CH 15 - Adaptive Immune Response Flashcards
Adaptive immunity
Protection provided by immune responses that improve due to exposure to antigens
Involves B & T cells
Antibody
Y-shaped protein that binds antigen
Antigen
Molecule that reacts specifically with either antibody or antigen receptor on lymphocyte
Antigen-presenting cells (APCs)
Cells that can present exogenous antigens to T cells
Ex: dendritic cells, B cells, macrophages
B cell
Type of lymphocyte programmed to make antibody molecules
Cell-mediated immunity (CMI)
Immunity involving T-cell response
Clonal selection
Process in which lymphocyte’s antigen receptor binds to antigen, allowing lymphocyte to multiply
Cytotoxic T cell
Type of lymphocyte programmed to destroy infected or cancerous “self” cells
Dendritic cell
Cell type responsible for activating naive T cells
Effector lymphocyte
Differentiated descendant of an activated lymphocyte
Its actions help eliminate antigen
Helper T cell
Type of lymphocyte programmed to activate B cells & macrophages & assist other parts of adaptive immune response
Humoral immunity
Immunity involving B cells & antibody response
Lymphocytes
Group of WBCs (leukocytes) involved in adaptive immunity
Ex: B & T cells
Major histocompatibility complex (MHC) molecules
Host cell surface proteins that present antigens to T cell
Plasma cell
Effector form of B cell
Functions as antibody-secreting factory
Tc Cell
Effector form of cytotoxic T cell
Induces apoptosis in infected/cancerous “self” cells
Th Cell
Effector form of helper T cell
Activates B cells & macrophages & releases cytokines that stimulate other cells of the immune system
Primary vs. Secondary Response
Primary Response
(Responding B cell , lag period, peak response, effect)
1st response to a particular antigen
- Naive B cells
May take week or more to develop
- Lag period of 10-12 days
(before Ab detection in blood)
- Peak response = 7-10 days
Activated B cells proliferate & differentiate into increasing #s of plasma cells in presence of Ag
- Slow/steady increase in Ab titer
Overtime, some B cells undergo changes enhancing immune response
Thymus-dependent & independent Ags
Secondary Response
Immune system remembers pathogen on subsequent exposure
- Memory B cells
Enhanced & specific immune response
- Often limit invaders before noticeable harm done
- Lag period of 1-3 days
- Peak response = 3-5 days
- 100-1000x greater response than primary
- Higher Ab affinity
Vaccines exploit immunologic memory
Some memory B cells differentiate into plasma cells
- Rapid production of Abs
Thymus-dependent Ags
Basis of Vaccine
Adaptive immunity
Ex: Milkmaids in the 1700s resistant to smallpox because exposed to cow pox 1st (related)
Adaptive Immunity Divided Into:
- Humoral immunity
- Ab mediated (B cells)
- Eliminates EXTRACELLULAR pathogens - Cellular immunity
- T cell mediated
- Eliminates INTRACELLULAR pathogens
Humoral Immunity:
Receptors/Cell Types
Mediated by B cells
(develop in bone marrow)
- B cell receptors (BCRs)
- Membrane-bound derivative of - Plasma cells
- Produce Abs when Ags bind BCRs - Memory cells
Cellular Immunity:
Receptors/Cells Types
Mediated by T cells
(mature in thymus)
- T cell receptors (TCR)
- Help with Ag recognition - Cytotoxic (CD8+) T cells
- Helper (CD4+) T cells
Lymphoid System
Collection of tissues/organs through which lymph travels
Includes:
1. Lymphatic vessels
2. Primary lymphoid organs
3. Secondary lymphoid organs
Major Functions of Lymphoid System
- Concentrate Ags into lymphoid organs
- Circulate lymphocytes through lymphoid organs (so can interact with Ags)
- Carry products of immune response to bloodstream/tissues (Abs & effector cells)
Lymph
Extracellular fluid that bathes tissue (result of circulatory system)
Lymphatic vessels carry to body tissue
- Travels through vessels to lymph nodes
Contains:
1. Tissue products
2. Ags
3. Abs
4. Cells (lymphocytes)
Areas where immune cells congregate at mucosa to defend against penetrating microbes:
MALT = mucosa-associated lymphoid tissue
SALT = skin-associated lymphoid tissue
GALT = gut-associated lymphoid tissue
BALT = bronchus-associated lymphoid tissue
Primary Lymphoid Organs
Bone marrow & thymus
Location where stem cells destined to become B & T cells mature
Secondary Lymphoid Organs
Sites where mature lymphocytes gather to encounter Ags
Includes:
1. Lymph nodes (trap Ags)
2. Spleen (trap foreign substances)
3. Tonsils
4. Adenoids
5. Appendix
Antigens
Compounds that elicit Ab production
- “Ab generator”
- Any compound that reacts with Ab or antigen receptor on lymphocyte
Immunogens elicit immune response
- Proteins & polysaccharides = strong responses
May NOT elicit immune response
- Substances with MW < 10,000 da
- Lipids & nucleic acids
Antigenic determinate (epitope)
Determines recognition of Ag
B & T cells recognize distinct epitopes
Structure of Antibodies
Monomer = basic unit (IgG)
Made up of 4 chains of amino acids held together by disulfide bonds
- 2 chains = heavy
- 2 chains = light
Constant region (each heavy & light chain)
- Fc region binds Fc receptors
Variable region (each heavy & light chain)
- Unique to each Ab
- Antigen-binding site
- “Fab” region
Protective Outcomes of Ab-Ag Binding
- Neutralization
- Prevents toxin/virus from interacting with/entering cell - Immobilization & prevention of adherence
- Ab binds to cellular structures to interfere with function (ex: flagellum) - Agglutination & precipitation
- Clumping of bacterial cells by specific Ab (involves 2 binding sites)
- Makes phagocytosis easier - Opsonization
- Ab coats bacteria to enhance phagocytosis - Complement activation
- Ab binding surface of microbe triggers classical pathway - Antibody-dependent cell-mediated toxicity (ADCC)
- Fc region of multiple Abs binds cell (makes target)
- Substances secrete by nonspecific cytotoxic cells
5 Classes of Abs:
- IgM
- IgG
- IgA
- IgD
- IgE
IgM
1st to respond to infection (produced 1st by B cells)
5-13% of Abs in circulation
Pentamer
- 5 monomer units joined together at constant region
- 10 binding sites (good for aggregates)
Monomer on surface of B cells
Functions of IgM
- Elicits classical complement cascade
(most efficient) - Agglutination & precipitation reactions
- Produced during immune responses to T-independent antigens
- Can be formed in fetus if infected in utero
IgG
Dominant Ab in circulation (80-85%)
Monomer
Functions of IgG
- ONLY Ab that can cross placenta
- Present in colostrum (protects babies after birth - absorbed by intestinal tract)
- Ab of memory
- Induces classical complement cascade
IgA
10-13%
- Secreted form (sIgA) = majority
Monomer in serum
Dimer in secretions
- Monomer connected by J chain
- Ferried across epithelia by poly Ig receptor
- Secretory component protects Ab from proteolytic enzymes
Found in:
1. Breast milk
2. Mucus
3. Tears
4. Saliva
Functions of IgA
- Mucosal immunity
- Protects babies from intestinal pathogens
IgD
<1%
Monomer
Function of IgD
Development & maturation of Ab response
IgE
Barely detectable in circulation (<0.01%)
- Bound by FcRs of mast cells & basophils
Monomer
Functions of IgE
- Detect parasites/Ags & release granule contents (bound IgE)
- Allergic reactions (anaphylaxis)
Clonal Selection Theory
Clonal selection
- Antigen binds to only 1 preformed lymphocyte
- Initiates multiplication of Ag-specific lymphocyte
Clonal expansion
- Repeated cycles of cell division generates population of copied Abs
Without sustained stimulation, cells undergo apoptosis
- Curtails immune response
Lymphocyte Characteristics
- Immature
- Naive
- Activated
- Effectors
- Memory lymphocytes
Immature Lymphocytes
NOT fully developed Ag-specific receptor
Naive Lymphocytes
Most B cells
Have Ag receptor
Have NOT encountered Ag
Activated Lymphocytes
Bound Ag
Able to proliferate
Effector Lymphocytes
Descendants of activated lymphocytes
- Activation/differentiation pushed by T cells
Produce specific cytokines
Include:
1. Plasma cells
2. T helper cells
3. Cytotoxic T cells
Memory Lymphocytes
Long-lived descendants of activated lymphocytes
Remembers Ag on subsequent exposure
Responsible for speed/effectiveness of secondary response
Continue producing Abs forever (permanent)
B Lymphocytes & Ab Response
(steps of B cell activation)
- Ag binds BCR
- Ag internalized by B cell & degraded
- Peptide fragments loaded into MHC II
- Peptides presented to T cells (APCs) - B cell needs confirmation from T helper cells
- Costimulatory or 2nd signal - Th cell recognizes Ag:
- Releases cytokines that activates B cells (differentiate/divide)
- Produce plasma cells & memory B cells - Th cell does NOT recognize Ag:
- Immune response may become “tolerant” to Ag
- No Abs produced
(even though BCRs engaged)
Changes to Proliferating B Cells in Primary Response
- Affinity maturation
- Class switching
- Formation of memory cells
Affinity Maturation
B cells that bind Ag most tightly & for longest duration most likely to proliferate
- Others undergo apoptosis
Fine tunes quality of response (specificity)
Form of natural selection
Class Switching
B cells initially programmed to differentiate into plasma cells
- Secrete IgM
Helper T cells produce cytokines that influence proliferation/differentiation
- Some B cells switch programming
- Secrete other classes of Abs
Proliferation Cytokines
IL-2
IL-4
IL-5
Differentiation Cytokines
IL-2
IL-4
IL-5
IFN-gamma
TNF-beta
Antibody Diversity
Not enough DNA for separate genes to encode each Ab
- Gene rearrangement
- Maturing B cells selects 3 segments & combines together (VDJ)
- V = 65
- D = 27
- J = 6 - Imprecise joining
- Nucleotides added/deleted - Combinatorial associations
- Specific groupings of light & heavy chains
Formation of Memory
Involves B cells that have undergone class switching
- Produce IgG (Ab of memory)
Circulate in body for years/lifetime
- Protect against specific Ags
Memory lymphocytes responsible for speed/effectiveness of 2ndary response
T-dependent Ags
Compounds that evoke immune response ONLY with aid of T helper cells
Protein Ags
T-independent Ags
Activate B cells WITHOUT helper T cells
Carbohydrates (polysaccharides) & lipids (LPS)
- Capsules = poor T-dependent response
BCRs bind Ag simultaneously for B cell activation (multiple engagement)
Immune systems of young children (~2 yr) respond poorly to T-independent Ags
T Cell Receptors (TCRs)
T cells have multiple copies of TCRs
Receptors have variable sites of Ag binding (similar to Abs - recombination)
Role of T cells
NEVER produce Abs
- Do NOT react with free Ag
Armed with effectors that interact directly with target cells
- Ag MUST be presented by APC
Peptide-binding groove
Ag cradled in groove of major histocompatability complex molecule (MHC) during Ag presentation
2 Types of MHC
- MHC class I
- Binds endogenous Ag (inside cell)
- Engagement with CD8 cells
- Found on ALL body cells
- “Kill me” signal - MHC class II
- Binds exogenous Ag (outside cell)
- Engagement with CD4
- ONLY found on APCs
- Drives Ab response
T Lymphocytes - Ag Recognition & Response
- Naive T cells recognize Ag presented by dendritic cell
- Recognizes Ag presented & dendritic cell expresses co-stimulatory molecule
- Activated
- Proliferate & develop effector function - Recognizes Ag presented & dendritic cell NOT displaying co-stimulatory molecule
- Driven to apoptosis OR becomes unresponsive to Ags
Endogenous Pathway
- Endogenous Ag degraded by protease
- Peptide transported to rough ER via TAP (transporter)
- Class I MHC captures peptide & chaperons dissociate
- Class I MHC-peptide transported from rough ER to Golgi complex to plasma membrane
Exogenous Pathway
- Class II MHC alpha & beta bind invariant chain
- Blocking binding of endogenous Ag - MHC complex routed through Golgi to endocytic pathway compartments
- Invariant chain degraded
- Leaving CLIP fragment - Exogenous Ag taken up, degraded, & routed to endocytic pathway compartments
- HLA-DM mediates exchange of CLIP for Ag peptide
- Class II MHC-peptide transported to plasma membrane
Antigen Presenting Cells (APCs)
- Dendritic cells
- Macrophages
- B lymphocytes
Dendritic Cells:
APC Function
Ag uptake:
- Endocytosis
- Phagocytosis (Langerhans cells)
Activate:
1. Naive T cells
2. Effector T cells
3. Memory T cells
Macrophages:
APC Function
Ag uptake:
- Phagocytosis
Activated macrophages activate:
1. Effector T cells
2. Memory T cells
B lymphocytes:
APC Function
Ag uptake:
- Receptor-mediated endocytosis
Resting B cells activate:
1. Effector T cells
2. Memory T cells
Activated B cells activate:
1. Naive T cells
2. Effector T cells
3. Memory T cells
2 Major Functional T Cell Populations
- Cytotoxic T cells (Tc)
- Helper T cells (Th)
Cytotoxic T cells (Tc)
Proliferate & differentiate to destroy infected or cancerous “self” cells & in graft rejection
CD8 marker
Recognize MHC class I
Helper T cells
Orchestrate immune response
- Multiply/develop into Th1-type & Th2-type
- Stimulate other T cells
Th1-type
- Activates cell-mediated immune responses & macrophages
Th2-type
- Activates humoral responses
CD4 marker
Recognize MHC class II
Functions of Tc (CD8) Cells
- Induce apoptosis
- Self cells infected with virus/intracellular microbe
- Cancerous self cells
- Foreign cells involved with graft rejection - Secretes cytokines
Tc (CD8) Cells:
Mechanism of Action
Recognize MHC class I molecule loaded with peptide on nucleated target cell
Release pre-formed cytotoxin that induce lysis or apoptosis (perforin, proteases, granzymes)
Induces apoptosis through binding of Fas ligand (FasL) on activated CD8 T cell to Fas on target cell (engaging apoptotic receptor)
Functions of Th (CD4) Cells
- Orchestrate immune response
- Role in cell activation
- Role in macrophage activation
- Recognize macrophage with engulfed microbes resistant to killing
- Deliver cytokines that activate macrophages & induce more potent destructive mechanisms
- Macrophages fuse to form giant cell (granuloma) when cannot deal with microbial infection (prevents dissemination)
Th (CD4) Cells:
Mechanism of Action (in B cell activation)
- Recognize MHC class II
- Deliver cytokines
- B cell activated in response to cytokine stimulation (proliferation, class switching, formation of memory B cells)
Negative Selection:
“Self” Reactive B cells
Aka: clonal deletion
Process of eliminating B cells that bind “self” antigens
- Undergo apoptosis
Naive B cells that recognize Ag in secondary lymphoid tissue eliminated if do not receive 2nd signal from T helper cell
Failure leads to production of autoAbs (autoimmune disease)
Selection of T cells
Negative selection
- “Self” reactive T cells
- Recognize/bind “self” Ags
- Undergo apoptosis
Positive selection
- ONLY T cells that recognize/bind MHC
- TCR recognizes peptide:MHC complex
Natural Killer (NK) Cells
Descend from lymphoid stem cells
Mediate lysis of host cells altered by:
1. Stress
2. Viral infection
3. Transformed into tumor cells (express less MHC I)
Expression of relatively high levels of MHC I on normal cells protects against NK-mediated killing
- Virus/pathogens that down-regulate MHC I targeted
Regulated by balance of positive signals (activating receptors) & negative signals (inhibitory receptors)
Involved in innate immunity
- Antibacterial
- Lipid Ags specific to tumor cells
A group of interacting serum proteins that provide nonspecific defense mechanism is:
Complement
NOT:
- Interferon
- Glycoprotein
- Lysozyme
