Immunology From Birth To Death Flashcards
What receptor is the most important receptor for passive transfer of maternal antibodies in utero
Neonatal Fc receptor on the placenta
- allows for passage of ONLY IgG though (really likes IgG1 subtype the most)
- if not present = IgG degrades in the placenta a naturally
Humoral protection in neonates
Overall child’s own antibodies dont get up to effective levels until 1-2 years old with vaccination and 4-10 yrs old without vaccination
Maternal antibodies protect until 12 months of age almost exclusively
- this is why breast feeding is important for IgG and IgA
In newborns = exclusively IgG
IgA and IgM production begins at 4-6 months
What is the window of susceptibility
Begins around age 2months -> 2 years
- due to transient hypogammaglobulonemia that initiates at approximately 3-4 months of age
- increased susceptibility to infections due to maternal antibodies disappearing and being replaced by neonatal antibodies (this transitional state results in increased risk)
How does IgA get passed to fetus
The polymeric immunoglobulin receptor (pIgR) located on maternal breast tissue endocytosis sIgA via binding of the J-chain into breast milk which is then secreted into neonate during feeding
The IgA produced by maternal gut infections helps shape the neonatal gut micro iota similar to mother/healthy adult
- also lowers risk of necrotizing enterocolitis
What is immunological blunting
Maternal IgG binds to inhibitors receptors on B-cells which inhibit antibody functions
- this results in neonatal B-cells skewing towards memory Bcells vs CD4 plasma B cells
- *this however results in weakened vaccine responses since the maternal antibodies can link the antigens of the vaccine and inhibit production of antibodies**
- can occur up to one year total depending on high level of antibodies in mom
Other immune components of breast milk
Neutrophils and lymphocytes and macrophages
- macrophages = 80%
Cytokines
Lactoferrin B
- enhances PMN action against gram +/-
Lysozyme
- antimicrobial agent against gram +
T-cell immunity in neonates
Impaired TH1 response
- produce less IFN-y and TFN-a so results in TH2 response more
Less efficient CD8 T cell response
- reduced perforin levels and CD28 expression
Immature APCs
- less CD80/86 and CD 40
- reduce production of TLRs
- lower expression of MHC
- less cytokines
25% PMNs compared to adults
- less respiratory burst
- less lactoferrin
- less selections and B-integrins
Presence of gramma-delta T-cells (super immature T cells that the neonate uses for skin and mucous membrane immunity)
- like 60% normal CD8 T cell activity
while they are weak against all pathogens, intracellular pathogens give neonates the most trouble
this does have a postive though of allowing the neonate to develop tolerance for self antigens, environmental antigens and gut microbiome that it needs to survive
Steps of the “typical” immune response
1) invasive by the pathogen and immune response
2) APC activation and upregulation of T-cells to either/both CD4 and CD8 cells
3) immune clearance of a pathogen
- CD8 = lysis
- CD4 = phagocytosis via macrophage action or antibodies via plasma cell activation
4) M1 -> M2 macrophage transition (start repair and is caused by Treg cells)
- also memory B cells start to form
Immunological memory
1) antigen recognition via APC: T/B cell interactions
2) lymphocyte activation = clonal expansion occurs and differentiation into plasma cells or CD4 T cells occurs
3) antigen elimination together
4) contraction occurs with macrophages which kills off nearly all clones but keeps roughly 10% left to become “memory cells”
this is what results in a much larger and stronger antibody titer and overall immune response to consecutive exposures to antigens
Immunosenescene
Changes in the immune cell functions and composition that results in senescent changes (cell arrest)
Common cause of gaining immune systems
The immune cells slowly become less responsive to growth stimuli and cease replication in the G1 -> S phase checkpoint
Triggers (more exposure = faster speed up)
- replication stress
- oncogene activation
- oxidative stress
- chemo and radiation
Causes:
- increased autoimmunity
- increased infection
- “inflammaging” (chronic low levels of inflammation at all times)
- decreased overall activity
- cytokine changes
How do each part of the immune system change in immunosenescent stages
1) B cells
- increases auto-antibodies and TLR stimulation
- increases IL4/10 and TFNa
- decreases overall number, activation and efficacy of their antibodies
2) dendritic cells
- increased auto reactivity
- decreased phagocytosis and lymphocyte activation
3) T cells
- decreased everything pretty much
- decreased CD28 and overall numbers and activity
4) neutrophils
- decreased chemotaxis
- decreased phagocytosis and proteolytic enzyme secretion
5) NK cells
- decreased cytotactic and chemo tactic secretions
- decreased cytotoxicity and senescent cell clearance
6) macrophages
- increases pro-inflammatory cytokines and senescent bystander effects
- alters the M2 phase macrophages and increases pro-infalmmatory markers
Thymic involution in aging
Begins at age 30 roughly and start to see a decrease in naive T:memory T ratio occurring
Overall thymus atrophy occurs and increases in perivascular spaces occurs and is replaced with adipose tissues
*this results i decreased everything in T-cells and is the hallmark for gaining immunosystems lessened ability to mount an innate reaction**
also is the main cause of inflammaging since there is less capacity for autoimmune suppression due to lack of Treg cells, increased self-reactive T cells, reduced naive T cells and excessive senescent somatic cells
Inflammaging
Chronic autoreaction of the immune system to ones own body done in aging
- is due to Thymic involution resulting in less naive T cells but more reactive T cells
- also increased macrophage autoreactivity occurs
Pro inflammatory cytokines (IL-1/6 and TNF-a) go up while IL -10 goes down (anti-inflammation)
- *is an assocated cause of**
- all age related diseases
- sarcopenia
- osteoporosis
- metabolic syndrome
- cancers
- neurodegenerative diseases
- etc.
Immunosenescence and vaccines
Results in decreased leukocyte migration and diminished APC
- this results in decreased everything downstream and causes tow main issues
1) less response to vaccine (so not as effective)
2) can induce a stronger reaction (due to autoreactivity already in place and decreased ability of the immune system to actually get rid of the antigen altogether)
