Immunology I Flashcards
What is immunology?
Functions:
-Protection from microbial pathogens
-Protection from “foreign” cells that may have malignant potential
-Detected damaged tissue and facilitates regeneration or repair of those tissues
Permits microflora to aid in:
-Protection
-Provision of nutrients
Components of the immune system:
-A widely diversity of cells derived from the bone marrow and that are relatively free to circulate through the body
-Discrete, unique and widely-distributed lymphatic system
-A wide diversity of molecular signals and effectors that are relatively free to circulate throughout the body
Disorders of the immune system:
-Allergy and autoimmune disease (immune-mediated diseases)
-Acute and chronic inflammatory states (outside of immune-mediated diseases)
-“Bystander” damage that happens when attacking a pathogen
Overview of immune response:
1) Recognize foreign molecules, microbes, or cells
2) Destroying foreign molecules, microbes, or cells
-Often by disrupting cell membranes, using free radicals to damage cellular components, or enzymatically catalyzing degradation of cellular components
-That which cannot be destroyed is often isolated from the rest of the body
3) Communicating between these two activities
Two major funcional divisions of immune system:
1) Innate immunity: 1st line of defense
2) Adaptive imunity-activated when innate defenses are breached (delayed)
Innate immunity:
“1st line of defense”
Features cellular and molecular effectors that are either:
-Less specific: each cell or molecule recognizes a range of targets
-Genetically “hard-wired”: cells and molecular effectors don’t change during the lifespan of the organism
Adaptive immunity:
Activated when innate defenses are breached (delayed).
Features cellular and molecular effectors that are:
-Highly specific: each cell or molecule recognizes a particular target
-Genetically “changeable”: cells and molecular effectors change their germline DNA to produce unique receptors/effectors during the lifespan of the organism
Specificity of adaptive immunity:
Recognition of a foreign molecule by high-affinity binding to a receptor:
-The affinity can increase as the receptor is modified over time
-Receptors are generated by genetic recombination (gene shuffling) particular portions of the receptors
Antigen:
-A substance that can bind to a receptor of the adaptive immune system
-Receptors include B-Cell and T-cell receptors
-B-cell receptors can be released from a B-cell into the ECF=> antibody
Immunogen:
A substance that can generate an adaptive immune response.
Hapten:
A substance that can bind to an antibody, but CANNOT generate an immune response.
Often haptens are “too small” to activate the receptor.
Epitope:
The molecular entity that binds to a receptor.
This antigen displays multiple different epitopes-note the different antibody affinities.
-There were all produced by different B-lymphocytes
Diversity of adaptive immunity:
Vertebrate immune system can recognize 10^16 distinct antigens.
This is accomplished by sets of corresponding recognition molecules (receptors) on immune cells.
-B cell receptors
-T cell receptors
No two naive T or B cells are activated by the same molecule.
Diversity is accomplished by randomly “shuffling” portions of genes for lymphocyte receptors and selecting receptors that:
-are functional
-Do not recognize self
Lymphocyte receptor repertoire:
The set of antigens (Ag) receptors in a given individual’s immune system
Clonal Selection Theory:
Each lymphocyte bears a single type of receptor with a unique specificity
Receptor binding is required for cell activation
The differentiated effector cells derived from an activated lymphocyte bear receptors of identical specificity as the parent cell.
-They are clones of the parent cell: exact genetic copies with the same receptor
Those lymphocytes bearing receptors for self molecules (ex: endogenous antigens produced within the body) are destroyed at an early stage.
-We select functional receptors that do not bind to self
B-Cell receptor:
Naive B-cells express Ab on their surface, where they are called B cell receptors
Once activated, B cells secrete Ab’s into the blood (aka immunoglobulins-Igs)
B cell receptors:
Light chains (2) & heavy chains (2):
Each with variable and constant regions:
-The variable regions are the portions that are “shuffled” and that can bind to antigen
Some antigens can be bound by many different antibodies:
-Different epitopes on the same antigen
B cell receptor antigens:
Most antibodies bind to protein antigens-distinct sequences of amino acids:
Recognized amino acid sequence can be either:
-Continuous (linear)
-Discontinuous (conformational)
Antibodies can also bind to lipid, nucleic acid, and carbohydrate moieties:
-A wide range of molecules can be recognized.
T cell receptor:
Structurally very similar to the Fab portion of Ab
2 chains: 1 alpha, 1 beta-each with a variable (V) region and a constant (C) region
Best at recognizing protein antigens
The T-cell receptor is never secreted-it always stays attached to the membrane
T cell receptors only recognize antigen by:
Close communication with molecules on other cells:
-Known as antigen presentation
-Never bind to antigen “just floating around” dissolved in the ECF
Adaptive immunity memory:
Exposure of the adaptive immune system to an antigen increases its ability to respond to the same or closely related antigen following re-exposure
Secondary immune responses are generally:
-faster
-larger
-Qualitatively different and often involve relatively high-affinity B-cell receptors
How could you explain memory in context of clonal selection theory?
Antibodies are created so the next time this is encountered it is a quick process.
The affinity of the receptors to the antigens improves throughout the reaction.
Adaptive and innate immunity:
Self-limiting:
Both adaptive and innate responses are transient:
-The methods of downregulating the immune response differ greatly between the innate and adaptive immune system…but they can also interact
Immune responses are tightly regulated and controlled:
-Control and down regulation of the adaptive immune system is often quite specific, as is activation
Adaptive and innate immunity:
Self/Non-self discrimination:
The immune system must distinguish self from non-self:
-Immune responses to self can result in autoimmunity
-Immunological unresponsiveness to self= tolerance
Immature:
A cell that has not reached a point where it can become activated- usually refers to cells of the adaptive immune system.
Naive:
A mature cell that has not yet been activated-always refers to adaptive immune system.
Activated or Effector:
A cell (or group of cells) that is currently an active participant in an immune response.
Anergic:
A cell that responds to receptor binding by deactivation of the cell-it “goes to sleep”
Clone:
A group of effector T/B cells that express the same antigen receptor and are derived from the same parent cell.
Cells & tissues of the immune system:
-Myeloid cells
-Lymphoid cells
-Primary lymphoid cells
-Secondary lymphoid cells
Myeloid cells:
Granulocytes:
-Neutrophils
-Basophils
-Eosinophils
-Mast cells
Monocytes:
-Macrophages
Dendritic cells
(RBC’s & platelets)
Lymphoid cells:
T cells
B cells
NK cells
Dendritic cells
Monocytes/macrophages:
Myeloid progenitor cells:
-Monocytes circulate in the blood & differentiate into macrophages upon migration into tissue (long-lived)
-Macrophages are phagocytic, and are the mature form of monocyte
-Macrophages often produce soluble messengers that help orchestrate a wide range of adaptive and innate immune responses
Present antigens to T cells
Dendritic cells:
Myeloid progenitor cells:
-Resident int he body’s tissues
-During infection, recognizes infection and transports antigen to lymphoid organs
-Present antigens to T-cells-Important in T cell activation during adaptive immune responses.
Granulocytes:
Neutrophils:
-Phagocytic and enter sites of infection (short-lived)
-Die in infected tissues => form pus (purulent inflammation)
-Most numerous cellular components of innate immune system
Granulocytes:
Eosinophils:
-Defense against parasites
-Involved in hypersensitivity responses
Granulocytes:
Basophils:
-Along with mast cells, protect mucosal body surfaces & release histamine in hypersensitivity responses
-Also implicated in defense against parasites
Mast cells:
-reside in all connective tissues: only resident granulocyte and have a unique role
-Orchestrate hypersensitivity responses (ex) seasonal allergies), important in mucosal immune responses
Lymphoid progenitor:
B-cells:
-Bone marrow derived
-Upon activation, differentiate into Ab-secreting plasma cells
Lymphoid progenitor:
T-cells:
-Thymus-derived (though originate in bone marrow)
Become either helper T cells (Th) or cytotoxic T lymphocytes (CTL):
-Helper T (Th) cells: Activate other cells (macrophages, B cells)
-Cytotoxic T cells (CTLs): Kill cells that express foreign molecules
T and B cells look alike, each having receptors for specific antigen
Lymphoid progenitor:
NK cells:
-Important in the innate immune system
-Lack antigen-specific receptors
-Kill infected & altered cells (ex: malignant cells)
“Adaptive” & “Innate” cells: a caveat:
Some texts artificially categorize immune cells as being “adaptive” or “innate” cells based on the specificity of the cell’s receptor/effector.
- In this categorization, only lymphocytes are “adaptive”
However:
-Dendritic cells and macrophages are absolutely key in presenting antigens to T-lymphocytes.
-Many “innate? immune cells produce cytokines that inform helper T-cells about how to “help” other immune cells.
-Certain subsets of helper T-cells are dedicated to ONLY aiding innate immune responses
-Mast cells, neutrophils, eosinophils, and macrophages are important at helping to clear antigens that are bound by antibody.
Lymphoid tissues:
-Organized tissues where lymphocytes interact with non-lymphoid cells
-Important in initiation/maturation of adaptive immune responses
2 types of lymphoid tissues:
-Primary (central) lymphoid organs
-Secondary (peripheral) lymphoid organs
Primary lymphoid organs:
-Where lymphocytes ae generated and mature
Includes bone marrow & thymus:
-Both B and T cells are generated in the bone marrow
-B cells mature in the bone marrow
-T cells mature in the thymus
Once lymphocytes mature they leave primary lymphoid organs and are capable or responding to an antigen
Secondary Lymphoid organs:
Where adaptive immune responses are initiated-antigens and B/T cells receptors encounter each other.
-Exist to bring antigen and lymphocytes together
(lymph nodes, spleen, and MALT)
Lymph node (LNs):
Lie at junctions of lymphatic vessels.
Collect extracellular fluid (lymph) and return it to the blood (via lymphatics)
Afferent lymphatics drain lymph and antigens from tissues, carrying it to the nodes where antigen is trapped.
Spleen:
Fist-sized organ located deep and lateral to the stomach
Filter for blood-collects blood-borne antigens & also destroys aged RBC’s
B-cells in the spleen produce large quantities of antibodies and secrete them into the blood stream:
-Most B-cells undergo some degree of maturation in the spleen
Organ is divided into red pulp & white pulp:
-Red pulp: where old RBCs are destroyed
-White pulp: Where lymphocytes surround arterioles entering organ: further subdivided into corona and periarteriolar lymphoid sheaths (PALS)
Mucosa-associated lymphoid tissue (MALT):
Includes gut- and bronchial-associated lymphoid tissues (GALT, BALT, etc…)
Purpose is to collect Ag from mucosal surfaces
Specialized lymphoid tissue at the body’s “wet” surfaces required due to large surface area, rich with potential pathogens
GALT:
Includes tonsils, adenoids, appendix and Peyer’s Patches (PP)
PPs collect Ag from epithelial surfaces of GI tract via M cells
PPs composed of distinct T and B cell areas
