Lymphatic System
Lymphatic System
I. Non-specific responses -
General mechanisms for discouraging pathogens which do
not require the identity of the pathogen's antigenic nature.
These are the first line of defense against invasion by
pathogens.
A. Surface Membrane Barriers
1. Skin
a. acidic pH
b. Keratinization protects unbroken skin against
acids and bases of bacterial enzymes and toxins.
2. Mucous membranes
a. HCl in the stomach kills many pathogens,
denatures proteins
b. Saliva contains lysozyme, a bactericide
c. Lacrimal fluid contains lysozyme
d. Mucus traps organisms
B. Cellular And Chemical Defenses
1. Phagocytes - engulf particulates, including
microorganisms, which pass through the external barriers.
Examples: histiocytes in the lungs, Langerhans cells in the
skin, Kupffer cells in the liver, microglia in the nervous
system, macrophages in other tissues.
2. Natural killer cells - these large lymphocytes lyse
and kill tumor and virus-infected cells before activation of
a specific immune response.
3. Inflammation
a. reduces spread of damaging agents to nearby tissues
b. increases disposal of cell debris and pathogens
c. facilitates repair processes
d. caused by histamine and prostaglandins released
by basophils and other cells.
4. Anti-microbial proteins
a. Non-Specific complement activation
b. Interferons - block tumor and viral reproduction
c. Interleukin I - stimulates the immune response
5. Fever
a. Due to pyrogens secreted by leucocytes
b. Disrupts metabolism of pathogens
II. Specific Responses –
These second line of defense responses are activated by,
and directed against, a specific antigen.
Antigen - a protein or other substance which elicits immune
system activation in a "foreign" host.
A. Humoral Immunity - the B-cell response
1. Antigen challenge - "non-self" antigen binds to
antigen-specific surface receptors on generic B-cell.
2. Clonal selection - multiplication of B-cells
produces cells which all contain the same antigen-specific
surface receptor.
a. Primary response - plasma cells secrete free
antibodies of the same structure as the antigen-specific
surface receptor. The primary response takes 7 to 10 days
to reach maximum antibody levels.
b. Secondary response - memory cells which
retain the ability to quickly clone to produce more plasma
cells should the antigen be encountered again. The
secondary response takes from 1 to 2 days to reach
maximum antibody levels.
3. Antibodies form antigen-antibody complexes which
have the following affects:
a. Opsonization - labeling of antigens or foreign
cells
b. Neutralization - inactivation of bacterial toxins
c. Agglutination - clumping of cell-bound antigens
d. Precipitation - removes soluble antigen from
solution
e. Complement fixation - which causes cell lysis.
Complement protein binds to a site on the constant (Fc)
portion of the antibody.
4. Classes of antibodies:
IgD - (monomer) antigen receptor on B-cell
IgM - (pentamer) first antibody released by plasma
cells during primary response
IgG - (monomer) comprises most circulating
antibodies, both 1o and 2o responses
IgA - (dimer) antibody found in secretions
IgE - (monomer) secreted in mucosae, mediates
inflammation in allergic reaction.
B. Cell Mediated Immunity - the T-cell response -
requires an intermediary cell to be stimulated. These
intermediary cells can be infected body cells or
macrophages as below. Identification of these cells and
their antigens is by means of MHC proteins. MHC (Major
Histocompatibility Complex) antigens are recognition
proteins which identify a cell as being "self". They are
displayed together with part of the antigen from invading
viruses to be recognized by T-cell lymphocytes. There are
two classes of MHC antigens: Class I is present on all body
cells; Class II is present only on cells of the immune
system.
There are several types of T cells.
1. generic cytotoxic T-cells
a. respond to antigens complexed by MHC I
proteins from infected body cells.
b. attack and kill virus or bacteria-infected cells and
tumor cells
c. maintain immunologic surveillance
d. clone to produce mature cytotoxic cells and
cytotoxic memory cells
2. Helper T-cells
a. respond to antigens complexed with MHC II
proteins on antigen presenting cells
b. act as costimulator cells for B-cells and other T-
cells and . Activated Helper cells release interleukin II and
act as a costimulator for an effective B-cell response.
c. release interleukin I which acts as a costimulator
for T-cell production.
3. Suppressor T-cells - regulatory cells which tend to
shut down B and T-cell responses.
4. Cytokines - chemical mediators involved in cellular
immunity.
a. interleukin I - costimulator for activated T-cells
b. interleukin II - stimulates both B and T-cell
proliferation
c. MAF - macrophage activating factor
d. MIF - macrophage migration inhibiting factor
e. perforin - causes cell lysis
f. lymphotoxin - kills cells by fragmenting their
DNA
g. tumor necrosis factor - specialized destruction
of tumors.
C. Immunocompetence: (often called immune
tolerance because it is the tolerance of your own cells) is
the ability of your immune system to recognize self vs.
non-self (anti-self, foreign) antigens. This ability is
conferred during childhood. For T cells the site for this is
the thymus gland which ceases this activity after puberty.
The site for the B cells is unknown. The name B cell comes
from the Bursa of Fabricus, a gut-associated site which is
the site of immunocompetence in chickens. Humans don't
have a Bursa, so a "Bursa Equivalent" confers
immunocompetence, possibly the marrow, but recent
evidence suggests an area analogous to the bursa in the
distal GI tract. During childhood, immature or pre-
lymphocytes originate in the marrow, travel to the thymus
(or other area) for immuno-competence, then travel to the
lymph nodes where they proliferate in response to antigenic
stimulation.
D. Hypersensitivity
1. Type I Hypersensitivity - this is the basis for
allergic reactions. Usually this occurs when you have been
exposed to non-pathogenic foreign antigen and built up
memory cells. Subsequent exposure causes these cells to
become plasma cells which release large amounts of IgE
antibodies. IgE antibodies bind to basophils and mast cells
causing them to release granules containing histamine and
other inflammatory chemicals. This is the basis for the
vascular changes seen in allergy and anaphylaxis.
2. Type II Hypersensitivity - this is a type of
autoimmunity. Autoimmune disorders can result when
host antigens are similar to invading antigens and cross
reactions occur, or from mutations of antigens, or by
antigens which are masked or not present during the period
of immunocompetence, or which are altered by
environmental or disease factors and cease to be recognized
as "self", or by lack of immune tolerance (another term for
immunocompetence). Among diseases which have been
classified as autoimmune are: multiple sclerosis,
myasthenia gravis, Graves disease, andsome forms of Type
1 diabetes mellitus.
3. Type III Hypersensitivity occurs when the
antigen-antibody complexes produced by normal immune
system reactions are not removed and lodge in the
basement membrane of endothelial cells and in other
connective tissues. Their presence induces massive
inflammation by triggering the complement pathway with
resulting cell lysis, hemorrhage, and tissue destruction.
Examples include: systemic lupus erythematosus (SLE),
rheumatoid arthritis and acute glomerulonephritis.