Module 3 Flashcards
5 phases of adaptive immune response
- Antigen recognition
- Lymphocyte activation
- Eliminations of pathogens
- Contraction
- Memory
Antigen recognition
-after pathogen has entered body and and evaded innate immune defences, PAMPs are seen by antigen-presenting cells (APCs)
-APCs will present antigens to naive T-cells via their surface MHC proteins
Lymphocyte Activation
-requires a series of cellular interactions which lead to T-cell and B-cell differentiation and clonal expansion
Bcells -> plasmocytes
Tcells -> Cytotoxic T-cells
Eliminations of Pathogens
-depending on type of pathogen invading, most efficent defenses are unleashed: Hummoral or Cell-mediated
colonal Expansion
production of a large quantity of identical cells from the same original cell
Hummoral elimination of pathogens
plasmocytes produce antibodies that bind to extracellular pathogens
cell-mediated elimination of pathogens
cytotoxic t cells destory cells infected by intracellular pathogens or get activated by antigens presented by APCs
contraction (apoptosis of immune cells)
Once the pathogen is eliminated, the vast majority of activated lymphocytes undergo apoptosis and the immune response gradually declines
apoptosis
programmed cell death that occurs in a way controlled by the cell itself, which generate alsmost no damage to surrounding area
establishment of immunological memory
the few immune cells that survive the contraction phase differentiate into memory cells
When re-exposed to the same antigen, these memory cells proliferate quickly to generate an immune response much faster and more robust
which processes are induced in lymphocytes during their activation?
differentiation and clonal expansion
the role of MHC molecules
-helps identify and recognize self from non-self molecules to ensure IS does not attack the host
-display antigenic peptides on the surface of cells
-this can be recognized by TCR and co-receptors (CD4 or CD8) to initiate an adaptive imune response, which leads to elimination of foreign antigens
Classification of MHC molecules
MHC class I and MHC class II
MHC class I
CD8 cytotoxic cell
MHC class II
CD4 helper T cell
hoew do T cells recognize pathogens
cannot recognize extracellular pathogens by themselves they require an intermediate to present them
how do APCs internalize pathogens
phagocytosis OR receptor-mediated endocytosis and process them into peptides (antigens) and displayed on the MHC on the surface and are recognized by T cells
Receptor-mediated endocytosis
an endocytic process in which a cell absorbs external material by invagination of the plasma membrane. This process relies on receptors specific for the material being absorbed
two types of APCs
professional and nonprofessional
Professional APCs
MACROPHAGE, B CELL & DENDRITIC CELL
most efficent cells that both present antigens through MHC class II and express cosimulatory signals to activate helper T cells
nonprofessional APCs
other cell types can be inducedto express MHC class II complexes or stimulatory molecules, but normally they dont. This isbecause these cells will rarely be needed in this specific function and only for short periods of time in case of sustained inflammatory response
examples of nonprofessional APCs
fibroblasts and glial cells
the two pathways that lead to the formation of surface cell complexes
endogeneous and exogeneous
endogenous pathway
forms peptide MHC class I recognized by CD8 cytotoxic T cells
exogenous pathway
form peptide MHC class II recognized by CD4 helper t cells
Antigen processing by the endogenous pathway
-allows cell to proccess self or foreign intracellular particles and present them at the cell surface in order to be recognized by T cell receptors of cytotixic T cells
Why would cells need to present intracellular particles to the immune system
degrading self or foreign elements into peptide fragments which are transported to ER to associate with MHC class I. this complex is transported to golgi complex, further processed and transported to surface
5 main steps in the process of exogenous antigen presenting
- Antigen engulfment
- proteolytic processing
- Formation of MHC-antigen complex
- cell surface expression
- recognition by helper T cell
Exogenous: Antigen engulfment
antigen presenting cells engulf the foreign antigen by endocytosis forming and endosome. The antigen is generally recognized by PRRs
Exogenous: Proteolytic processing
Foreign antigens inside the endosome are broken down into fragments by proteolytic processing
what is proteolytic processing
protease cleaves one or more bonds in a target protein to modify its activity (activation, inhibition or destruction of activity)
Exogenous: formation of MHC-antigen complex
the vesicle containing the foreign fragments fuses with vesicles containing MHC molecules (originating from the endoplasmic retitculum via the golgi) forming MHC-antigen complexes
exogenous: cell surface expression
the MHC-antigen complex is transported to the plasma membrane, where it will be displayed on the surface of the cell
exogenous: recognition by helper T cell
the t cell receptor (TCR) on teh surface of a helper t cell binds to the MHC-antigen complex on the cell surface of the APC, which will initiate an adaptive immune response
B-cell Receptor (BCR)
the BCR is composed of a membrane-bound antibody and signal transduction molecules (ITAMs). BCRs recognize and bind to extracellular pathogens or toxins directly
ITAMs
an immunoreceptor tyrosine-based activation motif is composed of a repeated sequence of four amino acids in the cytoplasmic tails of cell surface proteins
T cell receptor (TCR)
-TCR complex is formed of a membrane bound antigen-specific molecule and signal transduction molecules
-TCRs in association with a co-receptor (CD4 or CD8) recognize and bind ti peptide MHC complex
CD4 co receptors are expressed on _________ cells, which recognie peptide MHC class ___________
Helper T cells, MHC class II
CD8 co receptors are expressed on _________ cells, which recognie peptide MHC class ___________
cytotoxic T cells, MHC class I
Lymphocyte Activation
involves many interactions with other immune cells, which will mediate the efficency of the specific immune response
cells involved in lymphocyte activation
macrophage, dendritic cell, b cell, helper t cell, cytotoxic t cell
cytokine networks
coordinate appropriate immune responses and modulate the balance between humoral and cell-mediated immunity
classes of cytokines depdndent on function and structure:
-chemokines
-interleukins
-interferons
-tumor necrosis factor
-growth factors
what does the immune system require to stimulate hummoral immunity and differentiation of B cells
CD4 helper T cells
two categories of antigens acle to activate B cells
thymus-dependent and thymus-independent
thymus-independent antigens
few antigens that can induce the production of antibodies by B-cells without the presence of a T-cell
T-cell dependent B cell activation
involves specific signals essential to the productionof functional plasmocytes and memory B-cells. This interaction induces an exchange of singals between 2 lymphocytes allowing activation of hummoral response
steps leading to signals in the process of B cell activation
- Peptide-MHC class II complex
- Signal 1: TCR- peptide:MHC complex
- expression of cosimulatory molecules
- Signal 2: Cosimulation
- Signal 3: Cytokines
- outcome of three signals
how many signals lead to b cell activation and what are they
- TCR-peptide:MHC complex Class II
- Cosimulation
- Cytokines
Step 1 of b cell activation
peptide-MHC class II complex
as the antigen binds BCR on a specific B cell does not produce a strong enough signal to activate the cell, the antigen is internalized by receptor-mediated endocytosis, processed and displayed on the cell membrane as MHC
At what stage does the B cell acting on APC express a high level of peptide: MHC complex on their cell surface
step 1
Step 2 b cell activation
Signal 1: TCR-peptide: MHC complex
the specific TCR complex and CD4 co-receptor on the T cell recognizes and binds to peptide: MHC complex on B cell
Step 3 b cell activation
expression of cosimulatory molecules
Signal 1 induces the expression of CD40L on the cell surface of the helper T-cell
Step 4 B cell activation
Signal 2: Co-stimulation
CD40L and CD28 expressed on the T-cell, respectively, bind to CD40 and B7 expressed on the V-cell inducing a costimulatory signal in both cells
The immune synapse structure
t-cells will not become properly activated if only signal molecules such a t-cell receptor and a peptide:MHC complex interaction. a immune synapse consisting of signal molecules AND adhesion proteins must be formed
what is an immune synapse
interaction between a t-cell and a APC
three components of an immune synapse
- Signal molecules (cSMAC)
- Adhesion molecules (pSMAC)
- signal regulation molecules (dSMAC)
signal molecules (cSMAC) in immune synapse
the central SMAC contians the molecules responsible for signalling between the two cells such as the TCR and peptie:MHC molecules
adhesion molecules (pSMAC) in immune synapse
the peripheral SMAC contains adhesion proteins, auch as integrins and cytoskeletal linker proteins, responsible for keeping the cells in contact long enough for signals to propogate
signal regulation molecules (dSMAC) in immune synapse
the distal SMAC consists of proteins with large extracellular domains that are responsible for helping regulate signal transduction
pattern of immune synapse
“bullseye” with three rings depicting three different cell clusters (SMAC). other immune synapses can be arranged differently
Function of Immune Synapse
Primary goal: effective activaton of the T cell
- holds signal proteins together to form stronger connections, giving enough time for right amount of signals
-reorganization structures inside the t cell, directing the release of cytokines close to target cell
-regulates lymphocyte activation
Chemokines
-induce chemotaxis
-call in cells to the region of infection
-play a key role in inflammation, cell mediated and hummoral responses and hematopoiesis
Interleukins
-contain over 10 subfamilies
-regulate immune and inflammatory responses
-primarily affect the proliferation and differentiation of various hematopoietic and immune cells
Interferons
-the most common and well-known interferon molecules are IFN-apla and IFN-y
-induce antiviral state - inhibit the replication process of virsus
- helps regulate immune responses
Tumor Necrosis Factor
-most common are TNF-alpha and TNF-beta
-involved in systemic inflammation (septic shock)
-involved in tumor regression
-can cause apoptosis (cell death)
Growth Factors
-stimulate: growth, proliferaition, healing, cellular differentiation
-regulate a variety of cellular processes such as immune responses
what is the outcome of B cell activation:
proliferation and differentiation into plasma and memory B cells
what is imunological memory
the ability of lymphocytes to respond more efficently to re-infection by a previously encountered antigen
when does immunological memory occur
when there is a second encounter with an antigen that induces a hightened state of immune reactivity, mediated by memory B cells
why do we get the flu multiple times if memory cells last for decades
due to different strains
memory B cells vs naive B cells
memory B cells differentiate from naive B cells and display the same membrane-bound antibody as parent cell
*memory b cells have longer
how do memory b cells work fast than naive b cells
naive b cells need to be activated through series of cell interactions (like antigen presentation) before they can differentiate into plasma cells and memory cells. memory cells can differentiate immediately into plasma cells making them faster
Natural Passive Immunity
-acquired by the fetus or newborn from the mother
-placental transfer of antibodies during pregnancy or breastfeeding
-short lived (6 months)
-no immunological memory for reciepent
Artificial passive immunity
-acquired by injection of serum containing antibodies
-immunity is temporary
-no immunological memory for reciepnt
Natural active immunity
-acquired through infection by a pathogen possibly leading to symptoms
-development of innate and adaptive immune responses
-immunological memory has significant change of being developed
Artificial Active Immunity
-acquired through vaccination
-development of innate and adaptive immune responses
-normally no symptoms
-imunological memory has significant chnage of edveloping
