Factors Affecting Immune Response Flashcards
key early set of cytokines in infection are?
What do they do
- Proinflammatory: (IL-1, IL-6, TNF-a)*
- THese are triggered early in response to infectious agents and/or tissue damage and they:*
- Upregulate the induction of acute phase proteins in the liver to increase the complement factors
- Temperature (fever) and behavioural changes (sleep, withdraw from others, energy distribution to facilitate healing);
- induces fever response, enhances metabolic rate and make temp less desirable for pathogenic
- TNFa triggered by bacterial LPS
- Tissue repair: via a number of processes
- bone reabsorption
- fibroblalst prolif
- collagenase synthesis
- leukocyte adhesion
- T and B cell activation for adaptive immune response!
chemokines and interferons in infections???
Chemokines: Ensure neutrophils and lymphocytes get to where they are needed in infection.
- Aid Chemotaxis (eg; neutrophils)
- Direct effector cell traffic
Interferons: vital in viral infections
- triggered by infection
- released to induce a transient ‘antiviral state’
- Activate NK cell activity
- Upregulate HLA expression (improves cytotoxic T cell killing)
What produces the different cytokines???
Proinflammatory cytokines: produced from dendritic and APC cells
Everything else: produced from CD4 T cells (activated to produced different sets of cytokines to produce different outcomes)
- start as naive CD4 T cells, the context of determines them to either be
- Type Th1 cells: activate and respond to IgM, IgG, cytotoxic T cells and acute virus and bacterial infections
- Type Th2 : produce and activate things that deal with mucosal immunity and chronic infections, especially parasites, as well as IgA and IgE
- Type Th17: mucosal immunity and inflammatory processes
- Type Treg: down-regulate and balance other classes
- We usually always get a mix with a push in one direction of Th1 and Th2
What changes have affective our immunity and the dominanting health issues?
- Our change from a primitive to modern environment: a change to cramped living conditions
- Microbiological and environmental antigen exposure has greatly changed; in a relatively short amount of time, so maybe we don’t deal with it very well
- The sort of antigens and the exposure has also change
- Primitive Human Environment:
- Diverse ranfe of environ and microbial antigens
- Restricted environmental antigen range
- Parasites
- Modern Human Environment:
- LESS Diverse environmental and microbial organisms
- MORE restricted environmental antigen range
- VIRTUAL ABSENCE of parasites (especially in developed countries)
How can we explain the changes in disease distribution?
- Due to the rapid change in our antigen and microbial, our evoutionary Immune Response cant keep up!!
- Therefore we tend to develop less of a regulatory T cell response. As a consequence, Th1, Th2 and Th17 don’t get controlled as well as they should, and we end up with
- ALLERGIES
- Autoimmunity and inflammatory diseases
- Therefore the change in disease distribution can be explain by the balance of T cells sub groups
What’s a common clinical appearance of a baby with Immunodeficiency SCID
- Reccurent infections of these types in the first few months
- Blood cells, platelets etc : normal
-
White cell count, especially lymphocytes: LOW
- NO CD3 (T Cells) ‘SCID’
- Almost ALL LYMPHOCYTES HAVE CD20 (B cell marker)
- Congenital/primary Immunodeficiency
What is SCID and was is it so severe?
Severe Combined Immunodeficiency
- Absence of T cells (No CD3 lymphocytes)
- With no T cells you cannot make both helper and cytotoxic T cells and therefore have no immune response
Describe Congenital/Primary Immunodeficiencies..
- Very RARE genetic mutations
- Exception: Selective IgA deficiency, which is common (1/500), often asymptomatic
- In Utero Defects/disease
Describe the more common ‘Acquired or Secondary’ Immunodeficiency
- Infection (eg; HIV)
- Drugs (eg; steroids and cytotoxic drugs): by altering aspects of immune function (eg B cell and T cell proliferation)
- Systemic Disease (renal failure, malnutrition, malignancy, burns): produce factors that diminish immune responsiveness
If you have a Pimary Immunodeficiency, it’s always going to manifest in a young person as __________.
Describe the organisms and from this what could be the Immune issue
Just know the spectrum gives you information on the issue
Revealed by Recurrent Infections
- Extracellular Bacteria (streptococci)
- IgM and IgG, complement, phagocytosis
- Intracellular Bacteria (tuberculosis)
- T cells, macrophages
- Viruses (measles)
- T cells, IgG, IgA, interferon (complement)
- Parasites (ascaris)
- IgE, Eosinophils, mast cells, T cells
- Fungi (candida)
- T cells, IgA, neutrophils
The timing of symptoms is a consequence of ______
What happens in early life
- In utero, we live in a relatively sterile environment, so as we develop our IS, we make little antibodies. We get most of our antibodies as maternal IgG via the placenta
- Post birth, we have a ‘top-up’ of IgA fro breast milk, so in the first few months our antibodies are maternal (first 6 months)
- We would be protected from infections
- As time passes we start to build up our own antibodies as a response from our external environment, and our maternal load diminishes
- HERE is when congenital immunodeficiencies become evident
- Why Live viral vaccines are not given until lter
Antigen considerations
- Antigen shape
- If very different to self: Good response
- But if similar to self: poor immune response
- HLA affects what antigens we present, and therefore determines how well we respond to things
- some people may respond purely to some pathogens purely because of their HLA haplotype, and NOT from any immunodeficiency
Antibody considerations?
- Effectiveness of opsonisation affects response kinetics
- The quicker you get rid of an antigen the less time you have to generate an efective immune response
- Further responses to activate B cells
- First class produce IgM → then later switches to IgG
- Promoted by high [IgM], diminished by high [IgG] so that you don’t ‘overdo it’
We sense the external world (via 5 special senses) and the internal world via….
-
interoceptors for pain, temp, visceral activity, hunger, thirst, O2
- Senses physical world in order to maintain an adequate relationship with it
-
IMMUNE SYSTEM that senses shape
- senses microbial world and maintains relationship with it
These two systems interact and are called the Neuroimmune Network
Describe the Neuroimmune Network
- Comprised of 3 Components
- Autonomic NS: affect Endocrine and immune via nerves
- Endocrine System: affects immune system via hormones
- Immune System: affects endocrine and brain via cytokines (immune hormones)
Autonomic Nerves and Lymphnodes?
- There is large Autonomic sympathetic nerves going into our secondary lymphoid organs
- Predominately in the Para-cortical region where T cells CD4 reside and mature and respond to antigens
- Use Norepinephrine to communicate
Actually have extensive innervation of ALL lymphoid organs
- Predominately Sympathetic (NE)
- Terminatein Tcell rich areas
- Density related to Social temperament
Describe this picture in terms of the interconnection between the Nervous and Immune system
THe imune system evloved in order for us to realise many different shapes, and responds to infection or tissue damage.
As a consequence of that, some of the products of this (particularly pro-inflammatory cytokines) have influences OUTSIDE that network that affect especially the nervous system predominately to alter a whole range of otehr factors
On the other hand the Nervous system via ANS and hormonal axis influences immune behaviour, energy distribution to facilitates recovery. Also produces Cortisol, ACh and NE that alter our immune response.
The way we think/feel/behave can therefore influence the way we respond to pathogens “Psychosocial Factors”
If 4-fold or greater you’ve effectively responded to vaccine
Caregivers didnt respond as well, potentially due to the behaviours/perceptions were altering the neuroimmune network feeding different signals into the 2<span>o</span> lymphoid organs that stops them being as effective
