Innate Immunity Flashcards
which part of the immune system is non specific and fast acting? which ones are specific with memory?
5Is for the innate immune system
- instant
- immediate
- initial repsonse
- induces adaptive response
- integrates wiht adaptive
5As for adaptive
- acquired
- await days
- accurate
- autoregulated
- autoimmunity
which cellular components comprise the innate immune systems
complement systems
- phagocytes:
eosinophils, macrophages, neutrophil, monocytes, basophil
natural killer cells and dendritic cells (also phagocytic)
In the innate immune system, pathogens are recognized and various chemicals like cytokines are released to further activate the immune response and recruit other immune cells. How are the pathogens recognized? What aspects of the innate immune system recgonizes the pathogens?
microbes have tags that are recognixed. Called PAMPS. Pathogen associated molecular patterns.
Pattern recognition receptors (PRR) are on immune cells. binding of PAMP to PRR acgivates the immune response including
- opsonization
- activating the complement
- phagocytosing the pathogen
- activating inflammatory mediators (Cytokines)
- inducing apoptosis of infected cells.
How do neutrophils in the blood enter into tissues to phagocytosis bacteria?
bacteria releases substancs that signal neutrophils rolling around the blood to stick onto the endothelial cells and the diapedesis/squeeze between to phagocytose the bacteria.
neutrophil disorders can be due to neutropenia ( not enough) or malfuncition (won’t work). If the WBCsa have adhesion deficiencies, what would this be characterized as?
leukocyte adhesion deficiencies are defects in the proteins required for neutrophil adhesion to endothelium and rolling.
- the patient won’t form pus and the white cell will be high cause its not leaving through the pus.
2 major opsonins
complements (innate immunity) or immunoglobulin (humural)
opsonins coat the bacteria and aif in neutrophil adherence and ingestion. defects are usually deficinecy of complement or antibody.
• Neutrophils ingest the opsonized microorganisms by
surrounding them with moving pseudopodia, which fuse
to enclose the microbe within a vesicle called the
phagosome
• Degranulation of cytotoxic and hydrolytic enzymes into the phagosome creates the phagolysosome and kills the bacteria
chediak higashi syndrom
a complement deficiency of C3 and C5 that prevents phagocytic effects. causes albinism, easy bruising.
the granules of the neutrophils don’t release their load very well because the complement system defect prevents cell-pathogen interactions.
Corticosteroids affect which processes in the pathway of neutrophil function:
A) Increase adhesion
B) Cause a defect in chemotaxis
C) Cause a defect in phagocytosis
D) Inhibit opsonization
E) B and C only
E.
they decrease adhesion (rule out A), and its not proven that they inhibit opsonization
once phagocytosed by a neutrophil or a monocyte/macrophage, how does the actual killing of the pathogen occur?
thrgouh neutrophil oxidative killing
not shown: step 5. H2O2 reacts with superoxxide anion forming HOCl and chlorine. Causes a burst – rapid consumption of O2 and production of superoxide (O-) and its metabolites
- proteases are relased and help destroy the pathogen.
chronic granulomatous disease
problems with neutrophil oxidative killing. A defect in neutrophil oxidative killing resulting in infection
with catalase positive organisms Unable to produce superoxide radicals in phagolysosome. Due to mutations in one of 5 subunits of the NADPH
respiratory burst oxidase complex
Catalase negative organisms generate enough H within the phagolysosome to result in killing
• Die in their own “toxic waste”
CGD results in severe and recurrent staph/bacteria and fungal infections by catalase positive organisms. WBC with someone with CGD is relateively normal because this is not an adhesion or WBC deficiency problem. it’s a biochemical issue. This would be displayed on the neutrophil oxidative burst index (NOBI) test or the Dihydrorhodamine (DHR) test.
Prophylactic TMP/SMX (Septra) to prevent
Staph infections
• Prophylactic antifungals
• Usually daily itraconazole
• Bone marrow transplantation
• Gene therapy (clinical trials)
Note:
CGD can also be X linked or autosomal recessive (less evere)
3 complement pathways
- classical pathway (antibody-antigen interactions) C1, C2, C4
- lectin pathway (lectins and glc/Nac)
- alternative pathway *microbes and particles) Factor D Factor P
diagnosing a complement deficiency
• CH50/Total Hemolytic Complement
• Screen all patients with Neisseria sp.infections for
complement deficiency!
• C3 and C4 levels DO NOT rule out a complement
deficiency • If CH50 normal and high suspicion, refer to
immunology
Patients with complement deficiencies are particularly susceptible to:
• Streptococcus pneumoniae
• Neisseria meningitidis
• Neisseria gonorrhoeae
• Beta hemolytic streptococcus
Infections patients present with:
• Bacteremia
• Sepsis
• Pneumonia
Severity of illness and response to therapy is not altered but patients are at risk for repeat infections
management of complement deficiencies
• Vaccination against meningococcus,
pneumococcus
• High index of suspicion for meningococcal or
pneumococcal infection if they present with fever
• Standard therapy for infections
• Medicalert bracelet
• Management of immune complex disease
Note
