Lecture 7 (Cut off for Exam 2) Flashcards
Third Line Defenses
Two Important Adaptive Immunity Characterisitcs
Pathogen specific and memory based.
Cellular Immunity
- Mediated by T-cells
- Target and kills cells infected and intracellular pathogen
Humoral Immunity
- Antibodies produced by B-cells
- Target extracellular pathogens
Immune Cell Development
Lymphoid Stem Cell»_space; Small Lymphocyte»_space; T-Cell / B-Cell (latter goes into plasma cells)
Cells Involved in Adaptive Immunity Activation (6)
- Macrophage and dendritic cells
- Collectors and informers
- Helper T-cells
- Cytotoxic T-Cells
- B-Cells
- Memory B & T-Cells
Collectors & Informers
- ingest and kill microbes
- antigen presenting and processing
- activation of adaptive immunity
Helper T-Cells
- Central Orchestrators of humoral and cellular immunity
- CD4 markers on surface
- Direct adaptive immunity
- Interact with APCs using MHCII
Cytotoxic T-Cells
- Assassins
- CD8 markers on surface
- Discriminately kill infect host cells (intracellular pathogens)
- Interact with infected cells using MHCI
B-Cells
- Antibody factories
- Humoral immunity
Memory Cells
- Provide long term immunity
- Programmed for faster and stronger reactions
Antigens
- Antibody Generator
- Activates specific adaptive immunity
- Different from PAMP (specificity)
- Also known as immunogens
Bacterial examples of Antigens
Capsule, fimbriae, flagella, LPS, cell wall, toxins
Viral Examples of Antigens
Capsid, spikes, envelopes
Epitopes
Smallest “recognizable” part of antigen that reacts with T-cells and antibodies. Each antigen has multiple epitopes on it.
Antigenicity Factors (3)
- Molecular class
- Shape
- Size
Molecular Class + Antigenicity
- Proteins = most antigenic
- Carbs = least antigenic
- Lipids/nucleic acids = not antigenic usually
Shapes + Antigenicity
- 3D shape = important
- Provides epitopes
Size + Antigenicity
- Larger molecules = more antigenic
- Haplens = too small to be antigenic on their own
Proteins + Antigenicity
Ex: fimbriae, flagella
- Cellular and humoral response
- Longest lasting immune response
- Programmed memory
Carbohydrates + Antigenicity
Ex: Capsule
- Only humoral response
- Weaker and shorter immune response
- Lacks programmed memory
Lymphocyte Receptors
-Surface molecules that bind antigen epitopes
-Provide specificity of immune response
Ex: B-Cell and T-Cell receptors
B-Cell Receptors
- Recognize many molecule types
- Soluble or pathogen-associated
- Doesn’t undergo phagocytosis, internalizes epitopes after they bind to B-cell receptors
T-Cell Receptors
- Recognize proteins only
- Require antigen presentation
Major Hisocompatibility Complex
- Aka MHC, examples = MHC I & MHC II
- Cell surface glycoprotein molecules
- On surface of all nucleated cells
MHC I
- All nucleated cells have it
- Presents normal, abnormal, and foreign antigens
- Presents to cytotoxic T-cells and NK cells
MHC II
- Macrophages, dendritic cells, & B-Cells has receptor
- Presents only abnormal or foreign antigens
- Presents to helper T-cells
Antigen Presenting Cells
- All nucleated cells present antigens with MHC-I
- Professional phagocytes = macrophages, dendritic cels
- APCs present with MHC II to activate helper T-Cells
T-Cell Production
- Produced from multi-potent stem cell
- Differentiate into lymphoblasts in red marrow
T-Cell Maturation
- Lymphoblasts enter blood stream
- Travel to thymus for maturation over 3 phases
- Immature in thymus = thymocytes
Phase I T-Cell Maturation
- Negative selection against thymocytes with defective T-cell receptor (TCR)
- Forces apoptosis to occur (programmed cell death)
Phase II T-Cell Maturation
- Positive selection for MHC interactions
- Thymocytes that interact with MHC appropriate receive positive signals to move though maturation stages
- Thymocytes that interact inappropriately are not stimulated and die through apoptosis
Phase III T-Cell Maturation
- Occurs in cortex and medulla
- Negative selection to remove self-reacting thymocytes through apoptosis
- Referred to central tolerance - minimizes T-Cells in peripheral blood and tissues that would cause autoimmunity
Peripheral Tolerance
Mechanisms to catch missed self-reacting T-cells
Results of Thymic Selection
- 2% of thymocytes allow to make and enter blood stream lymphatic system
- Travel to secondary lymphatic tissues (tonsils, spleen, lymph nodes) and await to by activated by APCs
Diversity of T-Cell Receptors
- need diversity of receptors to have different epitope recognizers
- need to recognize different parts or types of bacteria and viruses
- different regions of receptor have different coding possibilities to make up the receptor diversity
Types of T-Cells
- *1. Helper
2. Regulator - *3. Cytotoxic
- *Focus on these**
Regulatory T-Cell
Have CD4. Interact with APCs with MHCII. Act on peripheral tolerance.
Activation of Helper T-Cells
- Naive Helper T-Cells interact with APC which activate the helper cell
- CD4 on Helper T-Cell anchors the MHCII in place
- Proliferates and differentiates into TH1, TH2, and memory helper T-Cells
TH1 Functions
- Stimulate Cytotoxic T-Cells to kill more effectively
- Stimulates memory CTC production
- Stimulates macrophages and PMNs to kill more effectively
- Stimulates NK cells to kill more effectively
TH2 Functions
- Stimulate B cell differentiation into plasma and memory cells
- Direct antibody class switching in B cells
TH17 Function
Stimulate immunity to chronic mucocuntaneous candidiasis
Memory TH Functions
- Remember specific pathogens
- Programmed to respond faster and stronger to pathogens that are encountered again
Activation of Cytotoxic T Cells
- Naive cytotoxic T-Cells interact with MHCI on infected cells, CD8 anchors in the interaction
- Cycotoxic T-Cell is then activated and releases perforins and granzymes
- Release of these cytotoxins can a controlled destruction of the infected cell via apoptosis
Perforins
Create membrane pores in infected cells
Granzymes
Enzymes that enter the infected cell and induce apoptosis.
Do Cytotoxic T-Cells and NK Cells have the same mechanism of killing?
Yes.
Do Cytotoxic T-Cells and NK cells have the same role in protection?
No.
Superantigens
- Bacterial or viral proteins that stay locked onto T-Cells
- Create a non-specific bridge between TCR & MHCII
- Leads to uncontrolled, excessive activation of Helper T-Cells
Cytokine Storm
What occurs when superantigens bind to Helper T-cells. Causes high fever, circulatory collapse, lowered blood pressure, shock, and death.
Production/Maturation of B-Cells
- produced in bone marrow like T-Cells
- Also mature in bone marrow, unlike T-Cells
- Cell that pass selection travel to spleen for final maturation
Selection Process of B Cells
- Positive Selection - cells with functional receptor
- Negative selection - against self-reacting cells, causes them to undergo apoptosis, receptor editing, or induction of anergy.
T Cell Receptors V.S. B Cell Receptors
T-Cell
- Antigen presented by APC
- Protein Antigens
B-Cell
- Free antigen OR antigen on intact pathogen
- Can be carbohydrate, lipid, or protein
Antibody Functions (5)
- Complement activation
- Neutralization
- Agglutination
- Opsonization
- ADCC
Antibodies + Complement Activation
Activates protein cascade that leads to increased inflammation, opsonization, and cytosis
Antibodies + Neutralization
Antibodies bind to parts of the pathogen that causes it to lose its ability to bind, move, etc.
Antibodies + Agglutination
Causes pathogens or foreign cells to be grouped together and more easily undergo phagocytosis
Antibodies + Opsonization
Binding to pathogen can opsonize it for better binding to macrophage receptors to undergo phagocytosis.
Antibodies + ADCC
Aka Antibody-Dependent Cell-Mediated Cytotoxicity
Binds to pathogen to increase its binding to NK cells that will kill it with cytotoxins.
B-Cell Activation Types (2)
- T-Cell Dependent
2. T-Cell Independent
T-Cell Dependent Activation
- Protein antigens
- Requires presentation of epitope to Helper T-Cell or B-Cell
- Diversity of antibody classes
- Strongest, longest, and memory immunity
T-Cell Independent Activation
- Carbohydrate, lipid, etc antigens
- No T-Cell Involvement
- Almost exclusively produced IgM antibodies
- Weaker, shorter, and no memory immunity
T-Cell Dependent Activation Process
B-Cell interacts with T-cell to release cytokines and then undergoes clonal expansion into memory and plasma cells. The latter makes antibodies, most commonly IgG
T-Cell Independent Activation Process
B-Cell interacts with pathogen cell on its own and is activated. Then releases mostly IgM antibodies.
Antibody Class Switching
- Directed by TH2 cells (T-Cell Dependent)
- Cytokines tell activated B-Cells to switch antibody classes based on needs
- Only changes the CONSTANT region, the antibody specificity/affinity is untouched
Mechanisms of Acquiring Immunity (4)
- Passive Natural - antibodies through breast milk or placenta
- Passive Artificial - Antibodies given through IV or injection that are harvested from humans or other animals
- Active Natural - gained through illness and recovery
- Active Artificial - gained via vaccines
Live, Attenuated Vaccines Advantages
- Multiply within host, more natural exposure
- Stimulates both cellular and humoral immunity
- May be life-long immunity from memory
- Use smaller doses with no boosters
- Spreads to others for “herd” immunity
Live, Attenuated Vaccines Disadvantages
- Preparations may be unstable, hard to store, hard to transport
- Risk of serious infections in immuno-compromised individuals
- Risks a reversion to virulent form
Inactived Vaccines Advantages
- Stable over longer period of time
- Easier to transport
- No active disease in immuno-compromised
- Can’t revert to virulent form
Inactivated Vaccines Disadvantages
- Larger and multiple doses
- Increases risks of side effects
- ONLY humoral defense, no cellular
Acellular/Subunit Vaccines
- Purified key antigens from pathogens
- Acellular = bacterial
- Subunit = viral
Acellular/Subunit Advantages and Disadvantages
Advantages
-Side effects are less likely
Disadvantages
- Activation of adaptive immunity may be weaker
- Immunity may be shorter
Toxoid Vaccines Definition/Advantages/Disadvantages
Inactivated bacterial toxins
Advantages
- Side effects are less likely
- Humoral immunity used to neutralize toxins
Disadvantages
- Doesn’t prevent bacterial infection
- Similar for subunit vaccines
Conjugate Vaccines Definition/Advantages/Disadvantages
Capsule polysaccharide conjugated to proteins
Advantages
- T-Cell dependent response to carbohydrate
- Immune response in young children achieved
Disadvantages
- Costly to produce
- No Protection against antigenic variation
DNA Vaccines
- Cells take up naked DNA
- Display foreign antigens with MHCI
- Secrete antigens
- Well rounded response
Vector Vaccines
- Attenuated virus introduces genes
- Attenuated bacteria express genes for virulence
