Antibodies

Question 1

Antibodies

Answer 1

1. Polyclonal - same antigen specificity, different epitope specificity
   * form from diff B cells
   * vaccines
2. Monoclonal- recognizes one epitope
   * pharmacologics- easiest way to reg immune system
   * one type of B cells

Question 2

Immunoglobulins (antibodies)

Answer 2

Proteins used to neutralize pathogens

Fxns:

1. Specifically bind to pathogen/products
2. Recruit cells to kill pathogens

Question 3

Serology

Answer 3

ID of antibodies against specific antigens w/in blood

Questions is can answer:

1. Vaccination status- BUT can’t distinguish between infected and vaccinated
2. Distinguish closely related pathogens
3. ID specific pathogen
4. ID non-infectious disease

Question 4

Basic Ig structure

Answer 4

1. Variable region
2. Flexible hinge region
3. Constant region

Question 5

Variable region of Ig

Answer 5

Determines which antigens recognized

• antigen binding sites (2)
• Light and heavy chains
• noncovalent bonds to conformational epitopes

Question 6

Flexible hinge region of Ig

Answer 6

Enables one antibody to bind two small antigens or one larger (identical) antigen at a time

Question 7

Constant region of Ig (Fc effector)

Answer 7

Can bind to Fc Receptors on our cells and anchor antibodies

• doesn’t bind antigens
• forces phagocytosis and presentation
• light and heavy chains

Question 8

Antigens recognized

Answer 8

1. Immunogens
2. Haptens (w/ carriers)
3. Tolerogens
4. Autoantigens- self-antigens

Question 9

Factor affection strength of response

Answer 9

1. T cell help - cytokines boost response
2. Location
   * blood > tissue because easier to detect
   * extra cellular > intracellular => not great for fighting viruses
3. Protein > non-protein

Question 10

Antibody DNA rearrangement

Answer 10

Allows for antibody diversity

• T and B cells
• segments that make up variable region:
  1. Variable
  2. Diversity
  3. Joining
• light chain (VL) = V +J
• heavy chain (VH) = V + D + J
• rearrange first
• regulated by RAG (recombination activity gene)

10^11 possible receptors

Question 11

Valence

Answer 11

Number of binding sites

**2 per antibody

Question 12

Affinity

Answer 12

Strength of binding at single site

Question 13

Avidity

Answer 13

Total strength of all binding sites

Question 14

Ommen Syndrome

Answer 14

RAG deficiency (partially active)

• very few B and T cells because of constant infection
• very little variation in antibodies
• some pts. Might survive, but will be very sick
• presentation:
  1. Failure to thrive
  2. Erythroderma
  3. Diarrhea
  4. Severe immunodeficiency

Question 15

Severe combined immunodeficiency (SCID)

Answer 15

No RAG activity

• No B or T cells
• Fatal
• Presentation:
  1. Insterstitial lung disease
  2. Diarrhea
  3. Failure to thrive
  4. Severe recurrent infection

Question 16

Ig Isotypes (constant region)

Answer 16

Determine antibody fxn

• determined by heavy chains:
  1. IgM (mu)
  2. IgD (delta)
  3. IgG (gamma)
  4. IgA (alpha)
  5. IgE (epsilon)

Question 17

B Cell Receptor

Answer 17

Membrane- bound antibody
*Memory B cells express any isotope as BCR
*IgM and IgD both expressed on naive B cells
*Fxns:
1. Recognize and bind antigens
2 signal -> B cell activation
3. Activation:
* clonal expansion
* antibody production (plasma cells)
Alternative mRNA processing determines anchored vs. secreted

Question 18

Fxn of secreted antibodies

Answer 18

Isotope dependent
Provide specificity for innate immune system
1. Neutralization - bind/stop antigens before reach target
2. Classical complement activation - one pentameter !gM or 2 monomers IgG
3. Opsonization- IgG
4. Antibody- dependent cellular cytotoxicity (ADCC)
5. Degranulation

Question 19

Neutralization

Answer 19

Bind/stop antigens before reach target

• IgG- blood/tissues
• Dimeric IgA - mucosal surfaces
• Behring (1901) - “serum therapy” against diphtheria

Question 20

Opsonization

Answer 20

Coating outside antigen, makes more appealing to immune system

• Fc receptors -> inc. phagocytosis
• IgG

Question 21

Antibody-dependent cellular cytotoxicity (ADCC)

Answer 21

Fight viruses

*cells present viruses -> bind Fc on NK cells -> NK kill cells

Question 22

Degranulation

Answer 22

1. Mast cells - allergies
   * IgE and Fc bind, cross-linked by antigen -> histamine release
2. Eosinophils
   * IgE opsonize parasite -> eosinophils bind IgE coating w/ Fc receptors -> degranulation -> fragmentation -> phagocytosis

Question 23

IgM

Answer 23

• Secreted pentamer
• Membrane bound monomer - first Ab formed in primary response
• Can activate classical complement
• valence = 10 => high avidity
• pentamer crosses epithelium because of J chain

Question 24

X-Linked Hyper IgM syndrome

Answer 24

XS IgM

• decrease of isotypes
• life expectancy <30 years
• Presentation:
  1. Children
  2. Recurrent respiratory infections
  3. Usually pneumocystis jirovecii (uncommon)

Question 25

IgD

Answer 25

* Monomer * Barely detectable * On naive B cells with IgM * Fxn unknown, but more in respiratory tract than GI

Question 26

IgG

Answer 26

* Monomer * ~80% of serum Ab * Late primary and memory responses * crosses placenta * subclasses (IgG 1-4) - IgG1 -opsonization - IgG3 - complement activation * Fxns: 1. Neutralization 2. Opsonization 3. Complement activation 4. ADCC (NK cells)

Question 27

IgE

Answer 27

* allergies and parasites * monomer * Late primary and memory response * Penicillin allergy- hapten binds to self-protein immunogen -> IgE against hapten - cross-reacts w/ other antibotics

Question 28

IgA

Answer 28

* monomer in blood * dimer in secretions and mucous * predominant class in secretion/mucosal surfaces * saliva, tears, breast milk * easy transport thru epithelium * late primary and memory response

Question 29

Infections associated w/ antibody deficiencies

Answer 29

1. Recurrent Phoenix infections w/ extra cellular pathogens 2. Encapsulated bacteria * could indicate decreased spleen fxn 3. Recurrent respiratory infections * IgA 4. Enteritis * Giardia lamblia * IgA

Question 30

Ways pathogens evade antibodies

Answer 30

1. Antigenic variation- mutate surface epitopes to escape 2. Encapsulation - hide surface antigens w/in capsule * hard to phagocytize

Question 31

Immunodiagnostics

Answer 31

* purified antigens used to capture antibodies - check for vaccination/exposure * antibodies used to catch antigens - pregnancy hormone stick test - rapid diagnostic stick test

Question 32

Antibody titer

Answer 32

Measures how much antibody for specific antigen you have * titer = degree to which serum can be diluted and still have detectable level of antibody * reported numer is inverse of last dilution w/ detectable antibodies

Question 33

Immunoglobin superfamily

Answer 33

Includes immunoglobins, adhesion molecules, and receptors