NPB 101- Exam 4 (Final)

The Thyroid Gland

-situated in our neck, over trachea
-contain follicular cells

Follicular cells

-thyroid hormone secretion cells
-form spheres that surround an inner lumen that is acellular that consists of colloid

Colloid consists..

Mainly of thyroglobulin, a large protein where thyroid hormone synthesis takes place

Thyroid hormones synthesis

-made of tyrosine & iodine
-iodine cannot be made in the body

Thyroid hormones synthesis pt.2

-reduced to iodide before absorption in the small intestine
-taken up & converted into thyroid hormone by the thyroid gland

2 active forms of thyroid hormone

-tetra-iodothyronine (Thryroxine), T4
-tri-iodothyronine (T3)

Major effects of thyroid hormone

-increase metabolism
-increase rate of O2 consumption
-increase heart rate, strength of contraction

Hypothyroidism (too little thyroid hormone)

-reduced BMR
-poor tolerance of cold
-tends to increase weight
-easily fatigued

Hyperthyroidism (too much thyroid hormone)

-elevated BMR
-excessive perspiration, poor tolerance of heat
-reduction in body weight

Goiter

-can occur w/ hypothyroidism & hyperthyroidism
-occurs when gland is overstimulated; TSH is a trophic hormone & chronic stimulation will cause the thyroid gland to grow larger

Causes of hypothyroidism

-primary failure of thyroid gland
-Hashimotos
-secondary to a deficiency of TRH, TSH, or both
-inadequate dietary supply of iodine

Treatments of hypothyroidism (in a adult)

Reversible w/ thyroid hormone replacement therapy or iodine in diet

Cretinism

-hypothyroidism during perinatal period

Causes of hyperthyroidism

-Graves disease

Treatment of hyperthyroidism

-surgical removal of a portion of the over-secreting thyroid
-administration of radioactive iodine
-use of anti thyroid drugs

The anatomy of the Immune system

Immune cells are made: bone marrow & thymus
Secondary immune sites: tonsil, adenoid, appendix, Peyer's patches in small intestine

Leukocytes (White Blood Cells)

-collective name for all the immune cells in our body
-2 board categories: lymphoid & myeloid

Lymphoid cells consist of

-T lymphocytes
-B lymphocytes
-Natural killer cells

Myeloid cells include

-monocytes/macrophages
-granulocytes & precursors for RBCs & platelets

What is the precursor of all the cells in the immune system?

Hematopoietic stem cell

T lymphocytes (T cells)

-originate in the Thymus
-necessary for cell-mediated immunity
-uses T cell receptors

B lymphocytes (B cells)

-originate in the Bursa of Fabricius (& the Bone Marrow)
-necessary for humoral immunity
-uses B cell receptors =antibodies

humoral immunity

Factors in the humoral phase of the blood; soluble antibodies

Macrophages

-called monocytes in the blood
-professional phagocytic cells
-scavenge our tissues in search of pathogens, dead cells & other debris

Granulocytes

-professional phagocytic cells that release the content of their granula as part of specific immune response
-4 types: neutrophilic, eosinophilic, basophilic, mast cells

Innate cells types

-macrophages & granulocytes
-natural killer cells

Acquired cell types

-T & B lymphocytes

Intro on B cells

-consists of 2 heavy chain & 2 light chains
-linked by disulfide bonds
-constant domain determines antibody properties
-tip of the variable domain provide the antigen binding site

B cells & antigens

-B cells makes only 1 kind of antibody
-each antibody is HIGHLY specific for one particular antigen

How does the B cells generate a near-infinite # of ABs?

-The random combination of a V, D, J segment provides around 12,000 possible unique combinations for the heavy chain
-the same process generates unique light chains, so that combinatorial power yields over 100 million possible antibodies!!

Negative selection

-many B cells makes antibodies that recognize proteins of our own body, so B cell are killed off in the Bone marrow

Colonial expansion

-Taking a single B cell upon activation & basically just divides over several rounds to produce an army of identical B cells
-army "fights" against a pathogen

Primary Antibody response

-in response to first antigen exposure
-takes a few weeks
-moderate concentration of low-medium strength antibodies

Secondary Antibody response

-in response to subsequent antigen exposure
-takes a few days
-high concentration of high-strength antibodies

How do antibodies help fight pathogens?

-aggulination
-activation of complement pathway
-opsonization
-activation of Natural killer cells

Agglutination

Causes antigenic cells to clump together

Activation of the complement pathway

-a cascade of biochemical responses that ends w/ the formation of the Membrane Attack Complex, which kills pathogens
-is triggered by the binding of the surface of that pathogen by an antibody molecule

membrane attack complex (MAC)

A large pore is made in foreign cell antibodies

Opsonization

-coating of the surface of pathogens w/ Abs, initiating phagocytosis

An intro on T cells

-dimer of 2 TCR chains
-tip of the variable domain provides the antigen binding site
-each T cell has a unique TCR, a large T cell repertoire is generated similar to B cells makes antibodies
-2 major subtypes: helper T cells & cytotoxic T cells

Helper T cells

-provide essential "help" to B cells in mounting a humoral immune response

Cytotoxic T cells

-can kill cells via cell-cell contact
-important in the defense against virus-infected cells & cancer

Can T cells recognize "non-self" in the context of "self"?

Yes

"Non-self"

A fragment of a pathogen after degradation in the lysosomes

"Self"

Refers to the Major HistoCompatibility genes (MHC), which encodes a protein dimer on the cell surface that "presents" this small fragments

Cytotoxic T cell and their ability to recognize "Self"

-All cells express MHC class I
-MHC-1 + peptide is recognized by TCRs on cytotoxic T cells, along w/ a CD8 co-receptor

Cytotoxic T cell and their ability to recognize "Self" pt. 2

-If the peptide is "self" presented in the context of "self", nothing happens
-If the peptide is "non-self", (e.g from a virus that has infected the cells) & is presented in the context of "Self", cytotoxic T cells w/ the right TCR to recognize the peptide will kill the infected cell

Helper T cell and their ability to recognize "Self"

-Specific Antigen Presenting Cells express MHC class II
-MHC-II + peptide is recognized by TCRs on helper T cells, along w/ a CD4 co-receptor

Helper T cell and their ability to recognize "Self" pt.2

-if the peptide is "non-self" (e.g from a bacterium that was phagocytosed) presented in the context of "self" by an antigen-presenting cells (APC), this activates the helper T cell
-Activated helper T cells can then provide help in the form of cytokines to B cells that present "non-self" antigen

Cytokines

Soluble signaling molecules released by the helper T cells to promote proliferation (cell division) of those B cells that are activated

What role does Innate immunity play?

-Innate immune cells are really efficient Antigen Presenting Cells; w/out antigen presentation, there will be no acquired immune response
-also very capable of scavenging our bodies for anything damaging & clean up
-provides a much faster, local response (inflammation) to a threat (damage or a pathogen)

How does innate immunity know to respond?

-innate immune cells recognize Pathogen-Associated Molecular Patterns (PAMPs) or Danger Signals
-PAMPS broadly flag to the innate immune system that something is amiss & requires an immune response

Disorders of Innate Immune System

-genetic mutations in the signaling pathway of the PAMPs or Danger Signals lead to defects of the Innate immune system
-over active innate immune responses lead to auto-inflammatory diseases, usually related to the excess strength of signals that promote inflammation

Disorders of the Acquired Immune System

-rare mutations affect the ability to carry out VDJ recombination
-NO BCRs & TCRs can be made, causing the absence of the acquired immune system

Acquired Immune Deficiency Syndrome (AIDS)

-human immunodeficiency virus (HIV) infects & kills CD4+ helpers T cells resulting in lack of B & cytotoxic T activation

Human Male Reproductive System

-includes gonads, reproductive tract, & accessory sex glands
-Role: make & deliver sperm

Female Reproductive Functions

-production of ova
-reception of sperm
-transport of sperm & ovum to common site for union
-giving birth to the baby

Sexual differentiation of mammalian gonads & reproductive tracts

-testes differentiate from "bipotential" gonads if SRY gene from Y chromosome is expressed
-transiently active testes secrete testosterone (keeps Wolffian ducts alive) & Mullerian Hormone (AMH: induces loss of Müllerian ducts)

Sexual differentiation of mammalian gonads & reproductive tracts pt. 2

In female pathway, Wollfian ducts are lost w/out testosterone & Müllerian ducts become oviducts & uterus

In males, which tract stays and which one goes?

-Mullerian ducts degenerate under AMH influence; Wolffian ducts stay

In females, which tract stays and which one goes?

-Wollfian ducts degenerate; Müllerian ducts stay

Male external genitalia formation induced by...

Local conversion of testosterone from fetal testes to dihydrotestosterone (DHT)
-DHT is another androgen, acts through androgen receptor (AR)

Females external genitalia develop..

In absence of DNT

CAIS (complete androgen insensitivity syndrome)

-Wolffian tubes: degenerate for lack of testosterone input
-Müllerian tubes: degenerate under the influence of AMH

5a-reductase deficiency

-Wollfian tubes: develop into epididymis & vas deferens
-Mullerian tubes: degenerate under the influence of AMH

Male Reproductive System: Testes

Perform dual function: -produce sperm w/in seminiferous tubules
-secrete testosterone from Leydig cells

Are cooler or warmer environments essential for spermatogeneis?

Cooler

Summary of Spermatogensis

-Spermatogonia divide by mitosis to form primary spermatocytes
-primary spermatocytes undergo meiosis I to form secondary spermatocytes
-Secondary spermatocytes undergo meiosis II to form spermatids
-Spermatids undergo spermiogenesism transforming into spermatozoa

Epididymis & ductus deferens

-Store & concentrate sperm
-increase sperm motility & fertility prior to ejaculation

What are the secretion glands that release secretions that are mixed in w/ sperm?

-Seminal vesicles
-Prostate gland
-Bulbourethral glands

seminal vesticles

-Supply fructose & prostaglandins
-provide more than half the sperm

Prostate gland

Alkaline fluid that neutralizes acidic vaginal secretions

Bulbourethral glands

Mucus

Hormonal Regulation of Spermatogenesis

-GnRH: secreted from the hypothalamus, stimulates the pituitary gland to release LH & FSH

LH

Stimulates the Leydig cells in the testes to produce testosterone, which is essential for spermatogeneis

FSH

Stimulates the Sertoli cells, which provide nourishment & structural support to developing sperm cells

Negative Feedback Loop & Testosterone

-as testosterone levels rise in the bloodstream, they provide feedback to both hypothalamus & the pituitary gland to reduce the secretion of GnRH & LH

Inhibin

As inhibin secretion rises, it reduces FSH secretion

Female Reproductive Physiology

-Ovaries: primary female reproductive organs
-secrete female sex steroid hormones beginning at puberty; estrogen, progesterone & inhibin
-produce ova

The follicular phase is..

Pre ovulation

The luteal phase is..

Post-ovulation

Hypothalamus & GnRH in females

-the hypothalamus in the brain produces GnRH; it signals the anterior pituitary gland to secrete two primary gonadotropins: FSH & LH

FSH & ovaries

Stimulates the growth & maturation of ovarian follicles

LH & ovaries

Triggers ovulation, the release of a mature egg from the ovary

The ovaries produce the primary sex hormones:

Estrogen & progesterone

Estrogen

Responsible for the development of secondary sexual characteristics & also plays a key role in the menstrual cycle & pregnancy

Menstrual phase

-low levels of estrogen & progesterone
-lining of the uterus (endometrium) sheds, resulting in menstrual bleeding
-FSH is secreted to stimulate the growth of ovarian follicles

Follicular Phase

-As FSH stimulates the ovaries, several follicles begin to develop, they produce estrogen that causes the uterine lining to thicken in preparation for a potential pregnancy
-rising estrogen levels help to further stimulate the growth of the dominant follicle & inhibit the production of FSH

Follicular Phase pt. 2

-inhibin is produced by the developing follicles & provides further negative feedback on FSH

Ovulation

-rising levels of estrogen from the dominant follicle triggers a surge in LH
-triggers ovulation, the release of the mature egg

Ovulation pt.2

-a smaller surge in FSH also occurs around the same time as LH, which assists in the final maturation of the egg

Luteal phase

-after ovulation, the ruptured follicle transforms into the corpus luteum that secretes progesterone & some estrogen
-progesterone prepares the endometrium to receive a fertilized egg; if it doesn't occur, it degenerates, leading in a decrease in progesterone & estrogen levels

Luteal phase pt. 2

Inhibin: as the corpus luteum produces progesterone, inhibin is also secreted, which inhibits FSH production, preventing further follicular development
-if pregnancy doesn't occur, the decline in progesterone & estrogen causes the endometrium to shed

Estrogen functions

-In uterus: growth of endometrium
-Mammary gland growth
-fusion of growth plates, maintenance of bone density

Progesterone functions

-prevents ovulation
-supports early pregnancy
-maintain health of endometrium

How does birth control work?

Mimics the luteal phase with low levels of estrogen/progesterone

What if fertilization occurs?

-oviduct is site of fertilization
-must occur w/in 24 hours after ovulation
-sperm deposited in vagina travel through cervical canal, uterus, & to upper third of oviduct

Fertilization

-When sperm is bound, sperm bursts open & try's to break down zone pellucida to fertilize egg
-when sperm gains entry, the granules "shut" the door so that another sperm cannot fertilize

Early Stages of Development from Fertilization to Implantation

Blastocyst has two sections: inner cell mass; destined to become fetus
Trophoblast: sticks to uterine lining & causes implantation

Implantation of blastocyst & hCG secretion

-implanted embryonic trophoblast cells secrete a peptide hormone-chorionic gonadotropin (hCG)
-structurally similar to LH; maintains the corpus luteum & estradiol/progesterone secretion