1. The Specific Immune Response
Specific Defense:
The Specific Immune Response

2. Third Line of Defense Is called specific immunity
The body’s ability to recognize and defend itself against distinct invaders and their products
Is a “smart” system whose “memory’ allows it to respond rapidly to a second encounter with a pathogen

3. Elements of Specific Immunity
Is acquired over time
Antigens trigger specific immune responses
Various cells, tissues, and organs are part of specific immunity
Includes B and T lymphocytes

4. Antigens Molecules that trigger a specific immune response
Include components of bacterial cell walls, capsules, pili, and flagella, as well as proteins of viruses, fungi, and protozoa
Food and dust can also contain antigenic particles
Enter the body by various methods
Through breaks in the skin and mucous membranes
Direct injection, as with a bite or needle
Through organ transplants and skin grafts

5. Types of Antigens

6. Properties of antigens
Antigens are recognized by the 3-dimensional shapes of their antigenic determinants (epitopes).
Large molecular masses (5, ,000).
Chemical nature
Complexity
Incomplete antigens (haptens)

8. Lymphatic System Screens the tissues of the body for foreign antigens
Composed of lymphatic vessels and lymphatic cells

9. Lymphatic Vessels
Form a one-way system that conducts lymph from local tissues and returns it to the circulatory system
Lymph is a liquid with similar composition to blood plasma that arises from fluid leaked from blood vessels into surrounding tissues

11. Lymphoid Cells Develop from stem cells in the red bone marrow
Includes lymphocytes, the smallest of the leukocytes

19. Lymph Nodes
Houses leukocytes that recognize and attack foreign antigens present in the lymph
Concentrated in the cervical (neck), inguinal (groin), axillary (armpit), and abdominal regions
Receives lymph from afferent lymphatic vessels and drains lymph into efferent lymphatic vessels

21. Other Lymphoid Tissues and Organs
Spleen
Similar in structure and function to the lymph nodes
Filters bacteria, viruses, toxins, and other foreign matter from the blood
Tonsils and mucosa-associated lymphoid tissue (MALT)
Physically trap foreign particles and microbes
MALT includes the appendix, lymphoid tissue of the respiratory tract, and Peyer’s patches in the wall of the small intestine

22. B Lymphocytes Arise and mature in the red bone marrow
Found primarily in the spleen, lymph nodes, red bone marrow, and Peyer’s patches
Small percentage of B cells circulate in the blood
Major function is the secretion of antibodies

24. Antibodies
Also called immunoglobulins (Ig) & make up 20% of plasma proteins.
Soluble, proteinaceous molecules that react specifically with the antigen that stimulated their production.
Secreted by plasma cells, which are B cells actively fighting exogenous antigen
Considered part of the humoral immune response since bodily fluids such as lymph and blood were once called humors
Antibody mediated immunity is important mainly
in toxin-induced disorders
against capsulated bacteria
in the prevention of some viral infections.

31. Antibody Function
Antigen-binding sites are complementary to antigenic determinants (epitopes), they are hypervariable regions within the variable domains of heavy and light chains
Due to the close match can form strong, noncovalent interactions
Hydrogen bonds and other attractions (van der Waals, electrostatic) may also be involved

32. Antibody Function Function in several ways Activation of complement
Stimulation of inflammation
Agglutination
Neutralization
Opsonization

34. Classes of Antibodies
A single type of antibody is not sufficient for the multiple types of invaders to the body
The class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed
5 different classes of antibodies

35. Immunoglobulin classes
Depends upon the class of the heavy chain
γ chain in IgG
µ chain in IgM
 chain in IgA
ε chain in IgE
δ chain in IgD

36. Immunoglobulin classes
IgG is divalent. It crosses the placenta. 80% in serum. 2ry immune response.
It is agglutinating, fixes complement, neutralizing.
IgM is a pentamer. 6% in serum. 1ry immune response.
IgA is dimer in secretions (milk, saliva, tears, respiratory & intestinal secretions) , monomer in serum (13%)
IgE bound to the surface of basophils and mast cells, <1%
Increases in anaphylactic reactions and helminth infections.
IgD bound to the surface of some cells, <1%.

38. Characteristics of the Five Classes of IGs

39. Characteristics of the Five Classes of Immunoglobulins
Structure
( Molecular Weight
In Daltons)
Name function(s) Location(s) percentage in serum
IgG Complement activation, agglutination Monomer (180,000) serum, intercellular fluid
opsonization, and neutralization;
crosses placenta to protect fetus
IgM Complement activation, agglutination, Pentamer (900,000) serum
and neutralization
IgA Agglutination and neutralization Monomer (150,000) External secretions,
Dimer (300,000) including milk
IgE Triggers release of histamines Monomer (200,000) Serum, <1
from basophil mast cells mast cell surfaces
IgD Unknown Monomer (180,000) B cell surface (as receptors) <1

41. B Cell Receptor (BCR)
Is an antibody that remains associated with the cytoplasmic membrane
Each B lymphocyte has multiple copies of a single type of BCR (105)
Antigen binding site is identical to that of the secreted antibody for that particular cell
The randomly generated antibody variable region determines the BCR (it is not formed in response to antigens)

43. B Cell Receptor (BCR)
Each BCR is complementary to only one antigenic determinant
The BCRs on all of an individual’s B cells are capable of recognizing millions ( ) of different antigenic determinants

44. T Lymphocytes Produced in the red bone marrow and mature in the thymus
Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches
Part of the cell-mediated immune response because they act directly against various antigens
Endogenous invaders
Many of the body’s cells that harbor intracellular pathogens
Abnormal body cells such as cancer cells that produce abnormal cell surface proteins

45. T Lymphocytes
3 types
Cytotoxic T cells
2 types of helper T cells

47. Cytotoxic T cells (TC Cells)
Distinguished by the CD8 cell-surface glycoprotein
Directly kill certain cells
Cells infected with viruses and other intracellular pathogens
Abnormal cells, such as cancer cells

48. Helper T Cells (TH Cells)
Distinguished by the CD4 cell-surface glycoprotein
Function to “help” regulate the activities of B cells and cytotoxic T cells during an immune response
Secrete various soluble protein messengers, called cytokines, that determine which immune response will be activated

49. Helper T Cells (TH Cells)
2 types
Type 1 helper T cell (TH1)
Assist cytotoxic T cells
Express CD26 and a cytokine receptor named CCR5
Type 2 helper T cell (TH2)
Assist B cells
Have cytokine receptors CCR3 and CCR4

50. Cytokines
Soluble regulatory proteins that act as intercellular signals when released from certain body cells
Immune system cytokines signal among various leukocytes
The complex web of signals among all the cell types of the immune system is referred to as the cytokine network

51. Cytokines of the Immune System
Interleukins (ILs)- signal among leukocytes
(IL-1 produced by macrophages and activates various cells eg T & B cells)
(IL-2 produced by T helpers and stimulate growth of T cells)
Interferons (IFNs)- antiviral proteins that may act as cytokines (especially gamma)
Growth factors- proteins that stimulate stem cells to divide, maintaining an adequate supply of leukocytes
Tumor necrosis factors (TNFs)- Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammation (cachectin)
Chemokines- signal leukocytes to go to a site of inflammation or infection and stimulate other leukocytes

52. Lymphocyte Editing by Clonal Deletion
Vital that immune responses not be directed against autoantigens
Body “edits” lymphocytes to eliminate any self-reactive cells

54. Major Histocompatibility Complex (MHC)
Group of antigens first identified in graft patients
Important in determining the compatibility of tissues in successful grafting
Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals
Function to hold and position antigenic determinants for presentation to T cells

55. Major Histocompatibility Complex (MHC)
Antigens bind in the antigen-binding groove of MHC molecules
2 classes of MHC proteins
MHC class I (A, B, C)
MHC class II (Dp, Dq, Dr)

58. Antigen Processing T-independent antigen
Large antigen molecules with readily accessible, repeating antigenic determinants
B cells can bind these directly without being processed
Stimulates B cells to differentiate into a plasma cell and produce antibodies

60. Antigen Processing T-dependent antigens
Smaller antigens with less accessible antigenic determinants
B cells require involvement from helper T cells to target these antigens
Helper T cells are assisted by leukocytes that process the antigen to make the antigenic determinants more accessible
Processing is different based on whether the antigen is exogenous or endogenous

61. Processing of Exogenous Antigens
APC internalizes the invading pathogen and enzymatically digests it into smaller antigenic fragments which are contained within a phagolysosome
Phagolysosome fuses with a vesicle containing MHC II molecules
Each fragment binds to the antigen-binding groove of a complementary MHC II molecule
The fused vesicle then inserts the MHCII-antigen complex into the cytoplasmic membrane so the antigen is presented on the outside of the cell

64. Processing of Endogenous Antigens
The intracellular pathogens are also digested into smaller antigenic determinants
Each fragment binds to a MHC I molecule located in the endoplasmic reticulum membrane
The membrane is packaged into a vesicle by a Golgi body which is inserted into the cytoplasmic membrane so the antigen is displayed on the cell’s surface

65. Humoral Immune Response
Body mounts humoral immune responses against exogenous pathogens
Components of a humoral immune response
B cell activation and clonal selection
Memory B cells and the establishment of immunological memory

66. Plasma Cells
Make up the majority of cells produced during B cell proliferation
Each plasma cell secretes only antibody molecules complementary to the specific antigenic determinant
Are short-lived cells that die within a few days of activation, though their antibodies and progeny can persist

68. Memory B Cells
Cells produced by B cell proliferation that do not secrete antibodies
Cells that have BCRs complementary to the specific antigenic determinant that triggered their production
Long-lived cells that divide only a few times and then persist in the lymphoid tissue
Are available to initiate antibody production if the same antigen is encountered again

70. Cell-Mediated Immune Response
Responds to intracellular pathogens and abnormal body cells
The most common intracellular pathogens are viruses but the response is also effective against intracellular bacteria
Triggered when antigenic determinants of the pathogen are displayed on the host cell’s surface

72. The perforin-granzyme cytotoxic pathway
Tc cells have vesicles containing cytotoxins (perforins & granzymes)
Upon attachment of Tc cell to a target, the vesicles release the cytotoxins
Perforins aggregate into a tubular structure in the infected cell membrane forming a channel
Granzymes move through this channel into target cells and activate apoptotic enzymes
Tc disengages and moves on to another infected cell.

73. The CD95 cytotoxic pathway
CD95 is present on cell membrane of most body cells
Its receptor CD95L is present on activated Tc
CD95L from activated Tc binds to CD95 on target cell, this activates enzymes that trigger apoptosis

75. T Cell Regulation
Careful regulation of cell-mediated immune response to prevent T cells from responding to autoantigens
T cells require additional signals from an antigen presenting cell
Interaction of the T cell and antigen presenting cell at an immunological synapse stimulates the T cell to respond to the antigen

76. Acquired Immunity
Specific immunity acquired during an individuals life
2 types
Naturally acquired- immune response against antigens encountered in daily life
Artificially acquired- response to antigens introduced via a vaccine
Further distinguished as either active or passive
Active- active response to antigens via humoral or cell-mediated responses
Passive- passively receive antibodies from another individual

77. A Comparison of the Types of Acquired Immunity