Lecture 17+18+DLA Flashcards
lactoferrin
anti-microbial
iron-binding protein that competes with
pathogens for iron, an essential metabolite
C-reactive protein (CRP)
Acute-phase protein that binds to phosphocholine in bacteria membranes and function in opsonization.
It activates complement via the classic pathway
Mannose-binding lectin (MBL)
MBL recognizes carbohydrate patterns, found on bacteria, viruses, protozoa, and fungi, resulting in activation of the lectin pathway of the complement system
Serum amyloid A protein (SAP)
binds to bacterial cell wall lipopolysaccharide and serves as a receptor for phagocyte attachment.
Implicated in several chronic inflammatory diseases, such as amyloidosis, atherosclerosis, and rheumatoid arthritis
serum amyloid A protein
interferon
a small protein that is produced by certain WBC’s and virally infected cells
produced in response to viruses, RNA, immune products, and antigens
Interferon alpha and Interferon beta (Type I)
Type I interferons can be produced by almost any cell upon stimulation by a virus
Act on neighboring uninfected cells
Inhibit transcription and translation of viral proteins
Interferon gamma (Type II)
Produced by: Th1, CTLs (CD8+), NK cells
promotes NK cell activity
increases the activity of macrophages
Activates inducible nitric oxide synthase (iNOS):
relaxes smooth muscle, vasodilation
induces the production of ab’s
normal cells will expresses MHC I + II after interaction
promoted adhesion and binding required for leukocyte migration
respond to cancer growth
will lead to the transcription of antiviral effects
granuloma
the bodies mechanism to deal with a substance that cannot be removed
infectious causes:
TB, leprosy, histoplasmosis, ect.
non-infectious causes: crohn’s disease
IFN (gamma) and granulomas
Association between IFNγ and granulomas: IFNγ
activates macrophages to kill intracellular organisms
activation of th1 helper cells by the macrophages
IL-1 and IL-12 by macrophages
Th1 helper cells aggregate around the macrophages
then IFN gamma activates the macrophages
macrophages surround the Th1 helper cells and
become fibroblast-like cells walling off the infection
The complement system
serum glycoproteins synthesized principally by hepatocytes, but also monocytes, macrophages, and epithelial cells
recruitment of inflammatory cells and the killing or opsonization of pathogens
Complement proteins are activated by cleavage (cascade reaction)
inactive precursors in blood: C2, C3, C4
C1 through C9
The classical pathway
adaptive immunity
- C1 bind to Ag-Ab complex
- activated C1 cleaves C4 and C2
- formation of C3 convertase
- C3 and C5 are cleaved
- sequential binding of C5b, C6-C9
The alternate pathway
innate immunity
Spontaneous cleavage of C3 based on multiple
initiators
requires factors B and D
formation of a less stable C3 convertase
needs properdin
MBL pathway
innate immunity
Mannan-binding lectin (MBL), an acute phase
protein found in serum binds to carbohydrate residues on cells or pathogen surfaces
MASP binds to MBL
MASP = MBL associated serine protein
this complex cleaves C4 and C2
MAC
the Three pathways converge with activation of C5
convertase
C5b binds antigenic surface
MAC is formed on surface
C5Components:
C5b,C6, C7, C8, C9
Poly -C9: perforin-like molecule
role of C5b - C9
cell lysis
opsonization
C3b
role of C3a and C5a
INF
role of C3b, C5b-C9
viral neutralization
Inhibit C1
C1 inhibitor
classical pathway
Deficiency results in angioedema (hereditary or
acquired)
Prevent assembly of C3 convertase
CR1 (CD35)
MCP (CD46)
C4b binding protein
factor H
Accelerate decay of C3 convertase
DAF (CD55)
Block MAC
CD59 (protectin), S protein, clusterin
Inactivates anaphylatoxin C3a and C5a
Anaphylatoxin inactivator
Activator disorders: complement deficiency
under-reactive system. More susceptible to
infections
inhibitor disorders: complement deficiency
overreactive system
Classical pathway component deficiencies (C1, C4, C2)
more prone to immune complex disease
inability to clear circulating immune complexes
deposition into tissues
EX: Systemic Lupus Erythematosus (SLE),
Glomerulonephritis, Vasculitis
MBL deficiency
Classically presents with recurrent pyogenic infection in childhood
Susceptibility to Saccharomyces cerevisiae, pneumococcal and Neisseria infections
can be auto dom or recessive
Alternative pathway component deficiencies (Properdin, factor B and factor D)
Affected individuals are prone to pneumococcal and
meningococcal infections
Properdin deficiency: risk of overwhelming Neisseria infection
C3 deficiency
C3 is required for opsonization
Primary C3 deficiency tends to present in early life with
overwhelming infection with encapsulated organisms
connective tissue diseases
MAC deficiencies (C5-C9)
Recurrent infections
Common Infection with Neisseria meningitidis
DAF (decay accelerating factor)/CD55 and CD59 deficiency
Paroxysmal Nocturnal Hemoglobinuria (lysis of red
blood cells)
hereditary angioedema
characterized by episodic, nonpruritic, localized subcutaneous and submucosal swelling
dysregulation of three systems:
classic (C1), MLB (MASP-2)
excessive activation of the complement due to
mutation on C1inh results in high concentration
of anaphylatoxins: C3a and C5a
reduced C4 on testing
The hemolytic titration (CH50) assay
needs all complement molecules in order to work
prevalence formula
number of cases / size of the population
point prevalence
of cases / # of persons
incidence proportion
number of new cases of disease / pop. without the disease
