Description

This video covers the humoral immune system and its role in immune responses.

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All information in my immunology videos is sourced from:

• Book: Immunology, Eighth Edition by David Male, Jonathan Brostoff, David Roth, and Ivan Roitt
• Additional research: PubMed
• University lecture materials

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Types of Immune Responses:

• Humoral Immune Response
• Cellular Immune Response
• Immunological Memory/T-cell Tolerance
• Hypersensitivity

Steps in Humoral Immunity:

1. Antigen Entry: Extracellular antigens enter the body.
2. Phagocytosis and Inflammation: Professional phagocytes attack the antigen.
3. Antigen Presentation: Peptides presented on MHC II to Th0 cells.
4. B-cell Differentiation: Specific antibodies are produced.

Phagocytosis and Inflammation:

Professional Phagocytes:

• Neutrophils
• Macrophages/Monocytes
• Mast Cells
• Dendritic Cells

Steps in Phagocytosis:

1. Binding:
   • Mannose Receptor: Binds mannose on microbial surfaces.
   • Toll-Like Receptor (TLR): Recognizes microbial patterns.
   • CD14: Binds lipopolysaccharide (LPS) of Gram-negative bacteria.
   • C3b – C3b Receptor: Indirect opsonization (enhances binding).
   • Fc-Receptor: Binds to the Fc portion of antibodies (direct opsonization).
2. Engulfment: Formation of pseudopods to enclose the antigen.
3. Phagosome Formation: Oxygen-dependent digestion via Reactive Oxygen Species (ROS).
4. Lysosome Fusion: Breakdown of microbes via:
   • Enzymes (Proteolytic, Hydrolytic)
   • Antimicrobial Peptides (Defensins)
   • Acidic Reactions (Low pH)
   • Lactoferrin (Neutrophils)
5. Antigen Presentation: Fragments of the microbe are displayed on MHC II.

Pro-Inflammatory Cytokine Release:

• IL-8: Chemotaxis for leukocytes.
• IL-1: Activates T-lymphocytes and macrophages.
• IL-6: Activates T- and B-lymphocytes.
• TNF-α: Activates endothelium, promoting neutrophil extravasation.
• IL-12: Activates natural killer (NK) cells.

Systemic Response of IL-1, IL-6, and TNF-α:

• They act as endogenous pyrogens (cause fever).
• Travel to the hypothalamus → Release Prostaglandin E2 (PGE2) → Increases body temperature.
• IL-6 travels to the liver → Stimulates release of acute-phase proteins (CRP and MBL).

Incomplete Phagocytosis:

• Some microbes evade destruction inside the phagocyte:
  • Listeria: Releases Listeriolysin.
  • Mycobacterium: Releases Catalase.

Activation of Naïve T Helper Cells:

• Three activation signals are needed:
  1. 1st Signal: TCR (with CD4/CD3) binds to MHC II.
  2. 2nd Signal: B7 binds to CD28.
  3. 3rd Signal: IL-4 (from mast cells/Th1).
• Naïve Th0 releases IL-2 (autocrine) to promote its growth.
• Th0 undergoes clonal expansion and differentiates into effector Th2 cells.

Effector Th2 Functions:

• Expresses CD40L to assist B-cell activation.
• Releases cytokines:
  • IL-10: Suppresses Th1 function.
  • IL-4, IL-5, IL-6: Stimulate B-cell differentiation.

B-Cell Activation in Secondary Lymphoid Organs:

• B-cells have B-cell Receptors (BCR): IgD/IgM with Iga and Igb signaling components.
• B-cells migrate to the secondary follicle to interact with T-cells.

Three Activation Signals for Naïve B-Cell Differentiation (T-cell Dependent):

1. 1st Signal: BCR binds to antigen.
2. 2nd Signal: B-cell binds to active Th2 via:
   • MHC II – TCR
   • CD40 – CD40L
3. 3rd Signal: IL-4, IL-5, IL-6, IL-10, IL-2, IFN-γ (determines antibody class).

• B-cells then differentiate into:
  • Memory B-cells (long-term immunity).
  • Plasma Cells (produce antibodies).

T-Independent B-Cell Differentiation:

• Occurs when BCR binds to polysaccharides or carbohydrate antigens.
• Strong activation signal → Differentiation into IgM-secreting Plasma Cells.
• Does not produce memory B-cells.

Primary vs. Secondary Humoral Immune Response:

• Primary Response:
  • First exposure: IgM is produced first, followed by IgG.
  • IgG levels are higher than IgM.
• Secondary Response:
  • Second exposure: IgM response is the same.
  • IgG response is stronger and faster due to memory B-cells.

Transcript

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