Defenses and Deficiencies Flashcards
What is the innate immune system?
A branch of the immune system that is always ready to react and eliminate pathogens. Does not need prior exposure to pathogen.
What are some key features of the innate immune system?
Causes inflammation, antiviral defense, stereotypical response, Recognizes ‘foreign vs self’
What are the physical barriers that pathogens encounter?
Tight junctions (endo/epithelial cells), Mucous (contain antiboitics), Cilia, Gut peristalsis, Other normal microbiota
What are the chemical barriers that pathogens encounter?
Acidic pH, Antimicrobial peptides, Lysozyme, Lactoferrin, Apolactoferrin, Surfactants and Antibodies.
Where is acidic pH in the body?
Skin, stomach, urine, vagina and bile.
What types of antimicrobial peptides are present?
Defensins and cathelicidins; Toxic to microbes and recruits leukocytes.
What does lysozyme do?
Hydrolyses peptidoglycan in bacterial cell walls; Produced by epithelial cells of mucous membranes. Also found in lysosomes of phagocytes.
What does lactoferrin do?
Binds free iron to inhibit bacterial growth; Found in same locations as lysozyme.
What is apolactoferrin?
Blocks viral entry by binding lipoproteins, a viral attachment receptor, on epithelial cells.
What do surfactants do?
Bind DIRECTLY to bacteria, viruses, and fungi to increase their phagocytosis; Made by respiratory epithelium, concentrated in alveoli.
What role do antibodies play?
Lead to destruction of microbes through multiple mechanisms; Made by B cells, Located in serum, tears, mucus and breast milk.
What produces plasma proteins?
Constitutively produced by hepatocytes.
What are the three types of plasma proteins? What function do they share?
Acute phase reactants, Mannose binding lectin and complement proteins. They are all opsonins.
What do acute phase reactants do?
They bind to bacterial membranes and apoptotic cells to opsonize them and activate complement cascade. C-reactive proteins(CRP) and serum amyloid P (SAP)
What danger does too many circulating Acute phase reactans present?
Increased risk of heart attack.
What does mannose binding lectin do?
Opsonizes and activates complement. Bind to SURFACE of pathogens.
What do complement proteins do?
Opsonize, recruit phagocytic cells, and lyse by binding directly or indirectly to target surface.
What are the pathways of complement protein?
Alternative, classical and lectin pathways.
Describe the alternative pathway activation.
- C3 is cleaved into C3a and C3b in the serum
2. C3b is bound to pathogen; C3a is an anaphlatoxin (attracts leukocytes)
Describe the classical pathway activation.
- Antibody (IgG or IgM) or CRP/SAP binds to the pathogen’s surface antigen.
- C1 is recruited & and then recruits C4 and C2.
Describe the lectin pathway activation.
- Mannose is the surface antigen.
2. Mannose binding lectin binds mannose, then recruits C2 and C4.
Describe the classical and Lectin pathways once C4 is recruited.
- C4 and C2 are split into C4a, C4b, C2a and C2b.
2 C4b and C2a combine to make and enzyme (C3 convertase). - C3 convertase cleaves C3 into C3a and C3b.
Describe the post activation sequence in the alternative pathway.
- Factor B is cleaved into Bb and Ba.
2. Bb combines with C3b to make C3 convertase.
Why is the cleavage of C3 so important?
C3a is an anaphlatoxin; binds to mast cells, neutrophils and macrophages. C3b is the most powerful opsonin.
Once C3b is bound, what are the 2 things that could happen?
Option 1: Phagocyte recognizes C3b using C3b receptor and engulfs the microbe.
Option 2: C3a, C4a or C5a are anaphlatoxins that bind to neutrophils; Neutrophils kill bacteria.
How does C3 convertase in the alternative pathway act as a positive feedback loop?
C3 convertase makes C3b. C3b can make more C3 convertases.
What else can C3b do?
It is a component of C5 convertase in all pathways; Further cleavage of C3b produces C3d. C3d induces B cell differentiation.
When is C5 convertase made?
When C3 convertase is not enough to clear the infection; It cleaves C5 into C5a and C5b.
What are the functions of C5a and C5b?
C5a does the same job of C3a. C5b binds covalently to the surface of the pathogen; Initiates the steps to make the MAC by recruting C6,7,8,and 9.
What if the MAC is not enough?
Extracellular pathogens are phagocytosed by macrophages, dendritic cells and neutro/eosinophils.
Intracellular pathogens are eliminated by NK cells or cytokines that make the cell unfavorable for reproduction.
Describe a C3 defect.
Results in recurring infections and is often fatal; Most severe defect.
Describe C2 or C4 defect.
Most common deficiency; Increased pyogenic, viral infections with increased chanc of lupus.
Describe C5 or later defects.
Inability to form the MAC; Increased risk to infection by Neisseria bacteria
