Immunology Part 1 Over view and the innate immune system

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Immunology-- Part 1 (Over view and the innate
immune system)

• Mhairi Sutherland

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Over view

• What are the main types of white blood cells?
• Name the two main types of immunity?
• What are the main distinctions between these two
  categories?
• What cells are involved in which aspects of the
  immune system?

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Lymphocytes

• Many types important in both humoral and
  cell-mediated immunity
• B-cells produce antibodies (APC cell)
• T- cells
• Cytotoxic T cells
• Helper T cells
• Memory cells

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Lymphocytes

• Natural Killer cells
• Large granular lymphocytes (not B or T)
• Kills tumor cells
• Kills cells infected with certain viruses
  (intracellular pathogens)

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Monocytes/Macrophage

• Phagocytosis and killing of microorganisms
• Activation of T cells and initiation of immune
  response
• Monocyte is a young macrophage in blood
• There are tissue-specific macrophages
• APC cells

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Dendritic Cells

• Phagocytosis and killing of microorganisms
• Function as antigen presenting cells (APC)
• In the blood and tissues mature and migrate to
  the lymph nodes

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Neutrophil

• Granulocyte
• Cytoplasmic granules
• Polymorphonuclear
• Phagocytosis
• Short life span (hours)
• Very important at clearing bacterial infections
• Innate Immunity

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Eosinophils

• Kills Ab-coated parasites through degranulation
• Involved in allergic inflammation
• A granulocyte
• Double Lobed nucleus
• Orange granules contain toxic compounds

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Basophils

• Might be blood Mast cells
• A cell-killing cells
• Blue granules contain toxic and inflammatory
  compounds
• Important in allergic reactions

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Antigen-presenting cells (APC)

• Highly specialized
• Process antigen and display peptide fragments on
  cell surface
• Involved in T-cell activation
• Macrophages, dendritic cells and B-cells

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Over view

• What are the main types of white blood cells?
• Name the two main types of immunity?
• What are the main distinctions between these two
  categories?
• What cells are involved in which aspects of the
  immune system?

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Immune system divisions

• Innate immunity
• First line of defense
• Adaptive (acquired) immunity
• Takes time to develop
• Humoral immunity (antibodymediated specific
  immunity)
• Cell-mediated immunity (The aspect of the
  adaptive immune response where antigen-specific T
  cell have a main role)

• Active immunity
• Passive or maternal immunity
• Injection of Immunoglobulin
• Absorption of maternal antibodies

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Innate vs. adaptive immunity

• Innate immunity
• First line of defense (present in all individuals
  at all times)
• Immediate (0 4 hours)
• Non-specific
• Does not generate lasting protective immunity
• Adaptive immune response (late gt 96 hours)
• Is initiated if innate immune response is not
  adequate (gt 4 days)
• Antigen-specific immunity
• Generates lasting protective immunity (e.g.
  Antibodies, memory T-cells)

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Over view

• What are the main types of white blood cells?
• Name the two main types of immunity?
• What are the main distinctions between these two
  categories?
• What white blood cells are involved in which
  aspects of the immune system?

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Immune system cells

• Innate immunity
• Granulocytes (i.e. neutrophils)
• Macrophages
• Dendritic cells
• Natural killer (NK) cells

• Adaptive immunity
• Lymphocyte
• B cells
• T cells
• Cytotoxic T cells (CTLs)
• Helper T cells (Th)
• Memory cells

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Innate immune system

• The first line of defense
• Penetration of the epithelial surface of the body
  by microorganism (e.g. bacteria)
• Engulfment of microorganism by macrophages,
  neutrophils, and dendritic cells
• Release of cytokines and chemokines
• Inflammation
• (Immunology animation Janeway)
• http//www.blink.biz/immunoanimations/

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Killing by granulocytes

• Macrophages and neutrophils recognize pathogen by
  means of cell-surface receptors
• Example mannose receptor, CD14 receptor,
  scavenger receptors, glucan receptor etc.
• Binding of MØ/neutrophils with pathogen leads to
  phagocytosis
• Bound pathogen is surrounded by phagocyte
  membrane
• Internalized (phagosome)
• Killing of pathogen (Phagolysosome)
• Oxidative burst (synthesis of hydrogen peroxide
  (H2O2)or free oxygen radicals)
• Acidification
• Antimicrobial peptides (e.g. defensins)
• Phagolysosome lysosome phagosome

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Phagocytosis
Mannose receptor
Lysosome
Phagosome
Scavenger receptor
LPS receptor (CD14)
Bacteria binding to macrophage receptors initiate
the release of cytokines and small lipid
mediators of inflammation
Phagolysosome
The macrophage expresses receptors for many
bacterial constituents
Macrophages engulf and digest bacteria to which
they bind
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Phagocytosis

• (Immunology animation Janeway)
• http//www.blink.biz/immunoanimations/
• Immune response (IV)
• 9.1 - Phagocytosis

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Humoral immune response
V region At binding

• Cell-surface immunoglobulin receptors (BCR)
  detect extracellular pathogens
• Once activated, secrete immunoglobulins as
  soluble antibodies
• Antibodies
• Variable region (2 identical antigen-binding
  sites)
• Constant region (determines how antibody disposes
  of the pathogen once it is bound)

Fc region
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Cell killing NK cells

• NK cells do not require prior immunization or
  activation
• They attach to target cells (ADCC)
• Cytotoxic granules are released onto surface of
  cell
• Effector proteins penetrate cell membrane and
  induce programmed cell death

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Inflammation
Inflammatory cells migrate into tissue, releasing
inflammatory mediators that cause pain
Bacteria trigger macrophages to release cytokines
and chemokines
Vasodilation and increased vascular premeability
cause redness, heat, and swelling
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Cytokines

• Low molecular weight, soluble proteins that are
  produced in response to an antigen and function
  as chemical messengers for regulating the innate
  and adaptive immune system
• Innate immune system
• Macrophages and Dendritic cells
• Tumor necrosis factor-alpha (TNF-?)
• Interleukin-1 (IL-1)
• Interleukin-12 (IL-12)
• Adaptive immune system
• T-lymphocytes
• Interleukin-2 (IL-2)
• Interleukin-4 (IL-4)