5. B-CELLS & T-CELLS (IMMUNO)

(Slide #1). B-Cells: (CD19 + cells) → Selected clone w/ differenciate + divide into?

1. Plasma cells

• A. Short lived plasma cells

  • Circulating → 60% of plasma cells

  • Produce antibody, 2,000/sec

  • Role to clear CURRENT infection

• B. Long lived plasma cells

  • Return to and reside in Bone Marrow

  • Half ½ life greater than 6 months (last a while, but not entire lifetime)

  • Continuous synthesis of antibody

    • Antibody titers/vaccine effectiveness/past exposure

    • Shared w/ fetus

    • Allows for rapid antibody binding if re-infected (second exposure)

• 2. Memory B-cells for (future infections)

(Slide #1). B-Cells: (CD19 + cells) → What are the 2nd type of cells?

2. Memory B-Cells

• Require re-stimulation to differentiate and divide (to produce antibody)

  • (Into short lived PC, long lived PC and more memory cells)

• Half-life of 5 years

• Produce + secrete antibodies (or IMMUNOGLOBULINS)

  • Recognize antigens, more specifically EPITOPES (part of an antigen)

    • (Region of antigen that antibody recognizes- typically region of 5-26 AA)

    
    

    • An antigen will typically contain may epitopes where antibodies can bind

  • Idiotype - what binds to the EPITOPE/ANTIGEN

(Slide #2). B-Cells: Produce and secrete what?

• Produce + secrete antibodies (or IMMUNOGLOBULINS)

  • Recognize antigens, more specifically EPITOPES (part of an antigen)

    • (Region of antigen that antibody recognizes- typically region of 5-26 Amino Acids)

    
    

    • An antigen will typically contain many EPITOPES where antibodies can bind

      • Idiotype - what binds to the EPITOPE/ANTIGEN

B-CELLS: ANTIBODIES/ IMMUNOGLOBULINS

• ISOTYPE region → (a more constant region, Fc)), → what can stick to more different type (NOT binding to antigens)

  • → ( Class of antibodies = 5 Types

  • → Ex: IgG, IgM, IgE, IgA, IgD) → they come from Short-lived plasma cells (Dr. L)

• IDIOTYPE region (variable, Fab)

• Region for antigen recognition 10^9 different types (for different antigens)

• FUNCTION:

  • 1. Opsonization

  • 2. Neutralization (takes a lot of antibodies to do this)

  • 3. Aggregation/agglutination

  • 4. Complement activation

• EX: (Dr. L) → Coughing only on the mucosal surface area, killing → will have isotype like IgA -= musical antibody or if its something in my bloodstream → will actually produce IgG or IgM

• Systemic = when a pt goes into sepsis (multi-organ failure)

B-CELLS: What are the types of ANTIBODY ISOTYPES?

• IgM:

  • Antibody produced following FIRST EXPOSURE to antigen (pathogen)

  • Circulating (blood, extracellular fluid)

  • Also bonds to surface of B-cell (B-cell receptor)

    • (Higher on immature B-cells)

  • Pentameter

• IgG:

  • Antibody produced by memory cells (that become short-lived plasma cells) → during FUTURE EXPOSURES to same antigen → lives in BONE MARROW

  
  

  • Circulatory (blood, extracellular fluid)

  • Produced by long-lived plasma cells (long-term antibody titers)

  • 75% of antibodies in blood

  • Can cross the placenta (99% of antibodies in infant after birth, last 6 months)

    • Four classes: IgG1 for proteins, IgG2 for polysaccharides, IgG3 for proteins, IgG4 for food allergens)

B-CELLS: What are the types of ANTIBODY ISOTYPES?

• IgA:

  • Secretory Antibody

    • Targets mucous membranes, breast milk Dimer:

      • Breast milk: 1% of antibodies in infant (what mother is currently exposed to)

• IgE:

  • Binds to basophils/mast cells to increase specificity for future infections → involved in allergies

  
  

  • Can bind to parasites → targeting them for eosinophil recognition (antibody dependent cellular toxicity (ADCC))

• Babies are born with antibodies, but they don’t replicate

B-CELLS: What are the types of ANTIBODY ISOTYPES?

• IgD:

  • B-cell receptor

  • For B-cell recognition + activation

  • Allows for B-cell to perform antigen presentation

  • (Bind antigen to IgD on surface, internalize + digest, place on MCH II)

  • Higher on mature naive B-cells

(Slide #7). What are the types of Antigens?

1. Proteins/Peptides

2. Lipids (ex: Bacterial lipopolysaccharide membrane)

3. Sugars (ex: Polysaccarhride capsule of bacteria)

4. Nucleic Acid

What are Protein Antigens (B-cells)?

• B-cell presentation through antigen presenting cell/MCHII (2) to T-helper Cell

  • B-cells produce IgM/IgG or other antibodies

  • Memory B-cells formed

What are Non-Protein Antigens (Lipids/Sugars) for B-cells?

• Antigen binds directly to B-cell receptor → (IgD, maybe IgM) → leads to cross-linking of B-cell receptors

• Directly activates the B-cell (w/o any antigen presentation) + differentiates into → SHORT-LIVED PLASMA CELLS

• Plasma cells produce → IgM (ONLY)

• NO memory cells formed (SHORT-LIVED RESPONSE!)

What happens during FIRST INFECTION?

SLIDES 10-18

What happens with FOOD SENSITIVITY & FOOD ALLERGIES?

• Food sensitivity / intolerance:

  • IgG / IgA responses

  • Delayed response (hours to days)

  • 45% population

  • Ex: Gluten

• Food Allergies:

  • IgE responses Delayed response

  • Immediate response

  • 2% adults / 6-8% children

  • Ex: peanut, shellfish, eggs

(Slide #20). B-Cells: What kind of Switching and what kind of antibodies?

• Antibody class switching:

  • Occurs after B-cell activation (during division)

  • Induced by cytokines by T-helper cell

• Monoclonal antibodies:

  • Isolate B-cells and produce in cell culture system

B-cells: What is Gamma Globulin Therapy

• Treating a patient by injection of antibodies to a specific antigen

• Typically IgG

• Typically lasts 3-6 months

  • Ex: Respiratory Syncytial Virus (RSV), Measles, SARS-CoV2, Rh factor

B-Cells: Gamma Globulin Therapy→ What happens during pregnancy?

• Treating a pt by injection of antibodies to a specific antigen Typically IgG → (crosses the placenta)

  • Ex: Rh factor (D antigen on blood)

• If inject antibodies to Rh factor (Rhogam)

  • (Last trimester (3 months + after birth)

  • Antibodies will bind to baby’s blood entering mother which will be cleared by complement cscade before antigen presentation.

• IgG (long lived PC)

It’s going to take 2 wks to get that immune system for the infants

Possible problem of Rh- or Rh+ ?

• Look @ chart

What are blood types?

• Red Blood Cells:

  • Antigen A

  • Antigen B

  • Antigen A & B → (universal Recipient = NO antibodies

  • Neither Antigen A nor Antigen B → (Universal Donor = NO antigens)

• Plasma:

  • Anti-B antibody

  • Anti-A antibody

  • Neither anti-A nor anti-B antibodies

  • Anti-A & anti-B antibodies

(Slide #25). What are T-cells → T-cytotoxic cells (CD3+, CD8+ cells) → EFFECTOR CELLS?

1. Effector Cells → (target + eliminate current infection/ infected cells)

• Specific recognition of antigens on surface of infected cells (only recognize protein antigens)

  • (T-cell receptor)

  • Bind to antigen bound to MCH I molecule

  • Kills infected cell/foreign cell/cancerous cell

    • (Perforin + Granzymes)

Slide #25). What are T-cells → T-cytotoxic cells (CD3+, CD8+ cells) → MEMORY T-CELLS?

2. Memory T-cells

• Require re-stimulation to differentiate + divide → into (Effector cells + more memory cells)

• Half life of 5 years

(Slide #26). What are T-cells → T-cytotoxic cells (CD3+, CD8+ cells)

• Regulate immune reactions → control/activate adaptive immune response

• Get presented antigen by antigen presenting cells (conventional DENTRIC CELL, macrophage, B-cell, Basophil)

  • As a naïve Th0 (resting cell)

• Once presented antigen + exposed to CTYOKINES → differentiate / mature into:

  • Th1: Intracellular infections

  • Th2: Extracellular parasites (fungi, Protozoa, worms)

  • Tfh: (Follicular helper): Extracellular bacteria

  • Th17: Mucosal infections

  • Th22: Skin infections

Slide #27). What are T-cells → T-cytotoxic cells (CD3+, CD8+ cells) → Involved in what of the immune response?

• Involved in suppression of immune response (After infection cleared)

• Dysfunction related to autoimmune responses

(Slide #28). What is T-cell Cancer Therapy (CAR-T-cell — Chimeric Anitgen Receptor)?

1. Blood obtained from a Ca patient + T-cytotoxic cells purified

2. T-cytotoxic cells are engineered to have T-cell receptor that will bind to Ca antigen

3. T-cells are reintroduced back into pt where the T-cells specifically attack the Cancer