(1) adaptive immunity: a specific response such as production of antibody to a particular pathogen
depends upon lymphocytes which provide life-long immunity following exposure
key properties
: specificity, diversity, memory, multiplicity of mech, cellular division of labor, self regulation
(2) innate immunity: phagocytosis of microorganisms via macrophages without prior exposure; nonspecific
both are mediated by leukocytes (white blood cells)
all the cells that mediate innate immunity also participate in adaptive immunity
immunogenicity
: ability to elicit an immune response; must be antigenic
antigenicity
: ability to bind non-covalently to specific immunological receptor molecules (Ig or TCR); may be immunogenic
Components of the Immune System
cells of immune system originate and mature in bone marrow
Þ circulate in blood and lymph
monocytes in blood
Þ migrate into tissues and differentiate into macrophages
lymphocytes
Þ B cells (bone marrow derived or Bursa in birds)Þ plasma cells Þ secrete antibody
lymphocytes
Þ T cells (thymus derived), which activate other cells such as B cells or macrophages; or cytotoxic T cells, which kill cells infected with viruses
Only T and B cells bear highly diverse receptors, with each cell specific for a particular antigen
The antigen receptor of B lymphocytes is a membrane-bound form of the antibody they will secrete when activated (surface immunoglobulin)
Basic Principles of Innate and Adaptive Immunity
phagocytes (macrophages/neutrophils) of innate immunity provide first line defense to many microorganisms and control common bacterial infections
lymphoctyes of adaptive immunity provide a more versatile defense and increased protection from subsequent re-infection with the same pathogen
adaptive immune response is 4 to 7 days thus innate immunity helps control infections during this delay period
many bacteria activate phagocytes and trigger inflammatory responses (such as cytokine release) – these cytokines attract:
(1) leukocytes (neutrophils/macrophages) thru the skin to site of infection
(2) lymphocytes of adaptive immunity, which have meanwhile been activated by antigen draining from the site of infection via the afferent lymphatics
Lymphocytes (inactive B and T cells) are activated by antigen to give rise to clones of antigen specific cells that mediate adaptive immunity
Þ clonal selection theory
individual lymphocytes carry receptors of only one specificity, the specificity of each lymphocyte is different (each lymphocyte subject to allelic exclusion), and thus the millions of lymphocytes in the body give rise to millions of different specificities
only those lymphocytes that encounter an antigen to which their receptor binds will be activated to proliferate and produce many identical progeny (clones) which secrete antibody with a specificity identical to that of the surface receptor
this clonal selection of lymphocytes is the central principle of adaptive immunity
Instructional theory
(shown to be incorrect): molecule of antigen directly participates in shaping the structures of the corresponding antibody, and each lymphoid cell can therefore make antibodies of all specificities
The main distinctions between B and T lymphocyte receptors:
B cell receptor has 2 identical antigen recognition sites and can be secreted
T cell receptor has a single antigen recognition site and is always a cell-surface molecule
Lymphocytes proliferate in peripheral lymphoid tissue in response to trapped phag. cells carrying antigen
Once recognized, the lymphocytes (inactive B or T cells) stop migrating to the blood and enlarge
They then differentiate into activated B cells (effector cells able to secrete antibody) or T cells (effector cells that destroy infected cells or activate other cells of the immune system)
They then migrate thru the endothelial cells at sites of infection, signaled by cytokines released by inflammatory cells at these sites
Once antigen is removed, most of the antigen-specific cells generated undergo apoptosis
Immunological memory
: some persist after antigen removal and upon a 2nd encounter, ensures a more rapid and effective response
Basis of vaccines: primary immunization
Þ secondary or booster immunization Þ response occurs after shorter lag phase, achieves higher plateau level, and produces antibody of higher affinity
Interaction with other cells as well as antigen are necessary for lymphocyte activation
All lymphocte responses to antigen require a second signal from another cell
B-cell responses: signal is from a T cell
T-cell responses: signal is from antigen presenting cells (dendritic cells, macrophages, and B cells)
Dendritic cells: trap antigen, migrate to lymphoid tissues, present antigen to T cell
Recognition and Effector Mechanisms of Adaptive Immunity
B cells recognize antigen outside of cells (such as bacteria), while T cells detect antigens generated inside of cells (such as viruses)
effector mechanisms that operate to eliminate pathogens in adaptive immunity are identical to those of innate immunity
Defintions:
Active immunity
: immunity due to stimulation with antigen after an infection or other exposure
Passive transfer
: transfer of immune response from one indiv to another by means of serum
Passive immunity
: immunity via giving antibody from immune people
Adoptive transfer
: transfer of immune response from one indiv to another by means of cells
Immediate type hypersensitivity
: processes transferred by antibody tend to occur within sec/min/hrs
Delayed type hypersensitivity (DTH
): processes transferable by cells develop over days
Two Types of Adaptive Immunity:
(1) Humoral immunity
Fundamental strategy: antibody identify the structures that should be eliminated and then other molecular systems (complement) or cells (phagocytes) mediate the destruction
Exhibits specificty and memory
antibodies are found in plasma and extracellular fluids
The stem of the "Y" determines its isotype (5 major forms: G, A, M, E, D)
Each class engages a distinct set of effector mechanisms for disposing the antigen
Neutralization
:
antibodies bind to pathogen and block their access to cells they may infect or destroy
Important for protection against bacterial toxins and pathogens such as viruses
Opsinization
:
antibodies coat the pathogen and its constant region enables a phag. to detect, ingest, and destroy the bacterium
Complement system:
antibodies activate the complement system of plasma proteins which kill the bacterium directly or enable phag. to engulf and destroy bacteria they cannot recognize
Also enhances the bactericidal actions of phagocytes; hence it complements antibody
The complement system and phagocytes that antibody recruit are not antigen-specific, they depend upon antibody molecule to mark the particles as foreign
(2) Cell-mediated immunity
Some bacterial pathogens and parasites, and all viruses, replicate inside cells where they cannot be detected by antibodies; thus need T lymphocytes
Depends on direct interactions between T lymphocytes and cells bearing the antigen the T cell recognizes
Three types of T cells:
(1) Cytotoxic T cells – the most direct; recognize body cells infected with viruses
Antigens derived from the replicating virus are found on the surface of infected cells, cytotoxic T cells recognize these and kill the cell before viral replication is complete
(2) TH1 cells – more indirect; important in control of intracellular bacterial infections which enter macrophages and survive because the vesicles they occupy do not fuse with the lysosomes
activates macrophages, inducing the fusion of their lysosomes with the vesicles containing bacteria and also stimulates other antibacterial mechanisms of the phagocyte
releases cytokines that attract macrophages to the site of infection
(3) TH2 cells or helper T cells
Play a central part in the destruction of extracellular pathogens by activating B cells
T cells are specialized to recognize foreign antigens as peptide fragments bound to proteins of the major histocompatibility complex (MHC)
MHC class 1
display fragments of viral proteins on the cell surface and are recognized by cytotoxic T cells (CD8+)
MHC class 2
display peptides derived from pathogens living in macrophage vesicles or internalized by phagocytic cells or B cells and are recognized by TH1 or TH2 cells (CD4+)
critical distinction between humoral and cell mediated immunity
: effects of a humoral response are dependent for specificity on soluble molec, while the effects of a cell-mediated response are dependent for specificity on cell surface molecule synthesized by the cell on which they are expressed
both types of responses involve cells (lymphocytes) and soluble molecules (cytokines)
why have humoral and cell-mediated responses?
The immune response must be able to deal with both intracellular and extracellular stages in the life cycles of pathogens