immune system Flashcards
Adaptive Immune Response
Ability to specifically recognize and make a response against a wide variety of pathogens.
Antigens, the small chemical groups often associated with pathogens, are recognized by receptors on the surface of B and T lymphocytes.
Primary vs. secondary immune response and immunological memory
Primary adaptive response - the immune system’s first exposure to a pathogen. Sx of a first infection, called primary disease, are always relatively severe
Secondary adaptive response - upon re-exposure to the same pathogen, a secondary adaptive immune response is generated, which is stronger and faster that the primary response and often eliminates a pathogen before it can cause significant tissue damage or any symptoms.
Immunological memory - protects us from getting diseases repeatedly from the same pathogen. By this mechanism, an individual’s exposure to pathogens early in life spares the person from these diseases later in life.
Self recognition
The adaptive immune system has the ability to distinguish between self-antigens, those that are normally present in the body, and foreign antigens, those that might be on a potential pathogen.
T-cell mediated responses
at the T cell level
T lymphocytes recognize antigens based on a two-chain protein receptor.
alpha-beta T cell receptors have 2 domains
variable region domain: furthest away from the T cell membrane. its amino acid sequence varies between receptors.
constant region domain has less variation.
Each T cell produces one type of receptor and thus is specific for a single particular antigen.
Antigens & Antigen presenting cells
T cells only recognize antigen on the surface of specialized cells called antigen-presenting cells.
Antigens are internalized by these cells. Antigen processing is a mechanism that enzymatically cleaves the antigen into smaller pieces.
The antigen fragments are then brought to the cell’s surface and associate with an antigen-presenting protein known as a major histocompatibility complex (MHC) molecule. The association of the antigen fragments with an MHC molecule on the surface of
a cell is known as antigen presentation (chemical basis of specificity) and results in the recognition of antigen by a T cell.
MHC Classes - which MHC relates to which types of cells
MHC class I -
Many cell types present MCH class 1 for intracellular antigens. stimulates cytotoxic T cell immune response, destroying the cell and the pathogen. Viruses infect nearly every tissue of the body, so all these tissues must be able to express class I MHC or no T cell response can be made.
MHC class II -
expressed only on the cells of the immune system, specifically cells that affect other arms of the immune response. aka “professional”
antigen-presenting cells. The three types of professional antigen presenters are macrophages, dendritic cells, and B cells
dendritic cells (DCs)
Dendritic cells also kill pathogens by phagocytosis but their major function is to
bring antigens to regional draining lymph nodes. The lymph nodes are the
locations in which most T cell responses against pathogens of the interstitial tissues are mounted.
macrophages located in…
Macrophages stimulate T cells to release cytokines that enhance phagocytosis. skin and in the lining of mucosal surfaces, such as the nasopharynx, stomach, lungs, and intestines.
B cells fx
B cells may also present antigens to T cells, which are necessary for certain types of antibody responses
- internalize antigens via BCRs
- express MHC class 2 molecules
- express co-stimulatory molecules following activation
DCs and macrophages commonalities
- phagocytic
- express receptors for apoptotic cells DAMPs and PAMPs
- express MHC class 2 molecules
- localize to tissues
- localize to t cell zone of lymph nodes once activated (DCs)
- express co-stimulatory molecules following activation
T Cell Development and Differentiation
T cell tolerance - eliminating T cells that might attack the cells of one’s own body
2) 1) In cortex of thymus
“Double negatives” - thymocytes in the cortex of the thymus that do not bear CD4 or CD8 molecules
Positive selection - thymocytes exposed to cortical epithelial cells; double-negative thymocytes bind to the MHC molecules they observe on the thymic epithelia, and the MHC molecules of “self” are selected.
This mechanism kills many thymocytes during T cell differentiation. 2% of the thymocytes leave as mature, functional T cells.
2) Junction of cortex and medulla of thymus
The cells become “double positives” that express both CD4 and CD8 markers and move from the cortex to the junction between the cortex and medulla
3) In the thymic medulla
Negative selection - self-antigens are brought into the thymus from other parts of
the body by professional antigen-presenting cells. The T cells that bind to these
self-antigens are selected for negatively and are killed by apoptosis.
The only T cells left are those that can bind to MHC molecules of the body with
foreign antigens presented on their binding clefts, preventing an attack on one’s own body tissues, The cells that leave the thymus become single positives, expressing either CD4 or CD8, but not both. The CD4+ T cells will bind to class II MHC and the CD8+ cells will bind to class I MHC.
T Cell Mediated Responses - clonal expansion vs. clonal selection
Clonal expansion - mature T cells become activated by recognizing processed foreign antigen in association with a self-MHC molecule and begin dividing rapidly. necessary to make the immune response strong enough to effectively control a
pathogen.
Clonal selection - process of antigen binding only to those T cells that have receptors specific to that antigen. Each T cell that is activated has a specific receptor “hard-wired” into
its DNA, and all of its progeny will have identical DNA and T cell receptors, forming clones
of the original T cell.
Cellular basis of immunological memory
During a primary adaptive immune response, both memory T cells and effector T cells are generated.
**Memory T cells **
long-lived and can even persist for a lifetime. primed to act rapidly. Thus, any subsequent exposure to the pathogen will
elicit a very rapid T cell response.
This rapid, secondary adaptive response generates large numbers of effector T cells so fast that the pathogen is often overwhelmed before it can
cause any symptoms of disease. This is what is meant by immunity to a disease.
T Cell types and functions - Helper T cells, Cytotoxic cells, Tregs
Helper T Cells (Th) - bearing the CD4 molecule, function by secreting cytokines that act to enhance other immune responses. T cell help is required for antibody responses to most protein antigens (T cell-dependent antigens).
Th1 cells - regulate immunological activity and
development of cells, incl. macrophages, other T cells.
Th2 cells - act on B cells to drive their differentiation into plasma cells that make antibody.
Cytotoxic T cells (Tc) - T cells that kill target cells by inducing apoptosis using the same mechanism as NK cells. More Tc cells forming will overwhelm the ability of the virus to cause disease.
Regulatory T cells (Treg), or suppressor T cells: bear the CD4 molecule and suppress other T cell immune responses.
What is an antibody?
Antibodies are glycoproteins consisting of two types of polypeptide chains with attached carbohydrates.
An antibody protein is a secreted form of a B cell receptor.
There are five different classes of antibody found in humans:
IgM, IgD, IgG, IgA, and IgE.
Each of these has specific functions in the immune
response
