Elements of Innate and Acquired Immunity

Innate or Natural Immunity

1.     Physiological barriers

  • Skin
  • Epidermis, Acid pH of sweat, lysozyme
  • Mucous membranes
  • Mucus, hydrolytic and proteolytic enzymes, Low pH in vagina and Stomach

2.     Phagocytosis

  1. General Properties

a.     Stages

1.     ingestion

2.     formation of phagocytic vacuole (phagosome)

3.     fusion of phagosome with lysosome

4.     destruction of bacterium of virus

b.     Opsonization- increases rate of phagocytosis

1.     due to antibodies or complement components

c.      Oxidative mechanisms of killing

1.     Oxidative burst

2.     Formation of reactive oxygen intermediates

3.     Examples of enzymes

a.     NADPH oxidase, myeloperoxidase, nitric oxide synthetase

d.     Non-oxidative mechanisms of killing

1.     degradative enzymes- proteases, lysozyme, acid phosphatases

2.     Low pH

3.     Lactoferrin

e.     Bacterial avoidance

  • Capsules, thick waxy cells, catalase production, inhibition of phagosome-lysosome fusion

2. Polymorphonuclear leukocytes

a.     Predoninant leukocyte in blood

b.     short-lived

c.      Acute phase reactants- present at injured or infected site with min to hrs

d.     Neutropenia- PMN deficiency-characterized by recurrent, chronic bacterial infections

3.Monocytes/macrophages

a.     long-lived

b.     common cellular component of chronic inflammation

c.      important in phagocytosis, Ag presentation, cytokine production, and synthesis of complement components

4.Null lymphocytes (NK cells)

3. Inflammation

  • initiated by tissue damage from exogenous or endogenous sources
  • can be mechanical, physical, chemical, biological, or immunological
  • Hallmark signs of inflammation
  1. Swelling (tumor)- leakage, accumulation of fluid (edema)
  2. Redness (rubor)- dilitation of BV
  3. Heat (calor)- dilitation of BV
  4. Pain (dolor)- injury, compression of nerve endings
  5. Loss of function- swelling, compression of nerves

4. Fever

  • induced by bacterial products such as endotoxin
  • mediated by endogenous substances such as IL and Interferons

5. Other biological active substances

  • Interferons- inhibit viral replication
  • Smallmolecular weight compounds
  • Histamine- released from granules of mast cells, basophils
  • Arachadonic acid metabolites- prostaglandins and leukotrienes

Acquired or Adaptive immunity

  • requires B and T cells with their accessory cells
  • B and T cells express their functional activity only AFTER they are activated by exposure to that antigen.

Primary Lymphoid Organs

1.     Thymus- T cells only; only 5-10% of the thymocytes make it as T cells; thymus decreases in size as you age

2.     Bone Marrow- B cells; Stem cells give rise to variety

  • B cell maturation involves the expression of surface Iglobulin

3.     Fetal liver- B cells during development

Secondary Lymphoid organs

  • sites of lymphocyte activation and expression of B and T cell activities

1.     Gen. Features

  1. Lymphoid follicle
  2. Germinal center- region of a lymphoid follicle where B cells are differentiating into plasma cells

2.     Spleen

  1. largest secondary lymphoid organ
  2. ****filters blood, important in control of blood-borne bacteria
  3. White pulp- site of lymphocyte activation, proliferation , and differentiation
  4. Red pulp- bloo-filled sinuses with many macrophages involved in phagocytosis of bacteria

3.     Lymph Nodes

  1. filter lymph
  2. Contain germinal centers (B cells), paracortical regions (T cells), and medullary sinuses (macrophages and plasma cells)

MALT

  • tonsil’s peyer’s patches, appendix, diffuse lymphoid tissue in mucosa
  • Primary sites of immune response in Gi and respiratory areas.
  • IgA is predominant at these sites

Diffuse lymphoid tissue- every externally-exposed surface (ex. skin, asophagus, and vagina)

Circulation of Lymphocytes

  • lymphocytes are not static, they circulate

High Endothelial venules (HEVs)

  • primary sites of entry of lymphocytes from the bloodstream
  • found in cortex of lymph nodes and other lymphoid organs
  • lined by activated endothelial cells that express adhesion proteins such as adhesion molecule-1 (ICAM-1)

Fate of Antigen

1.     Ag transport to lymphoid site

  1. either as a free Ag or w/ a migrating monocyte or macrophage

2.     Lymphocyte activation

3.     Second Signal

  1. nearly all immune responses require Ag binding + a second signal.  This signal consists of interleukins (ILs) produced by helper T cells and macrophages

4.     Lymphocyte proliferation

  1. results in increased number of B and T cells responsive to that antigen
  2. leads to amplification
  3. and also leads to memory

5.     Expression of Ab or T cell function

  1. occurs after the preceding steps; can take several days
  2. results in the delay in exposure and expression of protective T cell activities (such as delayed type hypersensitivity or cytotoxic T cell activity)

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