Adaptive Immune System Flashcards

T Cells and B Cells

• T Cells

  • Mature in the Thymus.

  • Role: Cell-mediated response.

• B Cells

  • Mature in the bone marrow.

  • Role: Involved in Humoral Immunity: the production of antibodies.

• Both T and B cells are Lymphocytes.

  • Start development in the bone marrow.

Adaptive Immune Response

• 3rd Line of Defense: The Adaptive Immune Response (Lymphocytes - T & B cells).

T-Helper Cells (CD4+)

• Also known as T-helper cell.

• Interact with Professional APCs (Antigen-Presenting Cells).

  • Professional APCs cut up pathogens and present a piece to the adaptive immune system.

Antigen Presentation

• Non-professional APCs present an antigen about themselves.

  • This informs the immune cell the state of the cell.

• MHC (Major Histocompatibility Complex)

  • Acts like a holder that presents the antigen to the adaptive immune system.

MHC Class I

• Every cell has MHC Class I.

• Presents cytoplasmic antigen (e.g., viral) or mutation.

• Recognized by CD8+ T-cells.

  • Indicates the cell should be attacked.

CD8+ T-cells

• A T cell with a CD8 marker.

• Cytotoxic T cells recognize and attack cells presenting antigen via MHC Class I.

MHC Class II

• Only present in professional APCs.

• Read by CD4+ T-cells, which uses the information to help with the immune response.

• Does not signal for the APC to be attacked.

B-cells - Humoral Response

• humoral response - part of the adaptive immune system where B cells produce antibodies to neutralize pathogens and toxins in body fluids

• A molecule that can trigger an immune response.

• Primarily respond to extracellular antigens.

• B cell receptors recognize and attach to the antigen.

• The antigen is internalized into the B cell.

• Fragments of the antigen are presented on MHC class II proteins on the surface of the cell.

• A T helper cell (TH cell) that recognizes this antigen fragment is activated and releases cytokines, activating the B cell.

• The activated B cell undergoes clonal expansion, producing antibody-producing plasma cells and memory cells.

• Some cells proliferate into long-lived memory cells.

• Can be stimulated at a later date to become antibody-producing plasma cells.

• Some cells proliferate into plasma cells, which secrete antibodies into circulation.

  • Antibodies enter the bloodstream.

Antigen & Antibody Specificity

• Antigen has a constant region made up of two heavy chains (Fc)

• Antigen has a variable region made up light and heavy chain (Fab)

  • Fab recognizes the antigen

• Antigen - is any substance which triggers the production of antibody

• Polyclonal Antibody

  • Different clones of plasma cells release different antibodies that each recognize a unique epitope.

Antibody Functions

• Agglutination

  • Antibodies bind several antigens together.

• Opsonization

  • Antibody bound to the antigen triggers phagocytosis.

  • Antibody acts as a marker for a target.

• Activation of Complement System

  • Antibodies can activate the complement system.

• Antibody-Dependent Cytotoxicity

  • Antibody guides eosinophil to a parasite.

• Neutralization

  • Antibody can neutralize toxins.

Types of Antibodies

• Characterized by oligomeric state (number and arrangement of subunits or monomers).

• IgG

  • Abundance: 80%

  • Oligomeric State: Monomer (Y shape).

  • Role: Important in humoral immunity; placental protection.

• IgA

  • Abundance: 13%

  • Oligomeric State: Monomer or Dimer (Y shape).

  • Role: Secreted in saliva, initial barrier protection.

• IgM

  • Abundance: 6%

  • Oligomeric State: Pentamer (* shape).

  • Role: First to be secreted upon initial pathogen contact.

• IgD

  • Abundance: 0.02%

  • Oligomeric State: Monomer (Y shape).

  • Role: On the surface of B cells.

• IgE

  • Abundance: 0.002%

  • Oligomeric State: Monomer (Y shape).

  • Role: Attached to basophils and mast cells; helps with allergic reactions.

• Monoclonal Antibodies

  • Lab made antibodies

T cells-Cell-mediated Response

Cytotoxic T-cells (CD8+ T-cells)

• Respond to MHC Class I.

  1. Cell expresses MHC Class I and displays antigen.

  2. MHC Class I interacts with T-helper 1 (TH1), which releases cytokines.

  3. Cytotoxic T-cell gets activated and turned into memory cell.

• Activated cell will kill infected cell using perforin & granzyme.

• Memory T-cell will remember antigen (lasts for decades).

T- Helper Cells (CD4+ cells)

• TH1 helps initiate cell-mediated immunity.

  • Can secrete IFN\gamma-> activates macrophage.

  • Secretes IL-2 -> activates T-cell.

• TH2 secretes IL-4 -> activate mast cells, basophils, eosinophils -> allergy & parasite defense.

• TH17 secretes IL-17 -> activates neutrophils & unregulates inflammation.

Regulatory T- cells

• Terminates B & T cells that target healthy cells.

• Contains CD4+ & CD25+.

CAR (Chimeric Antigen Receptor) T-Cells: Engineering T-Cells for Cancer Immunotherapy

• A patient's leukocytes are collected by apheresis.

  • Ex-vivo cell processing: T-cell activation -> CAR transduction -> T-cell proliferation.

  • Use Virus retrovirus, lentivirus / Electroporation: RNA/DNA

  • Patient receives lymphocyte-depleting chemotherapy prior to T-cell infusion.

  • Patient receives CAR T-cell infusion.

  • CAR is specific to tumor antigen

  • Approved therapies target CD19 (tisagenlecleucel and axicabtagene ciloleucel) for acute lymphoblastic leukemia and large B-cell lymphoma.

Challenges with CAR T-cell Therapy

1. Target tumor antigen must be carefully selected (i.e. not too specific & not too ubiquitous).

2. Need to find a way to turn regulate CAR T-cells inside patients' body.

Other Immunotherapies

• Allogenic CAR-T-cell

  • An 'over the counter' method of receiving Car-T-cells

• Allergen

  • A molecule that can cause allergic reaction

  • Allergen -> APC MHCII -> TH2 -> turn on B cell -> IgE -> Histamine

  • Treg suppresses TH2 Cells

Allergy Immunotherapy

• An example is peanut immunotherapy