Adaptive immune response Flashcards
Nature of Antigens
Coined from compounds that elicit antibody production
– ANTIbody GENerator (ANTIGEN)
– Includes an enormous variety of materials
– Today, term used to describe any compound that elicits an immune response
– Antigen that causes immune response termed immunogen
– Proteins and polysaccharides induce string response
* Lipids and nucleic acids often do not
– Recognition of antigen directed at antigenic determinant or epitope
Structure of the Ab
– Basic unit is the monomer
– Made of four chains of amino acids held together by disulfide bonds
– Two chains are heavy
– Two chains are light
– Each heavy and light chain has a constant region. The constant region is known as Fc region
– Each heavy and light chain has a variable region
* Variable region is unique to each Ab. This region binds to a specific Ag and is known as “Fab” region
What are the protective outcomes of antibody-antigen
binding?
– Neutralization
– Immobilization and prevention of adherence
– Agglutination and precipitation
– Neutralization: Prevents toxin from interacting with
cell
– Immobilization and prevention of adherence: Antibody bonding to cellular structures to interfere with function
– Agglutination and precipitation: Clumping of bacterial cells by specific antibody. Bacteria more easily phagocytized
Protective outcomes of antibody-antigen binding
– Opsonization
– Complement activation
– Antibody-dependent cellular cytotoxicity
– Opsonization: Coating of bacteria with antibody to
enhance phagocytosis
– Complement activation: Antibody bonding triggers classical pathway
– Antibody-dependent cellular cytotoxicity: Multiple antibodies bind a cell which becomes target for certain cells
Ab divided into five classes
– Class is based on constant region of the Ab
– Classes include:
IgG IgA IgM IgD IgE
IgM is?
– First Ab to respond to infection
– 5 – 13% of Ab in circulation
– Structure: pentamer
– Five monomer units joined together at the constant region
– Found on the surface of B lymphocytes as a monomer
– Only Ab that can be formed by the fetus
IgG is
–Dominant Ab in circulation – 80 – 85% Ab in circulation – Structure = monomer – Only Ab that can cross the placenta – The antibody of memory!!!!!
IgA
– Found in secretions – 10 - 13 % of Ab in circulation – Structure * Monomer in serum * Dimer in secretions – Breast milk, mucus, tears and saliva
IgD
Structure = monomer
Maturation of antibody response
IgE
– Barely detectable in circulation
– Structure = monomer
– Active in allergic reaction
Lymphoid system collection of tissues and organs designed to?
Bring B and T cells in contact with antigens
– In order for body to mount appropriate response, immune cells must encounter antigen
Lymphoid system includes
– Lymphatic vessels
– Secondary lymphoid organs
– Primary lymphoid organs
Lymph travels through vessels to lymph nodes. Material such as?
Protein is removed
– Fluid portion empties back into blood stream
Primary lymphoid organs
– Bone marrow and thymus are primary lymphoid organs.
Location where stem cells destined to become B and T
cells mature
– B cells mature in bone marrow
– T cells mature in thymus
Once mature, cells leave primary lymphoid organs and
migrate to secondary lymphoid organs
Secondary lymphoid organs
– Sites where lymphocytes gather to encounter antigens; organs include:
* Lymph nodes
* Spleen
* Tonsils
* Adenoids
* Appendix
– Organs situate strategically: Allows for initiation of immune response from nearly any place in body
During lymphocyte development, B and T cells acquire ability to recognize distinct epitopes
– Once committed to specific antigen, cells “checked
out” to ensure proper function
– B cells undergo developmental stages in bone marrow
– T cells go through process in thymus
When antigen introduces into body, only appropriate
antibody bonds
– Initiates multiplication of specific antigen
* Process called clonal selection
* Repeated cycles of cell division generates population
of copied antibodies. Termed clonal expansion
– Without sustained stimulation, cells undergo apoptosis
Lymphocyte characteristics include
– Naïve: Have antigen receptor but have not encountered antigen
– Activated: Able to proliferate> Have bound antigen
– Effectors: Descendants of activated lymphocytes. Able to produce specific cytokines. Plasma cells, T helper and cytotoxic T cells effector cells
– Memory lymphocytes: Long-lived descendants of activated lymphocytes. Memory cells responsible for seed and effectiveness of secondary response. Remembers antigen on subsequent exposure
First response to particular antigen called primary response
– May take a week or more to develop
– Immune system remembers pathogen on subsequent
exposure: Termed secondary response
– Adaptive immunity divided into:
*Humoral immunity: Eliminates extracellular pathogens
* Cellular immunity: Eliminates intracellular pathogens
Overview of humoral immunity
– Mediated by B lymphocytes a.k.a B cells
– Develops in bone marrow
– B cells may be triggered to proliferate into plasma
cells
– Plasma cells produce antibodies
– Antibodies produce when antigen binds B cell receptor
– Some B cells produce memory cells
Overview of cellular immunity
– Mediated by T lymphocytes a.k.a T cells
– Matures in thymus
– Divided into 2 subsets
1) Cytotoxic T cells
2) Helper T cells
– T cell receptors help with antigen recognition
Legionella has molecules in the cell wall that bind and uses C3b receptors to invade macrophages. This does what?
Prevents active phagocytosis by macrophages.
When Chlamydia invades phagocytic cells, the bacteria prevents the formation of phagolysossomes, and
therefore Chlamydia can?
Avoid been digested
A human host can prevent a pathogen from getting enough iron by?
a. Binding iron with Transferrin
b. Binding iron with Lactoferrin
c. Binding iron with Hemoglobin
Decrease in the production of C3 would result in
Increased susceptibility to infection
Helicobacter pylori uses the enzyme urease to counteract a chemical defense in the human organ in which it
lives. This chemical defense is:
Hydrochloric acid
Antibodies that protect the fetus and newborn
IgG
The first antibodies to be synthesized , especially effective against microorganisms
IgM
Antibodies that are bound to Mast cells and involved in allergic reactions.
IgE
Antibodies that protect mucosal surfaces.
IgA
A variety of drugs with the ability to reduce inflammation are available. Comment on the danger of misuse of
these anti-inflammatory drugs.
Inflammatory reactions are needed not only for the control of infectious agents but to induce healing and replacement of damaged tissue. Misuse of anti-inflammatory drugs can disturb these processes.
Leukocyte adherence deficiency (LAD) is an inherited disease resulting in the inability of neutrophils to recognize
C3b-bound microorganisms. What are the most likely consequences of LAD?
LAD leukocytes can’t recognize opsonized microorganisms, which delays the elimination of the
microorganism by innate response and increases the susceptibility to infection.
A Hematologist often performs a differential white blood cell count on a blood sample. Such a count determines
the relative numbers of white blood cells. Why are these numbers important? What do you think a hematologist
would find in a differential with blood cell count of a patient with mononucleosis? With Neutropenia? With
eosinophilia?
Differential blood count is a snap shot of one’s immune system.
With mononucleosis we would expect a drop on the number of B cells in the first phase of the infection.
Neutropenia or low number of neutrophils results in susceptibility to infection. Neutrophils are the first line of
defense in the immune response.
Eosinophilia, increased eosinophils usually indicate allergy or parasitic infection.
How does a T cell recognize an Antigen?
T cells only recognize antigens inside a molecule of MHC
Explain why a person who recovers from a certain disease can attend others with the same disease without fear
of contracting it
Memory is the key for secondary responses, which are faster and more efficient than primary responses.
Memory to a antigen explains why, even when in contact with the pathogen, an individual that had been
exposed to a pathogen will have less chance to develop the same disease again, and therefore can attend
others with the same disease.
Explain what an antigen is. Distinguish an antigen from a hapten.
Antigen is an antibody generator - any molecule that can trigger the production of antibodies.
Haptens are incomplete antigens, they need a carrier protein in order to induce the production of antibodies,
usually haptens are to small to fit the MHC on their own.
B Lymphocytes (B Cells) and Antibodies – Classes of antibodies
– IgM–first antibody produced
– IgG–most common and longest-lasting antibody
– IgA–associated with body secretions
– IgE–involved in response to parasitic infections and
allergies
– IgD–exact function is not known
The Roles of the Major Histocompatibility
Complex
– Group of antigens first identified in graft patients
– Important in determining compatibility of tissues for
tissue grafting
– Major histocompatibility antigens are glycoproteins
found in the membranes of most cells of vertebrate
animals
– Hold and position antigenic determinants for
presentation to T cells
The Roles of the Major Histocompatibility
Complex
– Antigens bind in the antigen-binding groove
of MHC molecules
– Two classes of MHC proteins – MHC class I – ubiquitous – MHC class II – only on immune cells (APC)
Class I MHC on every?
nucleated cell
Class II MHC on?
B cell or other antigen-presenting cell (APC)
Preparation for an Adaptive Immune Response
• Antigen Processing
– Antigens processed for MHC proteins to display epitopes
– Different processes for endogenous and exogenous antigens
T Lymphocytes (T Cells) Produced in the?
red bone marrow and mature in the thymus
– Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches
– Antigen-binding sites are complementary to epitopes
– Have T cell receptors (TCRs) on their cytoplasmic membrane
T Lymphocytes Specificity of the T cell receptor (TCR)
– TCRs do not recognize epitopes directly
– TCRs only bind epitopes associated with a MHC protein
– TCRs act primarily against cells that harbor intracellular pathogens
T Lymphocytes, Types of T lymphocytes
– Based on surface glycoproteins and characteristic functions – Three types 1) Cytotoxic T lymphocyte – Directly kills other cells 2) Helper T lymphocyte – Helps regulate the activities of B cells and cytotoxic T cells 3) Regulatory T lymphocyte – Represses adaptive immune responses
Immune Response Cytokines
– Soluble regulatory proteins that act as intercellular signals
– Cytokines secreted by various leukocytes
– Cytokine network
– The complex web of signals among all the cells of the immune system
Immune System Cytokines
– Interleukins (ILs)
* Signal among leukocytes
– Interferons (IFNs)
* Antiviral proteins that may act as cytokines
– Growth factors
* Proteins that stimulate stem cells to divide
– Tumor necrosis factor (TNF)
* Secreted by macrophages and T cells to kill tumor cells
and regulate immune responses and inflammation
– Chemokines
* Chemotactic cytokines that signal leukocytes to move
Cell-Mediated Immune Responses Respond to?
intracellular pathogens and abnormal body cells
• The most common intracellular pathogens are viruses
• The response is also effective against cancer cells, intracellular protozoa, and intracellular bacteria
Activation of T Cell Clones and Their Functions
– Steps involved in activation of cytotoxic T cells – Antigen presentation – Helper T cell differentiation – Clonal expansion – Self-stimulation
Memory T Cells
– Some activated T cells become memory T cells
– Persist for months or years in lymphoid tissues
– Immediately functional upon subsequent contacts with epitope specific to its TCR
Cell mediated immunity: T Cell Regulation
• Damage + antigen are necessary for T cell activation.
– Regulation needed to prevent T cell response to autoantigens
– T cells require additional signals from an antigen-presenting cell
– Interaction of the T cell and antigenpresenting cell stimulates the T cell to respond to the antigen
Humoral immune responses mounted against?
exogenous pathogens • Activates only in response to specific pathogens • Two types – T-independent humoral immunity – T-dependent humoral immunity
Inducement of T-Dependent Humoral Immunity
– Plasma cells
– Majority of cells produced during B cell proliferate
– Only secrete antibody molecules complementary to the specific antigen
– Short-lived cells that die within a few days of activation
– Their antibodies and progeny can persist
Memory B Cells and the Establishment of Immunological Memory
– Produced by B cell proliferation but do not
secrete antibodies
– Have BCRs complementary to the antigenic determinant that triggered their production
– Long-lived cells that persist in the lymphoid tissue
– Initiate antibody production if antigen is encountered again
Specific immunity acquired during an individual’s life, Two types
– Naturally acquired
* Response against antigens encountered in daily life
– Artificially acquired
* Response to antigens introduced via a vaccine
Distinguished as either active or passive
– Active
– Passive
* Receive antibodies from another individual
Antigen binds to B cell receptor Poises B cell to respond
In many cases B cell needs?
conformation from helper T cells
- Ag enters the body and is phagocytized and processed by
macrophages
– These macrophages destroy Ag and present a portion on the surface of the macrophage next to self Ag
- Macrophages are called antigen-presenting cells (APC)
B Lymphocyte and Antibody Response Processed Ag combines with?
specific TH with the appropriate receptor
- APC releases substances to activate TH cell
- TH cell activates B cells to divide and differentiate
– Produce plasma cells and memory B cells
B Lymphocyte and Antibody Response Characteristic of primary response
Lag period of 10 to 12 days occurs before antibody detection in blood
- Activated B cells proliferate and differentiate into increasing numbers of plasma cells as long as antigen is present
– Net result is slow steady increase in antibody titer
Formation of memory
– B cells that have undergone class switching
- Produce IgG antibody
– IgG is antibody of memory
- IgG antibody can circulate in body for years allowing
protection against specific antigens
Characteristics of secondary response
– Memory cells responsible for swift effective reaction
of secondary response
- Often eliminate invaders before noticeable harm is done
Vaccine exploits phenomenon of immunologic memory
– Some memory B cells will differentiate into?
plasma cells
- Results in rapid production of antibodies
General characteristics of T cells
– Have multiple copies of T cell receptors
* Receptors have variable sites of antigen binding
– Role of T cells different from B cells
- T cells never produce antibodies
- T cells armed with effectors that interact directly with antigen
– T cell receptor does not react with free antigen
-Antigen must be present by APC
T Lymphocytes Antigen Recognition and Response
General Characteristics
– During antigen presentation, antigen cradled in grove
of major histocompatibility complex molecule (MHC molecule)
- Two types MHC
1) MHC class I
Bind endogenous antigen
2) MHC class II
Bind exogenous antigen
Two major function T cell populations
1) Cytotoxic T cells
– Proliferate and differentiate to destroy infected or cancerous “self” cells
– Have CD8 marker
– Recognize MHC class I
2) Helper T cells
– Multiply and develop into cells that activate B cells and
macrophages
– Stimulate other T cells; orchestrate immune response
– Have CD4 marker
– Recognize antigen display by MHC class II
Functions of Tc (CD8) cells
– Induce apoptosis in “self” cells
*Cells infected with virus or intracellular microbe
* Destroys cancerous “self” cells
– Nucleated cells degrade portion of proteins
* Load peptides into groove of MHC class I molecule
* MHC class I molecule recognized by circulating Tc cell
– Cell destroyed by lethal effector function of Tc cell
Tc cells releases pre-formed cytokines to destroy cell
Functions of TH (CD4) cells
– Orchestrate immune response
* Recognize antigen presented by MHC class II molecules
– MHC class II molecules found only on APC
* If TH cell recognizes antigen, cytokines are delivered
– Cytokines activate APC to destroy antigen
Role of TH cells in B cell activation
– If TH cell encounters B cell bearing peptide: MHC calls II complex
* TH cell responds by producing cytokines
– B cell is activated in response to cytokine stimulation
* B cell proliferates and undergoes class switching
* Also drives formation of B memory cells
Role of TH cells in macrophage activation
– Macrophages routinely engulf invading microbes
resistant to lysosomal killing
– TH cells recognize macrophage with engulfed microbes resistant to killing
– TH cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms
Natural killer cells descend from lymphoid stem cells
– They?
-lack antigen specificity
- No antigen receptors
- Recognize antigens by means of Fc portion of IgG antibodies
– Allow NK cells to attach to antibody-coated cells
- Actions augment adaptive immune response
– Important in process of antibody dependent cellular
toxicity
- Enable killing of host cells with foreign protein in membrane
- Natural killer cells recognize destroyed host cells with no
MHC class I surface molecules
– Important in viral infection
