Defenses and Deficiencies

Question 1

What is the innate immune system?

Answer 1

A branch of the immune system that is always ready to react and eliminate pathogens. Does not need prior exposure to pathogen.

Question 2

What are some key features of the innate immune system?

Answer 2

Causes inflammation, antiviral defense, stereotypical response, Recognizes ‘foreign vs self’

Question 3

What are the physical barriers that pathogens encounter?

Answer 3

Tight junctions (endo/epithelial cells), Mucous (contain antiboitics), Cilia, Gut peristalsis, Other normal microbiota

Question 4

What are the chemical barriers that pathogens encounter?

Answer 4

Acidic pH, Antimicrobial peptides, Lysozyme, Lactoferrin, Apolactoferrin, Surfactants and Antibodies.

Question 5

Where is acidic pH in the body?

Answer 5

Skin, stomach, urine, vagina and bile.

Question 6

What types of antimicrobial peptides are present?

Answer 6

Defensins and cathelicidins; Toxic to microbes and recruits leukocytes.

Question 7

What does lysozyme do?

Answer 7

Hydrolyses peptidoglycan in bacterial cell walls; Produced by epithelial cells of mucous membranes. Also found in lysosomes of phagocytes.

Question 8

What does lactoferrin do?

Answer 8

Binds free iron to inhibit bacterial growth; Found in same locations as lysozyme.

Question 9

What is apolactoferrin?

Answer 9

Blocks viral entry by binding lipoproteins, a viral attachment receptor, on epithelial cells.

Question 10

What do surfactants do?

Answer 10

Bind DIRECTLY to bacteria, viruses, and fungi to increase their phagocytosis; Made by respiratory epithelium, concentrated in alveoli.

Question 11

What role do antibodies play?

Answer 11

Lead to destruction of microbes through multiple mechanisms; Made by B cells, Located in serum, tears, mucus and breast milk.

Question 12

What produces plasma proteins?

Answer 12

Constitutively produced by hepatocytes.

Question 13

What are the three types of plasma proteins? What function do they share?

Answer 13

Acute phase reactants, Mannose binding lectin and complement proteins. They are all opsonins.

Question 14

What do acute phase reactants do?

Answer 14

They bind to bacterial membranes and apoptotic cells to opsonize them and activate complement cascade. C-reactive proteins(CRP) and serum amyloid P (SAP)

Question 15

What danger does too many circulating Acute phase reactans present?

Answer 15

Increased risk of heart attack.

Question 16

What does mannose binding lectin do?

Answer 16

Opsonizes and activates complement. Bind to SURFACE of pathogens.

Question 17

What do complement proteins do?

Answer 17

Opsonize, recruit phagocytic cells, and lyse by binding directly or indirectly to target surface.

Question 18

What are the pathways of complement protein?

Answer 18

Alternative, classical and lectin pathways.

Question 19

Describe the alternative pathway activation.

Answer 19

1. C3 is cleaved into C3a and C3b in the serum

2. C3b is bound to pathogen; C3a is an anaphlatoxin (attracts leukocytes)

Question 20

Describe the classical pathway activation.

Answer 20

1. Antibody (IgG or IgM) or CRP/SAP binds to the pathogen’s surface antigen.
2. C1 is recruited & and then recruits C4 and C2.

Question 21

Describe the lectin pathway activation.

Answer 21

1. Mannose is the surface antigen.

2. Mannose binding lectin binds mannose, then recruits C2 and C4.

Question 22

Describe the classical and Lectin pathways once C4 is recruited.

Answer 22

1. C4 and C2 are split into C4a, C4b, C2a and C2b.
   2 C4b and C2a combine to make and enzyme (C3 convertase).
2. C3 convertase cleaves C3 into C3a and C3b.

Question 23

Describe the post activation sequence in the alternative pathway.

Answer 23

1. Factor B is cleaved into Bb and Ba.

2. Bb combines with C3b to make C3 convertase.

Question 24

Why is the cleavage of C3 so important?

Answer 24

C3a is an anaphlatoxin; binds to mast cells, neutrophils and macrophages. C3b is the most powerful opsonin.

Question 25

Once C3b is bound, what are the 2 things that could happen?

Answer 25

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.

Question 26

How does C3 convertase in the alternative pathway act as a positive feedback loop?

Answer 26

C3 convertase makes C3b. C3b can make more C3 convertases.

Question 27

What else can C3b do?

Answer 27

It is a component of C5 convertase in all pathways; Further cleavage of C3b produces C3d. C3d induces B cell differentiation.

Question 28

When is C5 convertase made?

Answer 28

When C3 convertase is not enough to clear the infection; It cleaves C5 into C5a and C5b.

Question 29

What are the functions of C5a and C5b?

Answer 29

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.

Question 30

What if the MAC is not enough?

Answer 30

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.

Question 31

Describe a C3 defect.

Answer 31

Results in recurring infections and is often fatal; Most severe defect.

Question 32

Describe C2 or C4 defect.

Answer 32

Most common deficiency; Increased pyogenic, viral infections with increased chanc of lupus.

Question 33

Describe C5 or later defects.

Answer 33

Inability to form the MAC; Increased risk to infection by Neisseria bacteria