Lecture 4 - Adaptive Immunity Flashcards
Hematopoietic Stem Cell differentiation
Stem cell in bone marrow that differentiates to:
— Myeloid Progenitor Cells (which mostly differentiate to innate immunity cells)
— Lymphoid Progenitor Cells (which mostly differentiate to adaptive immunity cells)
Myeloid Progenitor Cell differentiation
— RBCs
— Platelets
— Neutrophils - innate immunity
— Eosinophils - innate immunity
— Basophils - innate immunity
— Monocytes - innate immunity
Monocyte differentiation
— Dendritic cells
— Macrophages
Lymphoid Progenitor Cell differentiation
— T Lymphocyte - adaptive immunity
— B Lymphocyte - adaptive immunity
— Natural Killer Cells - innate immunity
T Lymphocyte differentiation
— Helper cells
— Regulatory cells
— Cytotoxic cells
B Lymphocyte differentiation
— Plasma cell to detect antibodies
Adaptive immunity
Immune response mediated by B and T lymphocytes (B cell/ T cell) to infectious agents and noninfectious molecules
Responses are generated in response to antigens
Innate vs Adaptive immunity
Innate:
- Detects common microbial
structures
- Receptors are encoded in the
germline
- Same response upon repeat
exposure
Adaptive:
- Detects vast repertoire of
molecules
- Receptors generated by somatic
recombination
- Improved “adapted” response to
repeat exposure
Antigen (Ag)
A molecule, typically from a pathogen, that is recognized by an antibody
Types of Antigens recognized by B cells
- Proteins
- Lipopolysaccharides
- Lipids
- Nucleic acids
Types of Antigens recognized by T cells
Peptides derived from Proteins
T Lymphocytes (T Cells)
Adaptive immunity cells that require antigen presentation by dedicated antigen presenting cells (APC)
T cells require co-receptors to assist antigen recognition
Antigen Presenting Cells (APC)
Cells that present antigens that can be recognized by T cells
Reside in potential sites of Microbe entry (skin, G.I. tract, respiratory tract, etc.). APCs capture, process and present antigens to T lymphocytes in peripheral lymphoid tissues
TCR
T Cell Receptor
A single TCR recognizes a single presented antigen
B Lymphocytes (B Cells)
Adaptive immunity cells with BCRs that directly recognize its cognate antigen
There are millions of B cells each with a unique BCR
Two forms of Adaptive Immunity
- Humoral Immunity
- Cellular Immunity
Humoral Immunity
Type of adaptive immunity
Directed against extracellular microbes and mediated by B lymphocytes.
B lymphocytes secrete antibodies that neutralize and eliminate microbes and microbial toxins
— Microbe: extracellular microbes
— Responding lymphocytes: B lymphocyte
— Functions: block infections and eliminate extracellular microbes
Cellular Immunity
Type of adaptive immunity
Directed against intracellular microbes and mediated by T lymphocytes.
T lymphocytes activate phagocytes and lymphocytes or kill infected host cells
— Microbe: phagocytosed or intracellular microbes
— Responding lymphocytes: helper or cytolytic T lymphocytes
— Functions: activate macrophages to kill phagocytosed microbes or kill infected cells and eliminate reservoirs of infection
Phases of the Immune Response
- Recognition: Naïve lymphocytes recognize corresponding antigen
- Activation: Lymphocytes differentiate and start clonal expansion
- Effector phase. Differentiated lymphocytes initiate microbial elimination
- Decline: After microbial elimination the
signal for lymphocyte activation disappears.
Most of the cells activated by antigen die by a process of programmed cell death (apoptosis) - Memory: The remaining cells are memory
lymphocytes, which may survive for months or years
Two signals for activation
Signal 1: Antigen receptor binds antigen
Signal 2: Microbial or innate immune signals
BCR
B Cell Receptor
Recognizes a distinct microbial 3-dimensional structure
Each recognize a limited number of antigens
Clonal expansion
When a BCR or TCR detects antigen the B cell or T cell undergoes multiple rounds of cell division, thereby expanding. Each daughter is identical to the parent cell, i.e. a clone
The Memory Phase
Prior exposure to one antigen results in stronger responses to subsequent challenges with the same antigen
Naïve B cell
A B cell that has never previously
encountered its target structure
The BCR is restricted to the plasma membrane of the B cell
Activated by antigens and other “second” signals
B cell activation
Results in their proliferation (clonal expansion) and differentiation into effector cells that actively secrete antibodies.
BCR production is now modified so that the BCR is secreted as an antibody
Antibody (Ab)
A secreted BCR from B cells that recognize antigens
Released into circulation and mucosal
fluids by B cells upon infection
Neutralizes microbes and microbial toxins
Stops microbes from gaining access to or
colonizing host cells.
Does NOT have access to intracellular microbes
CD4+ helper T cells
They detect antigens presented by professional Antigen Presenting Cells
They secrete cytokines to activate other components of the immune response (Macrophages, B cells etc.)
CD8+ cytolytic T cells
They detect microbial antigens presented by all nucleated cells and destroy the presenting cell
The Lymphatic System
A network that transports fluids from tissues through lymph nodes and then to the circulatory system.
Excess interstitial fluid is collected by the lymphatic system and is processed by lymph nodes, then deposited into the circulatory system.
Unlike the circulatory system, the lymphatic system is not closed and has no central pump
Lymphatic System Processes
- Some APCs drain from peripheral tissues into lymph nodes.
- T lymphocytes enter lymph nodes.
- APCs activate T Lymphocytes
- Lymphocytes exit lymph nodes and enter circulation, then exit circulation into inflamed tissue where they mediate microbial destruction
Lymph node
A secondary lymphoid organ with regions that are rich in certain cell types
Components:
- Afferent lymphatic vessels (for entry)
- Cortex (B cell rich)
- Paracortex (T cell and DC rich)
- Medulla
- Efferent lymphatic vessel (for exit)
