Exam 4 Lecture 26 Immune/endo/CNS Flashcards
Leukocytes and Neutrophils
Produced in bone marrow.
Functions:
1. phagocytosis
2. Release chemicals involved in inflammation (vasodilator, chemotaxins, etc.)
Basophils
Produced in bone marrow
Have functions in blood similar to those of mast cells in tissues
Eosinophils
Produced in bone marrow
Functions:
1. Destroy multicellular parasites
2. Participate in immediate hypersensitivity reactions
Monocytes
Produced in bone marrow
Functions
1. Have functions in blood similar to those of macrophages in tissues
2. Enter tissues and are transformed into macrophages
Lymphocytes
Mature in bone marrow (B cells and NK cells) and thymus (T cells); activated in peripheral lymphoid organs
Function:
serve as “recognition cells” in specific immune responses and are essential for all aspects of these responses
B cells
Mature in bone marrow; activated in peripheral lymphoid organs
Functions:
1. initiate antibody-mediated immune responses by binding specific antigens to the B cell’s plasma membrane receptors, which are immunoglobulin
2. During activation are transformed into plasma cells, which secrete antibodies
3. Present antigen to helper T cells
Cytotoxic T cells (CD8 cells)
Mature in thymus
Functions:
bind to antigens on plasma membrane of target cells (virus-infected cells, cancer cells, and tissue transplants) and directly destroy the cells
Helper T cells (CD4 cells)
Mature in thymus
Functions: Secrete cytokines that help to activate B cells, Cytotoxic T cells, NK cells and macrophages
NK cells
Mature in bone marrow
Functions:
1. Bind directly and nonspecifically to virus-infected cells and cancer cells and kill them
2. function as killer cells in antibody-dependent cellular cytotoxicity (ADCC)
Plasma cells
Produced in peripheral lymphoid organs; differentiate from B cells during immune responses
Secrete antibodies
Macrophages
Produced in bone marrow, reside in almost all tissues and organs; differentiate from monotypes
Functions:
1. Phagocytosis
2. Extracellular killing via secretion of toxic chemicals
3. Process and present antigens to helper T cells
4. Secrete cytokines involved in inflammation, activation and differentiation of helper T cells, and systemic responses to infection or injury (the acute phase response)
Macrophage-like cells
Almost all tissues and organs; microglia in the CNS
Functions: same as macrophages
Mast cells
Produced in bone marrow; reside in almost all tissues and organs; differentiate from bone marrow cells
Functions: release histamine and other chemicals involved in inflammation
What stimuli does immune system respond to?
Bacteria, viruses, tumors and other antigens
What happens when immune system is stimulated?
Cell- mediated or numeral immune responses are activated and this information is sent to the hypothalamus by cytokines and peptide hormones secreted from cells of the immune system
How might immune system signaling and activation be communicated to the nervous system?
Through the release of peripheral soluble factors (particularly cytokines) by cells of the immune system. These factors function as hormones to affect the CNS.
How can peripheral soluble factors affect the CNS?
Directly by crossing the BBB or indirectly by stimulation of the vagus nerve
Two types of signaling molecules between immune and CND or PNS?
Cytokines or chemokines
How can cytokines directly influence the electrophysiological function of neurons in the CNS or PNS?
During inflammation of the brain or PNS
What is the family of chemokines associated with?
The trafficking of leukocytes in physiological immune surveillance and inflammatory cell recruitment in host defense.
How are chemokines expressed in CNS?
constitutively by microglia cells, osteocytes and neurons and their expression can be increased after induction with inflammatory mediators.
What in CNS can chemokines modulate?
Neuronal signaling through the inhibition of neuronal calcium currents
Four cytokine categories
- Inflammatory cytokines
- immunomodulatory cytokines
- chemokines
- Growth factors and other mediators`
What can cytokines released by immune system influence in CNS?
Cognitive processes, central neurotransmission and the function of the PNS
Which cytokines and neuropeptides have effects on behavior that is mediated by the CNS?
Those secreted by peripheral immune cells
How can pro=inflammatory cytokines activate the hypothalamus-pituitary-adrenal axis and induce sickness behavior during the acute phase response?
Fever, sickness behavior, depressive effects on social behavior
What organs are affected by systemic response to infection or injury?
Brain, Liver, Bone marrow, Adipose tissue, muscle, hypothalamus, anterior pituitary, adrenal cortex
What happens immediately after microbe infection or injury?
Monotypes and macrophages secret IL-1, TNS and IL 6, which increases Plasma IL-1, TNS and IL-6
How do IL-1, TNF and IL-6 affect the brain?
Fever, decreased appetite and food intake, sleepiness, fatigue
How do IL-1, TNS and IL-6 affect the liver?
Liver retains Fe, Zn, secretes acute phase proteins. All these things change in plasma.
How do IL-1, TNS and IL-6 affect bone marrow?
Cause production and release of leukocytes and increase in blood leukocytes
How do IL-1, TNS and IL-6 affect adipose tissue?
Increase lipolysis and increase plasma free fatty acids
How do IL-1, TNS and IL-6 affect muscle?
Increase in protein breakdown and aa release. Increase in plasma amino acids.
How do IL-1, TNS and IL-6 affect hypothalamus and anterior pituitary? Adrenal cortex?
ACTH secretion increases as well as plasma ACTH. Adrenal cortex increases cortisol secretion. Plasma cortisol increases.
How do cytokines work on endocrine glands?
Cytokines act directly on endocrine glands such as the pituitary, thyroid, pancreas, Adrenals and gonads and alter their secretions.
How do pituitary hormones influence immune function?
Pituitary hormones and secretions of their peripheral target endocrine glands may modulate immune function.
How ACTH/glucocorticoids related to immune system?
They are immunosuppressants
How do GH and prolactin influence immune system?
Gh and Prolactin may potentate immune responses through a variety of effects and can stimulate growth and activity of the thymus gland.
What do cognitive stimuli like stress stimulate?
neuroendocrine pathways GH, PRL, and adrenal, Gonadal and thyroid hormones, trophic hormones
What effect do adrenal, Gonadal and thyroid hormones and trophic hormones have on B and T cells?
They can up or downregulate them.
What effect can GH and PRL have on T cells?
Unregulate them.
What can T cells stimulate?
cytokines
What effect do adrenal, Gonadal and thyroid hormones, trophic hormones have on thymus?
Unregulated the secretion of thymic hormones.
What do thymic hormones stimulate?
T cells and cytokines
How do thymic hormones affect brain?
Provide feedback
How do T cells affect brain?
Provide feedback via proteins ad peptide hormones secreted by immune cells
What do non-cognitive stimuli, like antigens, stimulate?
The release of macrophages, which stimulate cytokines
How do we know that the hypothalamic-pituitary-adrenal axis affects the immune system?
Surgical removal of pituitary lad to reduced antibody responses. GH treatment restored antibody production.
How does ACTH influence immune system?
There are ACTH receptors on both B. ad T cells. ACTH also reduces antibody responses in vitro and reduced IFN-gamma (interferon) production
What stimulates prolactin synthesis in hypothalamus?
Suckling stimulus, sleep, stress
How does TRH or (VIP) from hypothalamus influence release of prolactin?
Unregulated it
How does dopamine or somatostatin influence prolactin release?
downregulates it
How do estrogens influence pituitary prolactin release?
It unregulated it
What kind of feedback does pituitary provide hypothalamus regarding prolactin?
Negative feedbac
How does prolactin affect immune system?
Lymphocytes: regulation, e.g. Nb2 cells
Hypothalamus-pituitary-adrenal axis
- hypothalamic releasing factors: CRH and vasopressin
- Pituitary secretes corticotropin (ACTH) to stimulate adrenal cortex
- Adrenal gland releases steroid hormones
- Feedback inhibition by cortisol of monocyte and TNFalpha, IL-6, IL-2, IL-1 release and of macrophages and IL-1-RA release
Following injury or response to infection, what do cells in local tissues release?
Cytokines that travel via the bloodstream to the liver and the CNS
How else might information about injury be sent to CNS?
Via affront neural pathways, including the vague nerve and nociceptive fibers
What does activation of the HPA by IL-6 (cytokine) do?
Increase the secretion of adrenocorticotropin (ACTH), which in turn increases cortisol release from the adrenal cortex.
What does increased activity along sympathetic nerves do?
It enhances the release of epinephrine from the adrenal medulla
What kind of immune activity do cortisol and EPI perform in bloodstream?
anti-inflammatory
Of what do IL-6 and other cytokines stimulate the production of?
Acute phase proteins. They also activate the other features of the acute phase response.
What does efferent activity along the vague nerve release?
Acetylcholine, which inhibits the production of tumor necrosis factor (TNF) and other pro-inflammatory molecules by Kupffer cells and other tissue-resident macrophages
How do cytokines activate pituitary croticotrophs?
In a corticotroph, specific binding of selected cytokines to gp130-linked transmembrane spanning receptors mediates activation of JAK-STAT pathway, increased POMC gene transcription, and increased ACTH secretion.
What does increasing circulation of EPI do response to an endotoxin by immune system?
It converts an inflammatory (TNF dominant) response to anti-inflammatory (IL-10 dominant).
What anti-inflammatory properties does ACTH have?
ACTH, cortisol and the synthetic analogs of cortisol have the capacity to prevent or suppress the development of local heat, redness, swelling, and tenderness by which inflammation is recognized at the gross level of observation.
How do ACTH and its analogs prevent inflammation?
At the microscopic level, they inhibit early phenomena of inflammatory process (edema, fibrin deposition, capillary dilatation, migration of leukocytes into the inflamed area, and phagocytic activity). Also later manifestations (capillary proliferation, fibroblast proliferation, deposition of collagen, and still later, cicatrization)
Inflammation axis
- Stimulus: bacteria, virus, fungus, trauma, immune challenge
- Primary inflammatory: cytokines (IL-1beta, TNF-alpha)
- inflammation
What is produced during inflammatory response?
- IL-1beta, TNF-alpha, More cytokines
- eicosanoids (prostaglandins leukotrienes)
- platelet activating factor
- Neuropeptides
- Various other mediators
How do inflammatory agents influence HAP?
Hypo releases CRH and LHRH
Pituitary releases ACTH, gonadotropin, TSH, prolactin, growth hormone
Adrenal releases cortisol and catecholamines
How do inflammatory agents influence liver?
Produces acute phase proteins
How do Gonadal steroids influence immune system and regulation of neuronal gene expressions?
Androgens generally exert suppressive effects on both humoral and cellular immune response and seem to represent natural anti-inflammatory hormones.
Estrogens, on the other hand, exert immunoenhancing activities, at least on humoral immune response
What kind of sexual dimorphism exists within the immune system?
Females have higher levels of IgG, IgM and IgA than males.
In what gender is antibody response to antigen greater in magnitude?
Females. More prolonged, too.
How much more autoimmune disease do females experience?
Two to tenfold higher incidence
How do testosterone and estrogen alter disease progression?
Manipulation of testosterone or estrogen alters autoimmune disease progression or onset in animal models.
