Second arm of the Immune System

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Second arm of the Immune System

• Cellular or Cell-mediated Immunity

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Second arm of the Immune System

• Cell mediated
• 1.) Involves T-cell lyphocytes

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Differentiation of T cells Pg. 468
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Description of T cells

• Blood Lymphocyte
• Antigen receptor on the cell surface
• T Cell Receptor (TCR)

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Description of T cells

• T Cell Receptor (TCR)
• Similar to the immunoglobin receptors
• 2 chains, not 4
• Bind antigen

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Description of T cells

• T Cell Receptor (TCR)
• Bind antigen
• Activate gene expression

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Description of T cells

• T Cell gene activity
• Produce interleukins
• Signaling molecule
• Induced to differentiate
• Interleukins stimulate the development of other T
  cells
• Different T cell functions

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Interleukins

• Interleukin-1
• Stimulates T-helper in presence of antigens
• Attracts Phagocytes in inflammation response
• Interleukin-2
• Involved in proliferation of antigen stimulated
  Tcells
• B cell differentiation and proliferation
• Activates T cytotoxic
• Interleukin 8
• Chemoattractant in inflammation
• Interleukin 12
• Differentiation of T-helper-like Tcells

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Second arm of the Immune System

• Cell mediated
• 2.) Direct attack against foreign cells (NON
  SELF)
• Organisms
• Tissues (transplants)
• Parasites

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Second arm of the Immune System

• Cell mediated
• 3.) Direct attack host cells displaying abnormal
  proteins. (SELF)
• Display of viral proteins
• Cancer cells

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Second arm of the Immune System

• Cell-mediated immunity
• Antigen whole cell

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Second arm of the Immune System

• Cell-mediated immunity
• Antigen whole cell
• fungi
• protozoans
• Mycobacterium tuberculosis
• enveloped viruses and infected cells
• cancer
• grafts

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Second arm of the Immune System

• Cell-mediated immunity
• specifically sensitized T lymphocytes

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Second arm of the Immune System

• Cell-mediated immunity
• specifically sensitized T lymphocytes
• attack and destroy antigen specifically
• Given instructions

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Sensitizing T lymphocytes

• T lymphocytes, already predestined to respond to
  particular antigens are in the lymph nodes,
  spleen, and blood.

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Sensitizing T lymphocytes

• Are activated by coming in contact with their
  specific antigen as presented by a macrophage.
• Clonal selection hypothesis.
• Only those T cells that fit the antigen will
  divide

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Sensitizing T lymphocytes

• Macrophage first ingests invader.
• Non-specific
• Digestion is incomplete
• Protein chunks are displayed on cell surface

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Sensitizing a T Cell

• Antigens are placed closely to Major Histo-
  compatibility Complex (MHC) molecules on cell
  surface of macrophage
• MHC define self
• MHC are unique in every individual

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Sensitizing a T Cell

• Macrophage presents antigen complex
• Antigen MHC

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Sensitizing a T cell

• T cell with the correct TCR
• Recognizes antigen
• Recognizes MHC

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Antigen Presentation

• Dependence on MHC

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Antigen Presentation
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Synthesis of sensitized T lymphocytes

• Activated T-cells develop into Specialized
  T-cells.

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Memory cells

• Remember the antigen and respond rapidly to a
  second exposure

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Types of T Cells

• Four Functional Types
• 1. Helper T
• 2. Cytotoxic T
• 3. Delayed Hypersensitivity T
• 4. Suppressor T

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T-Helper Sensitized T Lymphocyte

• TCR of T helper binds to the antigen/MHC of the
  presenting cell.
• Produce interleukins

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T-Helper Sensitized T Lymphocyte

• Produce interleukins
• Induce formation of T cytotoxic cells
• Activate macrophage
• Activate B cells and antibody production

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T helper cell pg. 476
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Total T helper function, Pg.481
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T-Cytotoxic sensitized T lymphocytes

• Interleukin 2 produced by T helper induces T
  cytotoxic to develop
• Cytotoxic TCR binds to the antigen/MHC of the
  presenting cell.
• T cytotoxic releases perforins which lyses the
  target cell.

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Action of cytotoxic T cells pg. 477
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Cytotoxic T cells

• Take about 2 weeks to develop

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T-Delayed Hypersensitivity Sensitized T
Lymphocytes

• Haptens
• Small, non-antigenic
• combine with other proteins, antigenic

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T-Delayed Hypersensitivity Sensitized T
Lymphocytes

• Poison Ivy
• Contact dermatitis
• Metals
• Cosmetics

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T-Delayed Hypersensitivity Sensitized T
Lymphocytes

• Role for cytokines
• Activate macrophage
• Inflammation results

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Poison ivy pg. 512
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T-Suppressor sensitized T lymphocytes

• A subset of T helper and T cytotoxic
• Supress Immune response
• B cells
• T cells

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Antigen Presentation macrophage to TCR
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AIDS

• Acquired immune deficiency syndrome

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AIDS

• Acquired immune deficiency syndrome
• HIV human immunodeficiency virus

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AIDS

• Acquired immune deficiency syndrome
• HIV human immunodeficiency virus
• infects and kills CD 4 (T helper cells)

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AIDS

• Acquired immune deficiency syndrome
• HIV human immunodeficiency virus
• infects and kills CD 4 (T helper cells)
• T helper cells
• assist B cells to produce antibodies

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AIDS

• Acquired immune deficiency syndrome
• HIV human immunodeficiency virus
• infects and kills CD 4 (T helper cells)
• T helper cells
• assist B cells to produce antibodies
• assist T cells to produce cytotoxic T cells

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Ratios
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Progression of AIDS

• T Cell Populations
• Normal 800-1000 T helper cells/mm2
• AIDS 200 T helper cells/mm2

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Progression of AIDS

• T cell populations are not static in advanced
  disease
• 1011 virus generated per day
• Last about 6 hours
• Cleared by host defenses

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Progression of AIDS

• T helper survive 2days (not years)
• 109 T helper are made/day to compensate
• 20 X 106 are lost per day

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Clinical AIDS

• Candida albicans (fungus)
• CMV eye infections (virus)
• TB (bacterial)
• Pneumocystis pneumonia (bacterial)
• Toxoplasmosis, brain (parasite)
• Kaposis sarcoma (virus, cancer)
• Hairy Leukoplakia (precancerous)

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Self Tolerance

• T cells develop in the thymus
• Clonal deletion
• Self-reactive lymphocytes are eliminated
• T cell Anergy
• T cells are silenced

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Autoimmune diseases

• Graves Disease
• Antibody binding / Receptor blocking
• Thyroid-stimulating hormone blocked
• Lupus
• Systemic autoimmune
• Antibodies against tissue/components
• Immune complex/Inflammation/deposition in kidney
• Insulin-dependent Diabetes
• Cell-mediated cytotoxicity

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Complement Activation