Principles of Adaptive Immunity Flashcards
Innate Immunity
Focus defense mechanisms onto the site of infection
- Non specific
- Non adaptive (no memory)
Adaptive Immunity
Focus defense mechanisms onto the pathogen itself
Specificity
Lymphocytes express antigen receptors that recognize specific features (antigens) of a microorganism = adaptive immune system can distinguish between different microorganisms
Immune Memory
Second encounter with the same pathogen will induce a more rapid and efficient adaptive immune response
Naive Lymphocytes
Have been exported from primary lymphoid tissues into blood and secondary lymphoid tissues
- have not been activated in response to an infection
- function: survey the body for infection
Effector lymphocytes
Activated lymphocytes that undergo proliferation and are specialized to perform a particular function
- effector function: how they eliminate pathogens from the body
Pathogen
Microbe that allows it to interfere with bodily functions and cause disease
Series of events that occur after pathogens adhere to epithelium
Skin wound allows pathogens to penetrate epithelium –> proinflammatory cyto/chemokines are released –> local infection, innate immunity –> DC take infection to lymph node and stimulate adaptive immunity –> effector cells and molecules of adaptive immunity travel to the infected tissue
B-lymphocytes (B cells)
B cell receptor is also referred to as an immunoglobulin (Ig)
- Soluble forms of BCRs referred to as antibodies
T-lymphocytes (T cells)
Surface expressed T cell receptor
- TCR is NEVER secreted
Structure of BCR and TCR
Variable region: antigen binding
Constant region: anchor the receptor to the cell membrane (associated with signal transduction proteins)
When the BCR is secreted as an _______, the constant region determines the effector function of the antibody
Antibody
What cell type is the bridge between adaptive and innate immunity?
Dendritic cells
Where do B cells and T cells develop?
Bone marrow; Thymus
What components of pathogens do antigen receptors recognize?
- Protein, carbs, and lipids
- Risk of developing cells that recognize self-protein/carbs/lipids
Macrophages and neutrophils have ____ with broad specificity to recognize multiple microbes and distinguish between self and non self
TLR (toll like receptor)
_____ and _____ come together to form antigen-binding site
Heavy and light chains
Do B and T cells recognize the same form of the same antigen?
NO, recognize different forms of the same antigen due to their effector functions
BCR recognizes ____ of an antigen
The native form
What part of the antigen do TCR recognize?
Peptides derived from the proteolytic degradation of the antigen
Pathway of TCR recognition
Native protein antigen –> denatured protein –> peptide antigens derived from denatured protein –> TCR bind to peptide:MHC molecule complexes
T cell effector function
To detect infected cells and provide activation signals to other leukocytes (controlling adaptive immune response)
How do dentritic cells activate adaptive immunity?
DC are present in tissues, along with macrophages
- when innate becomes overwhelmed, DC engulf pathogen and migrate to lymph nodes via afferent lymph vessels
- OR, pathogens can be carried to lymph nodes and then entangled by DC
- OR, pathogens in blood can be engulfed by DC in the spleen
Role of APC in activating adaptive response
Naive T cells entering lymph node can survey the antigens displayed by DCs
- antigen specific T cells will be activated to proliferate and differentiate into effector T cells
Effector T cells migrate to ____
Site of infection from the lymph nodes
Effector function
- activate macrophages to kill pathogens taken up by phagocytosis (helper T cells)
- kill infected cells (cytotoxic T cells)
What happens to the other portion of helper T cells (effector T cells)?
Remain in lymph node and provide activation signals to antigen specific B cells
Function of bone marrow and thymus
Maintain a steady state production of B and T cells with varying receptors
Dendritic cells
- Antigen processing: potent in activating T cells, degrade phagocytized pathogen and display a piece on the surface by MHC
- Antigen presentation
Dendritic cells provide the ____ and the ____ _____ for adaptive response
Antigen; activation signal
Major Histocompatibiliy Complex (MHC)
Complex of immune system genes that encode membrane proteins, which are involved in presenting peptides to T cells
Do MHC proteins have broad or specific specificity?
Broad, can bind peptides derived from many different pathogens
MHC class 1
Expressed on surface of most nucleated cells in the body
- recognized by cytotoxic T cells that express co receptor CD8
MHC class 2
Expressed on surface of 3 leukocyte lineages:
- DC, macrophages, B cells
- recognized by helper T cells that express co receptor CD4
Function of MHC class 1
Reports the “health status” of the cell
- proteins in the cell are degraded into short peptides after performing their function –> peptides are pumped into the ER and bound by newly synthesized MHC 1 proteins –> transported to cell surface
Viral proteins and MHC 1
Viral proteins can also be degraded in the cytoplasm and transported to ER –> bind to MHC 1 –> MHC 1-viral peptide complexes will accumulate on surface of the cell for recognition by virus-specific CTL (cytotoxic T cells)
Activation of CTLs
Activated in secondary lymphoid tissues by DC
- proliferate/differentiate to effector CTL –> enter circulation and are recruited to site of viral infection
- effector function: recognize/eliminate infected host cells
Function of MHC class 2
Extracellular pathogens!
- macrophage engulfs/degrades bacterium into peptides –> peptides bound by MHC 2 and transported to cell surface –> helper T cell recognizes complex and activates macrophage
- effector helper T cells are recruited to site of infection and will activate effector function of other leukocytes responding to infection (macrophages and B cells)
Effector helper T cell activation of macrophages
Some pathogens (listeria) can resist being killed in macrophage lysosomes and persist in cytoplasm - effector helper T cells activate macrophage production of powerful reactive oxygen species to kill intracellular bacteria
B cell response to infection in secondary lymphoid tissues
Antigen binds to B cell receptor –> facilitates internalization of the antigen for processing and presentation by MHC 2 proteins
- activation by effector helper T cells will induce B cell proliferation/differentiation to plasma cells
- plasma cells synthesize and secrete original antigen receptor as antibody
Effector helper T cell activation of B cells
Cell-surface immunoglobulin of B cell binds to bacteria –> cell engulfs and degrades them = peptides –> bacterial peptides bound by MHC 2 in endocytic vesicles –> bound peptides transported by MHC 2 to the cell surface –> helper T cell recognizes complex of peptide antigen with MHC 2 and activates B cell
Do B cell receptors and antibodies recognize native protein antigens?
Yes, DC can release unprocessed antigens that are recognized by B cells in addition to processed/presented antigens recognized by T cells
____ signals are required for lymphocyte activation
2; important mechanism of peripheral tolerance (tolerance to self protein)
Signal 1: recognition of antigen
Signal 2: delivered by another cell in form of cytokines and surface proteins
Antigen-activated T cells require a second signal provided by ____
Dendritic cells
Antigen-activated B cells require a second signal provided by ______
Effector helper T cells
DC and effector T cells must become ____ before they can activate mature T cells
Licensed (must have taken up a pathogen)
Once B cells are activated by antigens, they have ______ to collaborate with helper T cells or they become unresponsive
24 hours
