Final: Ch 13: Host Defenses II Flashcards
Lines of Defense
If the first and second lines fail, then the third line is activated
B and T lymphocytes undergo a selective process that prepares them fro reacting only to one specific antigen or immunogen
Nonspecific resistance: first and second line of defense
First line: intact skin, mucous membranes and their secretions, normal microbiota
Second line: phagocytic white blood cells, inflammation and fever, antimicrobial substances
fevers and inflammation are non specific - they’ll kill the bacteria but will also harm your normal biota
Specific resistance (responses of immune system): third line of defense
specialized lymphocytes: B and T cells
antibodies
specific response is controlled by B cells and T cells
2 features the characterize the specific immune response
specificity
memory
to have specific immunity: every cell has to have specific receptors or protein on the outside of them
specificity
antibodies produced against the chickenpox virus will not function against the measles virus
memory
lymphocytes have been programmed to recall their first engagement with an antigen and rush to attack once again
Immune serum globulin/gamma globulin
antibody rich part of serum
Antigens/immunogens
molecules that stimulate a response by B and T cells
protein or polysaccharide molecules on or inside cells and viruses
any exposed or released protein or polysaccharide is potentially an antigen
antigens are highly individual and stimulate specific immunity
antibodies will bind to the antigen
Antigens - located on outside of the pathogen. the pathogen needs these things and we need them to be able to identify the pathogen
Lymphocytes and the immune response
all lymphocytes arise from the same basic stem cell type
B-cells mature in specialized bone marrow sites
T-cells mature in thymus
Both cell types migrate to separate areas of lymphoid organs
B and T cells constantly recirculate thru the circulatory system and lymphatics, migrating into and out of the lymphoid organs
Markers and receptors
all cells have a variety of different markers on their surfaces for detection, recognition and communication
Major histocompatibility complex (MHC)
these “self” receptors are expressed on the outside of an individuals cells are specific to that individual
when you hear of the importance of tissue typing = referring to the type of MHC receptor
important in transplants
Identify that a cell is self and binds antigens for antigen presentation
Lymphocyte receptors
major role is to “accept” or “grasp” antigens in some form
B-cells: have receptors that bind antigens
T-cells: have receptors that bind antigens that have been processed and complexed w/MHC molecules on the presenting cell surface
receptors have the capacity to respond to a nearly infinite number of unique antigens
B cell
mature in bone marrow
can bind directly onto the antigen
T cell
mature in thymus
will eventually bind onto the antigen but have to have it presented to them (antigens have to have been processed and complexed w/MHC molecules on the presenting cell surface)
Cluster differentiation (CD)
different B and T cells will have different types of receptors (CD receptors)
specific types of cells will have specific CD receptors
Stage 1: the Development of Lymphocyte Diversity
T-cell
specific events in T-cell maturation
-maturation of T cells and development of their recpetors is directed by the thymus and its hormones
Different CD receptors are present on the T cell & bind to MHCs and other molecules
-these CD receptors are used clinically to ID the various cells of the immune system
Stage 1: the Development of Lymphocyte Diversity
B-Cell
Stromal cells in the bone marrow provide chemical signals that initiate B-cell development
circulate in the blood,
“homing” to specific sites in the lymph nodes, spleen, and gut associated lymphoid tissue
carry and secrete antibodies
free floating in the blood or on the surface of the B cell?
B cells need to get these antibodies onto their membranes
Immunoglobulin molecule (the specific B-cell receptor)
Immunoglobulin (IgG) - large glycoprotein molecules that serve as the antigen receptors of B cells
-when secreted: are antibodies
IgG structure
Epitope - portion of antigen that binds antibody
Antigen binding sites - pockets in the ends of the forks of the molecules that can be highly variable in shape to fit a wide range of antigens
Variable regions - areas of extreme versatility in aa sequence from one clone to another
Constant regions - amino content does not vary greatly from one antibody to another; all humans have the same constant region
Antibodies have 2 parts to them: the light chain and the heavy chain
The origin of immunologic diversity
By the time B and T cells reach lymphoid tissues, each one is equipped to respond to a single unique antigen
Diversity
generated by rearrangement of gene segments that code for antigen receptors on T and B cells
- every possible recombination occurs, leading to huge assortment of lymphocytes
- estimated 10 trillion different specificities
involves clonal selection and expansion
Clone
each genetically unique line of lymphocytes arising from recombination
Clonal deletion
removes any T or B cell that can potentially react to self before any potential damage can occur
deleting all the clones that are going to potentially attack host cells
Clonal selection
the mechanism by which the correct B or T cell is activated by any incoming antigen
each genetically distinct lymphocyte expresses specificity to a distinct antigen
Clonal expansion
the rapid multiplication of B of T cell clones after activation by an antigen
What makes a good antigen?
to initiate an immune response, a substance must be large enough to “catch the attention” of surveillance cells large
Complex macromolecules of 100,000 Daltons are the most immunogenic
-size alone isnt sufficient for antigenicity
-highly repetitious structures are not immunogenic
Presentation of antigens
cell engulfs microbe into vesicle –> breaks bacteria into smaller components –> components then attached w/MHC II receptors and transported to the membrane (the heart of the pathogen) for presentation to Helper T cells (present it on the outside)
once presented antigen is bound the the MHC and T cell receptor (which is specific to that particular antigen) –> the helper T cell is activated
The activated helper T cell in antigen presentation
the activated helper T cell is a central control point for all T-cell immunity, and most of B-cell immunity
most antigens must be presented first to T cells, even though they will eventually activate both the T-cell and B-cell systems
T cell antigen response: Cell-mediated immunity (CMI)
when an antigen is detected, a T-cell will differentiate into one of the following:
- helper T cells
- memory T cells
- regulatory T cells
- cytotoxic T cells
Memory T cells
remembers the antigen for future attacks by this pathogen
Regulatory T cells
control the T cell response
Cytotoxic T cells
lead to the destruction of infected host cells and other “foreign” cells
kill our infected cells
Helper T cells
activate macrophages, assist B-cell processes and help activate cytotoxic T cells
APC reaction w/a helper T cell
once the helper T cells are activated by the MHC/antigen complex, the helper T cell will differentiate into one of many cells that will:
- activate B cell
- stimulate macrophages
- increase inflammation, etc
APC reaction w/a CD8 T-cell
once the CD8 T-cells are activated by the MHC/antigen complex, these cells will differentiate into Cytotoxic T cells that can kill viral infected cells, cancer cells, and cells from other animals or humans
notice the infected host cell –> release cytotoxic T cells to kill those infected host cells
THE IMPORTANT THINGS TO KNOW FROM T CELL RESPONSE:
T-CELL RESPONSE IS CELL-MEDIATED IMMUNITY
helper T-cells are activated by APC Activated helper T-cells then differentiate into a # of different types of T-cells --> these cells can: -activate B cells -stimulate macrophages -cause inflammation -or regulate the T-cell immune response
CD8 T-cells: activated by APC Activated CD8 cells differentiate into Cytotoxic T-cells that kill: -viral infected cells -cancer cells -cells from other animals or humans
Stages III and IV: Antigen challenges B-cells (III) and B-cell response (IV)
at the same time the T-cell system is being activated, B-cells are being activated too
B-cell antigen response: Release of antibodies
When activated, B cells divide and give rise to:
-plasma cells
-memory B cells
Plasma cells: release antibodies into the tissue and the blood
Antibodies: attach to the antigen for which they are specific, and the antigen is marked for destruction or neutralization
B cell response: Antibody functions
opsonization
neutralization
agglutination
complement fixation
Opsonization
antigen is “coated” with antibody and phagocytosis is enhanced
Neutralization
antibodies bind to antigen and prevent the antigen from binding to its target
Complement fixation
Tags cell for lysis
Immunological memory
antibody titer
primary response
secondary response
Secondary response
aka memory
immune response intensifies after second exposure to antigen
total antibody level produced during secondary response is much greater than the primary response
Natural immunity (specific)
any immunity that is acquired thru the normal biological experiences of an individual
can be active or passive
using your immune system to treat yourself, or for women, their children
Artificial immunity (specific)
protection from infection obtained thru medical procedures such as vaccines and immune serum
can be active or passive
Active: vaccines
Passive: immunoglobulin
Active immunity
when an individual receives immune stimulus (antigen) that activates B- and T-cells to produce immune substances such as antibodies
Creates memory that renders the person ready for quick action upon re-exposure to the same antigen
Requires several days to develop after antigen exposure
Lasts for a relatively long time (memory cells)
Can be stimulated by natural or artificial means
Passive immunity
Occurs when an individual receives antibodies from another human or animal
Recipient is protected for a short period of time, even though they have not had prior exposure to the antigen
Lack of memory for the original antigen
Immediate onset of protection
Short-term effectiveness
Can be natural or artificial in origin
Basic principles behind vaccination
Stimulate a primary response and a memory response so that the next time your body comes in contact with this pathogen it has memory of it
Prime the immune system for future exposure to a virulent pathogen
If the pathogen enters the body, the response will be immediate, powerful, and sustained because the immune system now has memory of that antigen
Immunoglobulin treatment
First attempts involved the transfusion of horse serum containing antitoxins to prevent tetanus and treat diphtheria
Antisera from animals has now been replaced with human products, or genetically engineered products
gamma globulin
Gamma globulin
Immunoglobulin extracted from the pooled blood of many human donors
Used to treat specific infections in high-risk neonates and other immunocompromised patients
Useful when there is no effective treatment available or to treat immune deficiencies
DNA vaccines
Microbial DNA is inserted into a plasmid vector and inoculated into a recipient
Human cells will take up some of the plasmids and express the microbial DNA in the form of proteins
These foreign proteins will be recognized during immune surveillance, and cause B- and T-cells to be sensitized and form memory cells
Experiments with animals have shown that these vaccines are very safe
Any number of microbial proteins can be expressed, making the stimulus more complex
Vaccine side effects
Vaccines must go through years of trials in experimental animals and human volunteers before they are licensed for general use
Still some complications occur local reactions at the injection site
-fever
-allergies
-other adverse reactions
Stages of the third line of defense
- lymphoctyte development and differentiation
- the presentation of antigens
- the challenge of B & T lymphocytes by antigens
- T-lymphocytes response: cell mediated immunity, and B lymphocyte response: the production and activities of antibodies
2 important features of clonal selection
- lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the tissues
- each genetically distinct lymphocyte expresses only a single specificity and can react to only one type of antigen
Killed/inactivated whole cell vaccines
prepared by cultivating the desired strain(s) of a bacterium or virus, treating them w/chemicals, radiation, heat or some other agent that doesn’t destroy antigenicity
Live, attenuated cell vaccine
Virus vaccine
contain live microbes whore virulence has been lessened/eliminated
usually achieved by modifying the growth conditions or manipulating microbial genes in a way that eliminates virulence factors
