D’YOUVILLE COLLEGE
PMD 604 - ANATOMY, PHYSIOLOGY, PATHOLOGY II
Lecture 5: Immune system & blood groups
G & H chapters 34, 35 & Robbins chapter 5
1.
Body Defenses:
• nonspecific immunity – innate immunity: skin, mucous membranes (e.g.,
lungs, GI tract), and external secretions (e.g., saliva, tears) represent barriers to entry of
microbes
- phagocytes, natural killer cells (NK cells)
- acute inflammations, fever & antimicrobial chemicals obstruct spread of
infections
• specific immunity – acquired (adaptive) immunity: delivered by lymphocytes
- specific for offending agent; has capacity for recognition
- responds to specific macromolecular markers of foreign cells or organisms
(antigens), which present specific identifying features (epitopes) that elicit specific
responses
- specific immunity exhibits tolerance of ‘self’
- includes two patterns: antibody-mediated (AMI or humoral) response is
delivered by B-lymphocytes
- cell-mediated (CMI) response is delivered by T-lymphocytes
- AMI & CMI operate collaboratively with each other and with nonspecific
defenses (figs. 5 – 1, 5 – 2 & ppts. 1 & 2)
- specific immunity produces slow, weak initial response, but mounts
stronger response upon encounters that follow initial exposure (learning) (fig. 34 – 3
& ppt. 3)
2.
Lymphocytes:
• T-lymphocytes: progenitors of cell-mediated immunity and facilitators of
antibody-mediated immunity (humoral immunity)
- two well understood types: helper T-cells (TH) & cytotoxic T- cells (CTLs)
- originate in bone marrow; mature in thymus (primary lymphoid organ)
• B-lymphocytes: progenitors of antibody-mediated immunity assisted by
helper T-cells (TH)
- originate & mature in bone marrow (primary lymphoid organ)
• NK cells: ‘natural killer cells’ - large granulated lymphocytes that respond to
antibody-coated infective agents or to virus-infected or tumor cells (ppt. 4)
PMD 604, lec 5
3.
- p. 2 -
Lymphoid Tissues and Lymphocyte Traffic:
• primary lymphoid tissues:
- red bone marrow - repository of stem cells for formation of all types of
formed elements of the blood; site for development of immunocompetence & selfrecognition for B-lymphocytes
- thymus gland - site for development of immunocompetence & selfrecognition for T-lymphocytes
• secondary (peripheral) lymphoid tissues: spleen, regional lymph nodes, &
gastrointestinal lymphoid depots (tonsils, Peyer’s patches, & vermiform appendix) +
free lymphocytes scattered in various body tissues
• lymphocyte traffic
- lymphocytes produced in bone marrow develop further in marrow (Bcells) or migrate via bloodstream to thymus gland for further development (T-cells)
- competent cells from marrow and thymus circulate in bloodstream to
populate secondary lymphoid tissues (fig. 34 – 1 & ppt. 5)
- guarantees strategic location for encounters with antigens; antigenactivated lymphocytes linger in lymphoid depots and freely circulate in blood
4.
Maturation of Lymphocytes:
• lymphocyte clones: both T and B cells bear surface receptors (T cell
receptors or antibodies on B cells)
- receptors on one type of B or T cell are unique and all cells of a given type
constitute a clone; lymphocyte population of the body consists of a billion or more clones,
each with its own unique receptor
- clones are produced in maturation process & represent recognition
capability for virtually all possible antigens that may be encountered
• screening of lymphocyte clones: in the immature immune system,
lymphocyte screening (B-cells in bone marrow, T-cells in thymus gland), eliminates
(by apoptosis) clones that may attack self
- T cells or B cells that have undergone maturation and join the lymphocyte
traffic will be immunocompetent as well as self-tolerant
- until they have had their first encounter (sensitization) with the antigenic
determinant for which they bear specific receptors, they are considered naive
• antigens - complex molecules on the surface of microbes as well as normal
body cells; most antigens will have a number of immunogenic features, called
antigenic determinants (epitopes), so may stimulate several lymphocyte clones
• self-antigens are displayed on the surfaces of normal body cells and are
known as MHC (major histocompatibility complex) proteins; also known as HLA (human
leukocyte antigens) in humans
PMD 604, lec 5
- p. 3 -
- serve as presenters of antigens on surface of infected cells or on antigenpresenting cells (APC)
- class I MHC proteins are expressed by all cells and interact with cytotoxic
T cells (CTL) expressing CD8 receptor proteins; presentation of endogenous foreign
antigen may indicate virus infection or carcinogenic state (tumor cell)
- class II MHC proteins are expressed only by antigen presenting cells and
interact with helper T cells (TH) expressing CD4 receptor proteins; exogenous
foreign antigens are recognized this way
PMD 604, lec 5
5.
- p. 4 -
Antibody-Mediated Immunity (AMI):
• antibodies (fig. 34 – 4 & ppt. 6) – Y-shaped protein molecules that are
products of and receptors for B cells; circulate in plasma as immunoglobulins
- Fc fragment (constant fragment = stalk of Y) binds to surfaces of defensive
cells (e.g. B lymphocytes, phagocytes, mast cells, NK cells)
- has different properties for different classes of immunoglobulin
- FAB fragments (variable fragments = branches of Y) bind to unique
epitope of antigens
- antigen-antibody binding (immune complex formation) results in:
- neutralization of toxins, agglutination (clumping) of cell-bound
antigens, precipitation of soluble antigens, complement fixation --> promotes
phagocytosis (opsonization), inflammation (stimulation of mast cells, chemotaxis),
and lysis of offending cells (by activated complement and activated NK cells) (fig. 34
– 5 & ppts. 7 & 8)
• immunoglobulins (ppt. 9) –constitute fraction of plasma proteins and
include five categories – IgA (often a dimer – found in external secretions)
- IgD (poorly understood)
- IgM (pentamer - ppt. 10) delivers initial response (mainly to bacterial
infections), followed by IgG (commonest); both are complement-fixing antibodies
- IgE (involved in parasitic infections and in allergies), binds (via Fc
component) to mast cells to promote anti-allergen & anti-parasitic reactions
• sensitization (fig. 5 – 5 & ppt. 11):
- antigen-presenting cells (APC) are cells that have phagocytosed antigen
(macrophages, B cells, dendritic cells) (ppt. 12)
- antigens are presented on surface in association with MHC markers (ppt. 13)
- T cells of appropriate clone are activated by antigen recognition (clonal
selection) and stimulated to proliferate a population (clonal expansion) of active
helper cells as well as ‘memory’ cells (fig. 5 – 6 & ppt. 14)
- B cells activated by antigen binding proliferate a population of plasma
cells (secrete specific antibodies) as well as ‘memory’ cells; antibody titer (specific for
activating antigen) becomes elevated (fig. 5 – 7 & ppts. 15 & 16)
- clonal expansion (plasma & memory cell formation) can be undertaken by
B cells with or without the intervention of helper T cells, however, B cell activation is
facilitated by lymphokines from activated T helper cells
6.
Cell-Mediated Immunity:
• TH cells interact with antigen presenting cells and undergo clonal expansion
(fig. 5 – 6 & ppt. 14)
- these helper cells facilitate clonal expansion of several other cell types
specific for the antigen, i.e. same clone (cytotoxic T cells, NK cells), and activate
macrophages through release of lymphokines (interleukins) (fig. 34 – 8 & ppts. 17 &
18)
PMD 604, lec 5
7.
- p. 5 -
Blood Groups:
• red blood cell antigens: hundreds of antigens (not HLA) have been
identified on red cells; however, two main classes invoke immune responses of
clinical significance: A & B of the A-B-O system & D (Rh factor) of the Rh+/Rh- system
• ABO system (table 35 – 1):
- individuals with A antigen (agglutinogen A) are type A (genotype AO or
AA) & recognize B agglutinogen as foreign and make antibodies (anti-B agglutinins)
against it
- individuals with B antigen (agglutinogen B) are type B (genotype BO or BB)
& recognize A agglutinogen as foreign and make antibodies (anti-A agglutinins)
against it
- individuals with both antigens are type AB (genotype AB) & recognize
neither A agglutinogen nor B agglutinogen as foreign and make no antibodies against
them
- individuals with neither antigen are type O (genotype OO) & recognize A
agglutinogen & B agglutinogen as foreign and make antibodies (anti-A & anti-B
agglutinins) against them
- testing blood group can be achieved by obtaining blood sera containing
anti-A (from type B individual) or containing anti-B (from type A individual);
incompatibilities produce agglutination (clumping of red cells) (table 35 –2)
• Rh system
- individuals with D antigen (Rh factor) are type Rh+ (genotype Dd or DD)
& do not make antibodies
- individuals with no D antigen are type Rh- (genotype dd) & recognize Rh
factor as foreign and make antibodies (anti-D agglutinins) against it
• transfusion reaction: agglutination of incompatible donor cells
- agglutinated cells can block blood vessels (embolization) & eventually
undergo hemolysis releasing toxic substances that may cause circulatory shock &/or
kidney failure
8.
Active and Passive Immunization:
• vaccination: active immunization with sensitizing dose of antigen
- vaccines are prepared from dead microorganisms, weakened
microorganisms (attenuated), or inactivated exotoxins of microorganisms
- administration of vaccine elicits primary immune response so that
subsequent natural exposure to the antigen will vigorously and rapidly dispatch the
offending agent; an otherwise dangerous or lethal first encounter can be avoided
• antiserum administration: passive immunization with donor antibodies or
manufactured antibodies (monoclonal antibodies)
- temporary protection from infective organisms, e.g. inoculations for
travelers to exotic locations
PMD 604, lec 5
- p. 6 -
- protection during immune system’s development of sensitization to an
infection, e.g. rabies shots
- prevention of sensitization to Rh incompatibility between mother and
fetus (ppt. 19)