Week 7 material Flashcards
what makes up the immune system
Innate Immunity + Adaptive Immunity
where do immune cells come from
they derive from hematopoietic stem cells in the bone marrow
these stem cells differentiates into different types of blood cells - Hematopoiesis
what are the two types of stem cells hematopoietic stem cells differentiate into
myeloid stem cells + lymphoid stem cells
what cells are primarily innate - part of the innate response
- mast cell
- myeloblast
- natural killer cell
- basophil
- neutrophil
- eosinophil
- monocyte
what cells are primarily adaptive - part of the adaptive response
- small lymphocyte
- t lymphocyte
- b lymphocyte
- plasma cell
which cells are antigen presenting (occurs when innate response is presenting antigen to adaptive response)
- macrophage
- dendritic cell
what are the 2 types of lymphatic organs
Primary
- site where leukocytes develop
- red bone marrow = B cells
- thymus gland = T cells
Secondary
- site where the the effector cells get activated
- lymph nodes
- spleen
- appendix
what is innate immunity and adaptive immunity
what is innate immunity and adaptive immunity
Innate Immunity
- targets pathogens non-specifically
- responds quickly (0-4 hours)
- recognizes antigens by non-specific effectors
- removes antigen
- presents the antigen to the adaptive immune response + triggers it
Adaptive Immunity
- it attacks antigens specifically
- takes a longer time to attack
- recognizes the microbial-associated molecular patterns
Early Response (4-96 hours):
- inflammation occurs due to recruiting and activating effector cells to the site of infection
- removes antigen
Adaptive Immune Response (more than 96 hours):
- transports antigen to lymphoid organs
- naive B + T cells recognizes antigen
- clonal expansion + differentiation to effector cells
- removes antigen
characteristics of the immune system
- it’s fluid and systemic
- lymph flows everywhere and is interconnected to blood
-
naive lymphocytes circulate in the blood throughout the body
naive lymphocytes = B cells + T cells - antigen presenting cells gather samples of the antigen in tissues
- cells then go to the draining lymph nodes and communication here between the APC + lymphocytes allow for activation to occur
- naive lymphocytes enter lymph nodes from blood
- antigens from the site of infection are transported to the lymph nodes via lymphatics
- lymphocytes + lymph return to blood via the thoracic duct
what are the characteristics and key cell types of the innate immune response
Characteristics:
- not antigen specific
- does a general attack
- always ready to be initiated quickly (has pre-made cells ready to target pathogen)
- has no memory (doesn’t have the B cells to remember the pathogen incase it infects a 2nd time)
Key Cell Types:
- dendritic cells
- macrophages
- neutrophils
- NK cells
The events in innate response trigger the adaptive response
what are the 1st line innate defenses
Mechanical Barriers:
- skin
- tight junctions b/w epithelial cells
- cilia moving fluid
Chemicals:
- fatty acids on skin
- low pH in gut
- enzymes (lysozyme in saliva)
- antibacterial peptides/proteins
Microbiological Protection:
- symbiotic flora (biological organisms have a beneficial relationship with each other)
What is the innate response after the 1st line of defence is not able to prevent the pathogen
Chemical Defenses:
- Cytokines + Inflammatory Mediators (Histamine and Bradykinin) are released to recruit immune cells to the site of injury/infection
- Cytokines are proteins that allow for cells to communicate
Complement Activation:
- Circulating proteins can get activated to attack pathogens
Cellular Defenses:
- Neutrophils, Macrophages, + Natural Killer cells attack the pathogen via Phagocytosis
What is the Complement Cascade
The activation of a cascade of proteins
- includes a group of Plasma Protein Mediators
- bacteria activates more than 30 protein mediators
- there are precursors that circulate in the body and become functional when involved in Complement Activation
- Complement Activation works in 4 ways:
1. Opsonization
2. Inflammation
3. Chemotaxis
4. Cytolysis
- there are 4 proteins (C6, 7, 8, 9) that come together to form a Membrane Attack Complex
- the complex creates pores in the Gram-Negative Bacteria’s outer membranes
how do Leukocytes move/where do they go
- Cytokines + Complement get released and attract leukocytes to the site of infection
- chemical attractants released by pathogens
- chemical signals released by nearby injured cells
- leukocytes roll along the blood vessels
- Extravasation occurs = leukocytes squeeze through the walls of the capillary blood vessels to get to the infected tissue
What are the steps of Phagocytosis
- Chemotaxis = the directed migration of a cell in response to a chemical signal and chemical attractant
- Phagocytes go through chemotaxis to get to microbes
- Microbes adhere to the chemotaxis
- chemotaxis create false feet to encapsulate the microbe - Microbes get ingested by phagocytes
- Fusion of a series of vesicles (one of them being lysosomes)
- phagosome + lysosome merge together to make a phagolysosome - microbes get killed by enzymes and other chemicals
- elimination/exocytosis
- degraded proteins can either go through exocytosis OR are important and will be presented elsewhere
how do phagocytes recognize pathogens
they recognize the **Pathogen-Associated Molecular Patterns (PAMPs)
- these are molecular structures that are common to many groups of pathogenic microbes
Examples of PAMPs
- Peptidoglycan
- Flagellin (part of bacterial flagella)
- Lipopolysaccharide (LPS) from outer membrane of gram negative bacteria
what does the complement system involve?
serum proteins involved in nonspecific defense
what are antigens
means antibody + generator
- a molecule from the body that gets recognized as foreign and worth attacking
- it triggers an immune response which results in the body creating antibodies
- they’re unique to the pathogen they’re a part of/all microbes have different antigens
- important for adaptive immunity that they have a specific response
- can be a part of bacteria, viruses, fungi, and protozoa
- ex: capsules, flagella, cell walls, toxins, envelopes, and spike proteins
- can belong to many molecular classes, carbohydrates, lipids, nucleic acids, + proteins
which antigen works best of which has the highest antigenic potential
proteins due to their specific 3D structure
what are epitopes
- smaller exposed regions on the surface of antigen
- 1 antigen can have many epitopes
- antibodies bind to a single epitope
what are the different types of antigens
exogenous - on the surface of microbes
endogenous = when the virus infects a host cell and causes it to have surface antigens
autoantigens - an uninfected cell has antigens on its surface
what makes up a well functioning immune system
it’s able to tell the difference between a molecule that comes from the body and a molecule that doesn’t belong to or in the body
what is the general sequence of immunity
INNATE
1. inflammatory response
2. antigen presenting cells brings the antigen to the lymph nodes
ADAPTIVE
3. Helper CD4+ T cells are activated by antigen presenting cells
4. B cells + Cytotoxic CD8+ T-cells are activated
B cells activated
- plasma cells create antibodies
- some become memory cells
- depends on TH2
Cytotoxic CD8+ T cells
- effector cells actively kill infected cells
- some become memory cells
- depends on TH1
How do antigen presenting cells present the antigen to T-cells
- dendritic cells + macrophages go from the periphery -> lymph nodes
- naive T-cells get activated to become effector cells
- T-cells only recognize the protein fragments that come from antigens so the antigens have to be processed
what are examples of antigen presenting cells
- dendritic cells
- macrophages
- B cells
how do T-cells receptors recognize antigens
MHC bind to peptide fragments of the antigen and presents them on the cell surface
There are 2 types of MHC
MHC I = activates cytotoxic T-cells
MHC II = activates helper T cells
How does dendritic cells present antigens
- The antigen is engulfed via phagocytosis by the dendritic cell. The antigen is now in a phagosome
- Lysosome fuses w/ phagosome and digests the antigen
- Immunodominant epitopes are presented on the cell surface via MHC II
The dendritic cells with the epitope/antigen go to the lymph nodes and interact w/ the lymphocytes that enter via the blood
- Immature dendritic cells live in the peripheral tissues
- Dendritic cells go to the lymph nodes via afferent lymphatics (via the lymphatic vessels)
- Mature dendritic cells are now in the deep cortex
What are other names for the B cell response and the T cell response
B cell response = Humoral Immunity
T cell response = Cell-mediated Immunity
How do helper T cells/CD4+ get activated
Activation requires 3 signals
Signal 1 = T cell receptor recognizes the peptide-MHC
Signal 2 = APC have co-stimulatory molecules. These molecules interact with the ligands on T cells
Signal 3 = Cytokines - these differentiate T cells into different types of effector T cells
What are the 2 types of CD4+ T cells
Th1T cell
- Regulates macrophages and cytotoxic T cells via cell-cell interactions + secreting TH1 cytokines
- Macrophages and Cytotoxic T cells are part of the adaptive inflammatory response
Th2 T cell
- Regulates B cells and the class of antibody they create to regulate the antibody response
- They regulate B cells and their antibody production via cell-cell interaction ad secreting Th2 cytokines
Some of general T cells can turn into memory T cells
What are the characteristics and key cells involved in adaptive immune response
Characteristics
- antigen specific
- forms memory
- a longer process to activate or trigger
*Key Cells**
- B cells
- T cells - Th1 + Th2 (CD4+) and cytotoxic (CD8+)
What do B cells and T cells use to recognize epitopes
Both cells use receptors that are antigen specific (only binds to 1 epitope). The binding of the epitope to these receptors is one of the signals that activates the B cells and T cells.
- B cells use B cell receptors
- These are antibodies bound to the B cell’s membrane
- T cells use T cell receptors
- These recognize epitopes when MHC presents them
Why are BCR and TCR antigen specific
Due to receptor diversity
- There are a lot of different receptors with different antigen-binding sites
To create this diversity of receptors: different combinations of gene fragments get pasted together and create a functioning antibody and TCR gene
What is the clonal selection theory
Explains how the immune response can be triggered by a large variety of antigens + the cell’s memory
How do lymphocytes develop
-
Pre-T lymphocytes and Pre-B lymphocytes develop in the bone marrow
( these are immature lymphocytes) - 1 cell can develop a large number of lymphocytes with different specificity
- T cells move to thymus
- B cells move to bone marrow
- the mature into naive lymphocytes (ready to attack but haven’t been activated yet)
- Mature naive cells are activated into effector cells in the secondary lymphatic tissue (lymph nodes, spleen)
What is clonal selection and clonal expansion
Both of these are part of a process where specific immune cells (T cells and B cells) get chosen and replicated to respond to a pathogen
Clonal Selection
- Immune cells (T cells or B cells) that match with the antigen gets chosen
Clonal Expansion
- The selected immune cells rapidly multiply and make a large army to fight the pathogen
Steps of the humoral immunity/ B cells activation
- Antigen presented to the T cell activates it
- T cell differentiates into Th2 cell
- Clonal Selection - a complementary B cell clone gets chosen
- Th2 cell activates the B cell clone (B cells have MHC II on their surface)
Activation follows Clonal Selection and Expansion
COMPLETE ACTIVATION
- Needs 3 signals
Signal 1: BCR recognizes the antigen
Signal 2: APC have co-stimulatory molecules. These molecules interact with the ligands on T cells
Signal 3: Cytokines - differentiate the B cells into antibody secreting cells(Plasma cells and Memory B cells)
- B cells differentiate into plasma cells + memory B cells/B cell activation and Clonal expansion occurs
- B cell gets activated and then will go through expansion of the 2 differentiated cells
What are plasma cells and memory cells
Plasma Cells = produces antibodies and secretes large amounts of them
Memory Cells = circulates and gets reactivated when it gets exposed to the antigen
- helps to make the secondary immune response be stronger and faster
What are the structure and functions of antibodies
AKA immunoglobulins or gamma globulins
- Y shaped proteins
- Antigen binding sites = variable regions at the ends of the 2 arms
- Binds to antigens (microbes, cells, molecules, anything that triggers the production of antibodies)
- Binds to antigens via non-covalent bonds
What are the classes of antibodies
IgM = the first antibody that gets created
IgG = most common and long-lasting
IgA = associated to body secretions
IgE = involved in the response to parasitic infection + allergies
IgD = function unknown
What are the 5 functions of antibodies
- neutralization
- opsonization
- oxidation
- agglutination
- antibody-dependent cellular cytotoxicity (ADCC)
How do cytotoxic T cells/CD8+ get activated
- The TCR bind to the MHC-viral peptide complexes - this tells the CD8+ T cell to kill the infected cell with perforins and granzymes
- Activated APC have co-stimulatory molecules on its surface which helps to activate the CD8+ cells
- APC present antigens to the T helper cell to activate it
- T helper cell differentiates into Th1 cell
- Cytotoxic T cells are activated by APCs and are differentiated with the help of Th1
COMPLETE ACTIVATION
- Needs 3 signals
Signal 1: TCR recognizes the antigen presented by MHC I
Signal 2: APC have co-stimulatory molecules. These molecules interact with the ligands on CD8+ T cells
Signal 3: Cytokines - differentiates the T cells
- Was created by Th1 cells
- Clonal expansion and differentiation into memory T cells and active Tc cells
How do proteins that come from a virus end up on the MHC I
- Proteins that come from a virus gets created inside of the cell, specifically in the cytosol
- These proteins bind to the MHC I in the ER and then the MHC I with the bound proteins gets transported out on to the cell surface
How do pathogens avoid immune responses
- Using a polysaccharide capsule
- Hiding in the macrophage
- Antigenic drift
- Superantigen production
What does a polysaccharide capsule do
- Prevents phagocytosis done by innate immune cells from occurring
- Makes it difficult for APCs to present antigens
- Prevents complement proteins from doing opsonization
- Makes it harder for antibodies to bind
What happens when TB hides within a macrophage
- Prevents phagosome-lysosome fusion - macrophages can NOT digest TB
- Macrophage with the TB hiding in it carries it into the bloodstream
- Macrophage squeezes through blood-brain barrier allowing for TB to reach the CNS
What is antigenic drift
- The host cell develops an immune response to the virus that infected it by creating antibodies that can bind to the virus’s antigens
- Small mutations to the surface proteins/antigens of the virus can turn the virus into another virus
- This makes it unrecognizable to the host cell’s antibodies which allows it to infect the host cell
What is superantigenic production
Superantigens = exotoxins created by a specific bacteria
- Superantigens avoid the path the antigens take to activate the T cell by binding the TCR to the MHC without any specific antigen bound to it
- Causes for a large amount of T cells to be activated and uncontrollably release cytokines
