IMM: Immune Defects and Infection Flashcards
1
Q
- What is the purpose of the innate immune system?
- Name the four general categories of the innate immune system.
- Give an example of an organ with lots of innate immunity.
A
PURPOSE
- Senses pathogens in our system.
- Prepares adaptive system, and assesses the damage.
Rapid, non-specific response system. It responds the same way each time a foreign substance is encountered.
GENERAL CATEGORIES
- Physical barriers
- Skin and mucous membranes.
- Soluble proteins
- Complement molecules.
- Acute phase reactants (CRP).
- Cellular components
- Neutrophils, macrophages, NK cells.
- Cytokines = how cells communicate.
- IFN-gamma, TNFa, interleukins.
- The liver.
2
Q
What are the four steps of innate recognition of pathogens?
A
- Innate immunity senses nonself.
- Conserved structures.
- Genetically fixed in pathogens, but not in us.
- Cytokines are produced.
* Communication. - Acute phase reactants produced locally + by liver.
- CRP and complement.
- Highlighter molecules → maximises efficiency of phagocytosis and cell destruction.
- Measures to localise spread of infection and enhance systemic resistance.
3
Q
- What is the purpose of the pattern recognition receptors?
- What is the name of the patterns that they recognise?
- What are some examples?
A
- Detect the conserved structures
- Altered cells
- Oxidised cells
- Oxidised membrane structures
- Pattern on a pathogen → pathogen associated molecular patterns = PAMPs.
- LPS.
- Flagellin.
- dsRNA.
- Unmethylated CpG DNA.
4
Q
What are PAMPs?
A
Tissue damage can release normally sequestered molecules from inside cells – damage-associated molecular patterns (DAMPs).
5
Q
- Where are toll-like receptors located?
- The TLRs that recognise the bacteria components, where are they?
- What do TLRs activate? Give an example.
- What do the things activated by TLRs do?
A
- Located on the cell surface and in the walls of intracellular vesicles.
- Extracellular membrane.
- TLRs activate transcription factors, e.g. NFkB.
- NFkB induces pro-inflammatory cytokines and chemotactic factors.
- TLRs also activate IRF to induce antiviral type I interferons (IFNa and IFNb).
6
Q
- Where are the three TLRs that recognise viral components?
- Where are they?
- TLR-4 recognises what structure present on bacterial cell walls?
A
- TLR-3, 7, 9.
- Sit within the cytosol of the cell.
- Associated with damaged DNA.
- TLR-4 recognises LPS (lipopolysaccharide) from bacterial cell wall.
- Located on outside of cell wall.
7
Q
- What are NOD-like receptors?
- Give an example.
- What do they do? (+ clinical diagnosis if this NLR is altered).
- Give an example.
- Give an example of where NLRs are found?
A
- Floating, non-membrane bound intracellular sensor of infection and other molecules.
- NLR example = Cryopyrin = NALP3.
- Induces fever → Hereditary periodic fever syndrome.
- Particularly epithelial cells in the gut.
- NLR example = Cryopyrin = NALP3.
8
Q
- Describe the structure (3 individual components) and discuss the function of an inflammasome.
A
-
Structure:
- Pro-caspase-1, NLRP3 (NALP3) and ASC.
-
Function:
- Components that come together with the end result of cleaving pro-cytokines to release their active form, eg IL-1b, Il-18.
- Inflammasome creates caspase-1, which converts inactive cytokines eg prIL-1b and IL-18
Contains NLRP3.
Trigger = oxidative damage or potassium efflux.
Inflammasome activates pro-caspase 1 to caspase 1 (slide 8/41).
Caspase 1 cleaves pro-cytokines.
Examples = IL-1B and IL-18.
Clin example: Muckel-Wells
Treatment: anti-IL-1b antibody → no fever.
Untreated: amyloidosis and subsequent death.
9
Q
- Describe the role of C3, referring to C3a and C3b.
- What uniquely happens to C3b in the alternative complement pathway?
- What three factors stabilise this?
- What do factors H and I do?
- What uniquely happens to C3b in the alternative complement pathway?
- What do all three arms of the complement system converge on? (Hint: Sesame Street)
- Is elevated C3 pathogenic?
- Discuss the mechanisms of C3 depletion.
A
- C3a is a chemoattractant.
- C3b is an opsonin; marks the pathogen for phagocytosis.
- C3b is deposited directly on the microbe.
- Factors B, D and P stabilise this complex.
- Prevent C3b from binding to other things (together they displace and inactivate C3 convertase on host cells).
- C3b is deposited directly on the microbe.
- C3b.
- No, as it is often apart of the acute phase response.
- C3 depletion.
- Consumption.
- Deficiency.
- Genetic.
- Not produced eg liver disease.
- Loss.
10
Q
Discuss C5, and the role it plays in making the membrane attack complex.
A
- C5 breaks into C5a, an attractant, and C5b.
- C5b binds to C6, and then C7 binds to this complex, etc etc.
- Forms the MAC.
- MAC forms a pore into the cell, and lyses the cell.
11
Q
- Name two of the complement proteins specific to the classical pathway.
- Classical complement deficiency leads to what two phenomena?
A
- C2 and C4.
- C4b and C2a come together to make C3 convertase, which cleaves the C3 molecule.
- SLE and pyogenic infections.
12
Q
Which group is the MBL pathway important in?
A
- Childhood (6-24 months).
- May be a factor in patients with other concurrent immunodeficiencies but alone in adults, not usually significant.
13
Q
- Describe the role C3 nephritic factor plays in the alternative pathway.
A
- C3neF is an autoantibody that stabilizes the alternative pathway C3 convertase (C3bBb).
- Remember: C3 convertase is what cleaves C3 into active forms that lead to the formation of the MAC.
14
Q
CD59 (protectin) and DAF deficiency are rare complement disorders. Describe (briefly) their pathology and clinical signs.
A
- X-linked deficiency in PIG-A gene, causes lack of GPI tails on proteins.
- Complement “think” erythrocytes are bacteria, leading to red cell lysis.
- Paroxysmal = A sudden recurrence or intensification of symptoms.
- Dark urine overnight.
15
Q
Name three immune cells capable of phagocytosis.
A
- Macrophages.
- Dendritic cells.
- Granulocytes (polymorphonuclear leukocytes).
16
Q
Describe the roll and adhere mechanism of neutrophils and discuss the proteins that mediate this process.
A
- Neutrophils roll along endothelium.
- Endothelium expresses adhesion molecules.
- Inflammatory cytokines such as TNF-a are required for expression of adhesion molecules such as ICAM-1 and ICAM-2.
- Receptor on leukocytes = integrin.
- Chemokines (eg. CXCL8) upregulate the adhesion molecule ligands on neutrophil surfaces, called integrins, such as LFA-1.
20
Q
- Describe the evolution of a B cell.
- How can B cells be measured in periphery?
- B cells can be broken down into two categories: T cell dependent and independent.
- Describe the plasma cells they produce.
- Give an example of each.
- T independent B cells are produce in the ____ and recognise ______ ______ as bacteria. They mostly produce ___ antibodies.
A
- Stem cell → Pro B cell → Pre B cell → Immature B cell → Migrates from bone marrow and matures in the periphery → Evolves some more steps → Memory B cell → Plasma blast cell → Plasma cell (which produces antibodies).
- Using flow cytometry.
- T cell dependent and T cell independent; T cells assist the B cell in the production of antibodies.
- DEP’T: Long-lived plasma cells; Follicular B cells.
- INDEP’T: Short-lived plasma cells; Marginal zone B cells.
- T independent B cells are produce in the spleen and recognise sugar moieties as bacteria. They mostly produce IgM antibodies.
