Addaptive Immunology Flashcards
Adaptive immune system function
Creates immune response to specific antigen
What is an antigen
Foreign protein or other molecule that is the target of an immune response
Adaptive immunity cells
- antigen presenting cells (APCs) present antigen complexed with MHC (major histocompatability) class II proteins on cell surface
Occurs in lymph nodes, leads to cytokine signaling and lymphocytes activation - T lymphocytes
Helper T cells (CD4+) or cytotoxic T cells (CD8+) - B lymphocytes
Memory B cells, plasma B cells
B lymphocytes function
Memory B cells- secondary immune response to same antigen
Plasma B cells- make antibodies, bind to specific antigen
Two types of adaptive immunity
Humoral immunity- fights invaders outside cells (bloodstream)
- bacteria and toxins
- involves plasma B and antibodies
Cellular immunity- attacks antigens found inside cells
- virus, fungi, parasites
Involves cytotoxic T cells and natural killer cells
What happens when B cells activate
Undergo clonal expansion (proliferation) producing plasma cells and memory cells (long lived)
What can activate B cells
T independent antigens activate B cells directly
T dependent antigens require activation of helper T cells that produce cytokines to activate B cell indirectly
T-independent = direct activation
T- dependent - indirect activation
What determines t-dependent or independent
Type of antigen
Amount present
Where do antigen-antibody complexes go
Cleared by complement cascade or
Liver or spleen
What is co stimulation of B cell
- Antigen bind to B cell receptor
- T cell receptor interacts with antigen presenting MHC class II protein
- two signals for B cell to become activate and mature into plasma cell
Why is co stimulation of B cell important
Two signals to all B cell activation and mature
Ensure that the B cell activation is required, not an oops with correct antigen binding or an oops with TCR binding to MHC II
Prevent immune overdrive
Plasma B cell creation stages
- Stem cells differentiate into mature B cells, each bearing surface immunoglobulin against specific antigen- checks that receptor shape doesn’t target body cells, and that it targets antibody effectively- after success CLONE EXPANSION of specific antibody
- B cell encounters specific antigen and proliferates (into plasma and memory)
3a. B cells proliferate into long lived memory cells (these memory cells can be used at a later date, stimulated by antigen, become plasma cell)
3b. Plasma cells secrete antibodies into circulation
Acquired immunity: antigen-specific responses
All responses result in antibody binding to antigen
1. Agglutination: clumping of bacteria so all in localized region, easy antibody pick up
2. Opsonization: coat antigen with multiple antibodies enhances phagocytosis, easier for macrophage to engulf
3. Neutralization: blocks adhesion of bacteria/virus to mucosa and blocks attachment of toxin. Antibodies bind to virus, bacteria, toxin
4. Antibody-dependent cell-mediated cytotoxicity: used for parasites (large bad cells) can’t engulf. Antibodies coat the parasite allowing macrophages, eosinophils, natural killer cells to destroy using lytic enzymes, perforin
5. Activation of complement: protein binds to antibody on bacteria, put holes in bacteria cell wall, cause inflammation and cell lysis
Where are T cells produced and matured
Produced in red bone marrow
Mature and undergo ‘thymic selection” in the thymus
Function of T cell receptor
Antigen binds- every T cell has one specific antigen
How are T cells activated
Antigen presenting cell (APC) that has antigen complex with MHC II- could be B cell in t-dependent, dendritic cell, infected body cell
How are different T cells made and what MHC do they interact with
CD4+ and CD8+ are receptors
CD4+ T cells become helper T cells. Interact with MHC II present on APCs or MHC I on infected cells
CD8+ T cells become cytotoxic T cells. Interact with MHC I found on all nucleated cells of body (not RBC)
What other things can helper T cells become
Memory T cells
TH cell activation
- An APC encounters and ingests a micro-organism. Antigen is enzymatically processed into short peptides which combine with MHC class II molecules and are displayed on surface of APC
- TCR on surface of CD4+ helper cell binds to MHC antigen complex. TH cell or APC is stimulated to secrete co-stimulatory molecule. (Co-stimulatory molecule required to activate T cells that have not previously encountered antigen). Two signals activate TH cell produce cytokines
- Cytokines cause TH cell to activate
TC activation
- Virus-infected cell or cancer cell (MHC class I body cells) produce abnormal endogenous antigens
- Abnormal antigen is presented on cell surface in association with MHC class I molecules. Binding of TH1 cell to MHC class I antigen presenting promotes secretion of cytokines
- Cytokines activate a precursor CTL which produces a clone of CTLs (cytotoxic T cell activation)
- CTL induces destruction of the virus-infected cell by apoptosis
T cell precursor differentiation
- ? Somehow -> natural killer cells -> kill antibody coated cells or bacteria, MHC class I APC
- Migrate to thymus -> cytotoxic T cells -> kill MHC class I APC
- Migrate to thymus -> helper T cell -> bind to MHC class II APC or MHC class I antigen infected cell -> secrete cytokines that activate other immune cells
Pathway of complement activation
Antibody binds to antigen and activates C1
C1 splits and activates C2 and C4
C2a+ C4b come together -> C3
C3 split into C3a + C3b (diff jobs)
C3a- function inflammation
C3b- function in cytolysis and opsonization (coating pathogen)
Outcomes of complement activation
Cytolysis (apoptosis)
C3b activate C5
C5 split C5a + C5b
C5b activates C6
C6, C7, C8, C9 get together, form ring, enter pore -> apoptosis
Opsonization
C3b act like antibodies and coat. Makes life easier for macrophage/ phagocyte to locate and engulf
Inflammation
C3a binds to receptor of mast cells -> Histamine release
And
C3b -> c5 -> C5a + C5b -> C5a bind to receptors of mast cells -> histamine release
What happens without immunity
Graph # of micro-organisms vs duration of infection (t)
- lacking innate - no physical/chemical barriers, huge increase in micro-organisms
- lacking adaptive - still have barriers working, but overtime invaders increase and no antibodies or T cells to remove them
- normal human graph a parabola- down as recovery
Interferons creation and use pathway
- Viral RNA from an infected virus enters the cell
- Virus induces the host cell to produce interferon mRNA (IFN-mRNA) which is translated into alpha and beta interferons
- Interferons make contact with uninflected neighbouring host cells -> bind to plasma membrane or nuclear receptors. Interferons induce the cells to synthesize antiviral proteins (AVPs)
- AVPs degrade viral mRNA and inhibit protein synthesis (outcome- interfere with viral replication)
- interferons made in infected cell
- interferons make uninfected cell synthesize antiviral proteins
- by the time cell becomes infected, AVP will degrade viral mRNA
