Chapter 13 Flashcards
Adaptive immunity is initiated in secondary lymphoid tissues
- Lymph carries antigens and infected cells (DCs) to lymph node through afferent vessel.
- B and T cells in lymph node become activated upon encountering antigens.
- B and T cells mature into effector cells with specific functions, such as antibody production from B cells.
- Macrophages residing in lymph nodes filter out antigens and pathogens from lymph to protect blood.
- Lymph fluid and lymphocytes exit through efferent vessel
Adaptive immunity: the third and final line of defense
• Adaptive immunity acquired only after an immunizing event such as an infection
• B and T lymphocytes undergo a selective process that prepares them for reacting only to one specific antigen or immunogen
• Immunocompetence: the ability of the body to react with countless foreign substances
Immunocompetence
The ability of the body to react with countless foreign substances
Antigen
Molecules that can be seen and indemnified by the immune system
Antigens and immunogens
Antigens: molecules that can be seen and identified by the immune system
• If they provoke a response, they are called immunogens
• Protein or polysaccharide molecules on or inside cells and viruses
• Any exposed or released protein or polysaccharide is potentially an antigen, even those on our own cells:
• Our own antigens usually do not evoke a response from our own immune system
Specificity
Antibodies are produced against the chickenpox virus and will not function against the measles virus
Memory
Lymphocytes have been programmed to “recall” the first engagement with the invader and rush to the attack once again
Stages of immunologic development and interaction
I. Lymphocyte development and clonal deletion
II. Presentation of antigen and clonal selection
- antigen presents and the selection for what reacts with that antigen is completed
III. Challenge of B and T lymphocytes by antigens
IV. T-lymphocyte response: cell-mediated immunity; and B-lymphocyte response: production and activities of antibodies
Lymphocyte development
• All lymphocytes arise from the same basic stem cell type
• Both cell types migrate to separate areas of lymphoid organs -> dependent on where they are needed
• B and T cells constantly recirculate through the circulatory system and lymphatics, migrating into and out of the lymphoid organs
Entrance and presentation of antigens and colonial selections
When pathogens carrying antigens cross the first line of defense:
• Resident phagocytes migrate to the site
• Tissue macrophages ingest the pathogen and initiate an inflammatory response
• Dendritic cells ingest the antigen and migrate to the nearest lymphoid organ, where they process and present antigen to T and B lymphocytes
• Gamma-delta cells can be activated by PAMPs
Role of markers and receptors in presentation and activation
All cells have a variety of different markers on their surfaces for:
• Detection
• Recognition
• Cell communication
These markers play an important role in activating different components of immunity
Role of markers and receptors in presentation and activation
MHC
HLA
Major histocompatibility complex (MHC): one set of genes that codes for human cell markers or receptors:
• Gives rise to a series of glycoproteins found on all cells except red blood cells
• Also called the human leukocyte antigen (HLA) system
• These markers play a vital role in recognition of self by the immune system and in rejection of foreign tissue
Three classes of MHC genes
- Class I genes: code for markers that appear on all nucleated cells. They display unique characteristics of self and allow for the recognition of self molecules and the regulation of immune reactions. The system is rather complicated in its details, but in general, each human being inherits a particular combination of class I MHC (HLA) genes in a relatively predictable fashion
• Class II genes: also code for immune regulatory markers. These markers are found on macrophages, dendritic cells, and B cells and are involved in presenting antigens to T cells during cooperative immune reactions
• Class III genes: encode proteins involved with the complement system, among others
CD molecules
CD: “cluster of differentiation”:
• Over 400 CD molecules have been named
• Many are involved in the immune response
Most important CDs:
• CD3
• CD4
• CD8
Lymphocytes receptors
- major role is the “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 with MHC molecules on the presenting surface
- there are potentially millions and even billions of unique types of antigens
How to challenge B and T cells with antigens
- when challenges with antigens, both B and T cells proliferate and differentiate
- a clone, or a group of genetically identical cells, are created
- some clones are memory cells that will ensure the future reactiveness against a specific antigen
- B and T cell responses differ
The three functions of T cells
Helper T cells
Regulatory T cells
Cytotoxic T cells
Helper T cells
Activate macrophages, assist B-cell processes, and help activate cytotoxic T cells
Regulatory T cells
Control the T-cell response by secreting anti-inflammatory cytokines or preventing proliferation
- the ability to do enough by not too much
- to kill but not stand out
Cytotoxic T cells
Lead to the destruction of infected host cells and other “foreign” cells
T cells secrete?
T cells secrete cytokines to help destroy pathogens, but they DO NOT produce antibodies
How do B cells respond to antigens
- when activated, B cells divide and give rise to plasma 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 from destruction of neutralization
B cells
Site of maturation: Bone marrow
Specific surface markers: immunoglobulin
Circulation in blood: low numbers
Receptors for antigens: B-cell receptor (immunoglobulin)
Distribution in lymphatic organs: cortex (in follicles)
Does it require antigens presented with MHC: no
The product of antigenic stimulation: plasma cells and memory cells
General functions: production of antibodies to inactivate, neutralize, target antigens
T cells
Site of maturation: thymus
Specific surface markers: T-cell receptor -> several CD molecules
Circulation in the blood: high numbers
Receptors for antigens: t-cell receptor
Distribution in lymphatic organs: paracoritcal sites (interior to the follicles)
Does it require antigen presented with MHC: yes
Product of antigenic stimulation: several types of activated T cells and memory cells
General functions: cells activated to help other immune cells; suppress or kill abnormal cells; mediate hypersensitivity; synthesize cytokines
What are some specifics events in T-cell development
• Maturation of T cells and development of their receptors is directed by the thymus gland and its hormones
• CD3 receptors: surround the T-cell receptor and assist in binding
• CD4 coreceptors: accessory receptor proteins that helps the T-cell receptor bind to MHC class II molecules
• CD8 coreceptors: found on cytotoxic T cells and helps bind MHC class I molecules
What are some specifics events in B-cell development
• Develop in the bone marrow
• Naïve lymphocytes circulate in the blood, “homing” to specific sites in the lymph nodes, spleen, and other lymphoid tissue, where they adhere to specific binding molecules and come into contact with antigens throughout life
How to build immunologic diversity
By the time B and T cells reach lymphoid tissues, each one is equipped to respond to a single unique antigen
Diversity is generated by rearrangement of gene segments that code for antigen receptors on T and B cells:
• Every possible recombination occurs, leading to a huge assortment of lymphocytes
• It is estimated that each human produces antibodies with 10 trillion different specificities
immunoglobulin (Ig)
- large glycoprotein molecules that serve as the antigen receptors of B cells
- serve as antibodies when secreted
what is the structure of immunoglobulin
- antigen binding sites
- variable (V) regions
- antigen binding sites -> pockets in the ends of the forks the molecules that can be highly variable in shape so that they can fit a wide range of antigens
- variable (V) regions -> areas of extreme versatility from one clone to another
- light chains, heavy chains, constant (c) regions: amino content does not vary greatly from one antibody to another
T-cell receptors
belong to the same protein family as the B-cell receptors
similar to B cells:
- formed by genetic modification
- have variable and constant regions
- inserted into the membrane
- have an antigen binding site
relatively small and never secreted
clonal selection
- the mechanism by which the exactly correct B or T cell is activated by any incoming antigen
- lymphocyte specifically is preprogrammed, existing in the genetic makeup before an antigen has ever entered the tissues
- each genetically distinct lymphocyte expresses only a single specifically and can react to that chemical epitope
clonal deletion
- one potentially problematic outcome of random genetic assortment is the development of clones of lymphocytes able to react to self:
- can lead to severe damage
Clonal deletion: process by which any such clones are destroyed during development
clonal selection and deletion steps
Each genetically unique line of lymphocytes that arises from extensive recombination’s of surface proteins is termed a clone. This stage of lymphocyte development does not require the actual presence of foreign antigens.
At the same time, any lymphocytes that develop a specificity for self molecules (and could be harmful) are eliminated from the pool of cells. This is called clonal deletion and leads to immune tolerance.
The specificity for a single epitope is programmed into the lymphocyte and is set for the life of a given cell. The end result is an enormous pool of mature but naive
lymphocytes that are ready to further differentiate under the influence of certain immune stimuli.
When any epitope enters the immune surveillance system, it encounters specific lymphocytes ready to recognize it. This stimulates activation of that clone,
leading to genetic changes that cause it to differentiate into an effector cell. Mitotic divisions then expand it into a larger population of lymphocytes, all bearing the same specificity. This is clonal expansion.