, route of entry and virulence
2. Host factors:
   - innate barrier and adaptive immune competence,
   - HLA, TCR and Ig genes,
   - Previous exposure and other concurrent infections

Question 5

What is effective against extracellular antigens vs intracellular protein antigens and give examples of pathogens

Answer 5

1. Intracellular: Cytotoxic T cells
   eg. Virus infected cells, tumour, transplanted organs,

2. Extracellular: 
Antibodies 
- classical complement 
-reduce mobility
-opsonisation

eg. Viruses outside, toxins, extracellular bacteria, parasites

Question 6

What is X-linked agammaglobulinaemia and how does it present,

Answer 6

Inability to make antibodies, failure to thrive,

Presents

• Recurrent bacterial infections
• Deficient in all antibodies
• Few B cells and no Tonsils

Question 7

Describe the process of mucosal immunity against bacteria , including which antibody,

Answer 7

1. Plasma cells from peyers patches produce IgA–> external body fluids to block adherence of pathogen on epithelial cells and opsonise
2. Mast cells in submucosal regions have their IgE cross-linked by pathogen binding to it
3. Releases vasoactive and chemotactic factors into blood vessels
4. Triggers Neutrophils, and eosinophils to come.
   subsequent complement activation, and IgG production -> local inflammation

Question 8

How do bacteria avoid antibody effects

Answer 8

Have capsule which resists opsonisation eg. hib

Have intracellular growth eg. Tb

Question 9

What cells undergo antibody dependent cytotoxic killing, what do they kill and how do they kill (2 ways)

Answer 9

Killer/ Natural killer cells - large granular leukocytes that don’t require antibody priming.
- Kill infected cells (intracellular pathogens)

1. They bind antibodies with Fcy receptor and release short range killing factors
2. Natural killing of tumour/infected cells that downregulate their HLA 1 as this normally binds into the killing inhib receptor, and if not there, the signal from killer activating receptor which binds to ubiquitous carb on most cell surfaces will not be suppressed leading to kiling

Question 10

What is the time line of stuff that responds in acute viral infections

Answer 10

Early

1. Interferons which promote
2. NK/K activity
3. Cytotoxic T cells have been generated against the viral peptide presented
4. Antibodies from B cell activation which protect against re-infection (not rlly helping in initial infection).

Question 11

What is the function of interferons (cytokine) - from two sources

Answer 11

1. IFN-a&B are produced by virus infected cells and act on
   a) uninfected cells to induce transient anti-viral state by inducing specific enzymes within the cell to cleave viral RNA
2. IFN-y (+ IL2) produced by CD4 T cells stimulates NK cell activity first
   and later
   up-regulates HLA to enhance lysis by Cytotoxic T cells.

Question 12

What are the pro-inflammatory cytokines, who produces it and what are their effects

Answer 12

IL-1. IL6,
- TNF-a triggered by gram- bacteria LPS.
Produced by APC

Help to

• Induce acute phase response: change in plasma protein composition
• Act on hypothalamus–> fever and behaviour changes
• Promote tissue repair in inflammation, leukocyte adhesion
• T and B cell activation