BIOL 620 Exam 1

what is smallpox?

the only eradicated disease; involved rashes -- 3/10 infected could die; caused by *Variola* viruses - now in labs

what is variolation?

inoculate with *Variola* virus; early as 900 AD (Chinese culture), mixed dry pustules with paste, rubbed into nick on person to inoculate

who is Edward Jenner?

noticed milkmaids don’t get smallpox as much (would get cowpox instead); inoculated 8 yo boy with cowpox; 2 months later, exposed to smallpox -→ no sickness; NOT father of immunology

who is Cotton Mather?

was involved in Salem Witch Trials; learned variolation from enslaved person, tried to introduce to America (Boston), was rejected due to religion

Who is Louis Pasteur?

heard about Jenner’s work, used attenuated (disabled) pathogens to build immunity against “normal pathogens”; inoculated sheep against anthrax and made sure there was a lot of media attention on it

1885: boy in NY bit my rabid dog → was sent to France, where Pasteur used attenuated rabies pathogens; the boy recovered

coined term vaccination -- comes from cows; father of immunology

COVID and immunology (think-pair-share)

first mRNA vaccine widely used w/ humans; fastest vaccine developed; proof of concept study (elminated bone marrow cells in cancer patients w/o having to do chemo)

what is immunology?

study of cells and tissues that mediate immunity and investigation of genes and proteins underlying their function

what is immunity?

“to be exempt from;” immune system can be activated against foreign pathogens and altered/unaltered “self” cells - the immune system is more than just battling invaders

what is homeostasis?

natural state of balance of all organs and nervous/circulatory systems; when disturbed by trauma, immune system responds to restore balance

what is the simplest level of the immune system? what do more complex immune systems involve?

simplest level: identifying and clearing damaged/dying cells from body

more complex: evolved to counteract assault on body by infectious agents (bacteria, viruses, parasites, fungi)

what are the 4 types of pathogens? give examples of each

virus (rotavirus - gastrointestinal virus), fungus (candida albicans - causes thrush and vaginal yeast infections), parasite (filaria - clogs lymphatic system which leads to elephantitis), bacteria (myobacterium tuberculosis)

what is infection?

attachment and entry of pathogen into host

what are extracellular pathogens?

don’t need to enter cells to reproduce (ie bacteria, most parasites, fungi)

what are intracellular pathogens?

must enter host cell in order to reproduce (subverts host’s endogenous processes) - ex. viruses, some bacteria, a few parasites

what are some pathogens that are on the bring of being eradicated? what would a world look like without pathogens?

measles, polio, chickenpox; a world w/o pathogens might include a vulnerable population, overpopulated, decreased/weaker healthcare system, untrained immune system, ecological issues

what are two mechanisms underlying immune response?

cell-mediated immunity and humoral immunity; both involved in proper immune response (leukocytes → cytokines: signaling molecule)

what is cell-mediated immunity?

depends on action of cells that destroy or remove unwanted material from body; leukocytes → lymphatic system

what is humoral immunity?

depends on soluble molecules in serum of blood that could eliminate foreign entities (antibodies)

what is the difference between innate and adaptive immunity?

innate

* for all responses
* immediate response
* no memory
* uses PRMs (pattern-recognition molecules)

adaptive

* only activated when innate says there’s serious issue at hand
* delayed response
* has memory
* uses antibodies

what are PAMPS and DAMPS?

PAMPs (for cell damage/pathogens) and DAMPs (for cell damage) trigger initial response for innate system

what are the central elements of innate immunity (5)?

barrier defenses (anatomical and physical, like skin/low pH of stomach acid/tears/vaginal lactic acid), complement activation, phagocytosis, pattern recognition, inflammation, target cell lysis

what is complement activation?

central element of innate immunity; complex system of enzymes that circulate blood in inactive state

what is phagocytosis?

central element of innate immunity; sophisticated means of engulfing entities

what cells usually engage in phagocytosis?

PRR (pattern-recognition receptor) cells: neutrophils, macrophages, dendritic cells - usu called phagocytes; involved in antigen presentation

what is pattern recognition?

central element of innate immunity; pattern recognition receptors (PRRs) recognize PAMPs and DAMPs

how is inflammation significant in innate immunity?

once PRRs are engaged, pro-inflammatory ==cytokines== are produced (signaling molecule); localized gathering of cells and molecules necessary to repair tissue damage and clear pathways

how is target cell lysis essential to innate immunity?

cancer cells and cells with intracellular pathogens express PAMPs and DAMPs; target cells are lysed via neutrophils, macrophages, natural killer cells

what are the cells involved in adaptive immunity?

lymphocytes (B and T cells)--responsible for specificity (antigen receptors specific for one pathogen presented on lymphocyte surface), division of labor (helper & cytotoxic T cells vs B cells), memory (immunological memory & clonal selection), diversity (somatic recombination), tolerance (avoid attacking normal self-cells)

what is immunological memory?

enhanced adaptive response mounted upon second and subsequent exposures to given pathogen so that signs of clinical illness are mitigated/prevented

what is clonal selection?

only lymphocytes bearing receptors specific for particular antigen are triggered to respond to stimulus

what is somatic recombination?

shows diversity of adaptive immunity; single, random combo of gene segments is created in each developing lymphocyte (guarantees there will be least one clone expressing unique receptor sequence for every antigen encountered during host’s lifepsan?)

what is central tolerance?

eliminates lymphocytes early in development so they don’t attack self-cells

what is peripheral tolerance?

silences any lymphocyte that escapes central tolerance

what is primary acquired immunodeficiency?

affected individual born with genetic defect that impairs innate/adaptive immune responses

what is secondary acquired immunodeficiency?

external factor (nutritional imbalance, pathogen) may cause loss of innate system component

summarize the immune response in 1-2 words

recognition and response

what is hematopoesis?

generation of all RBCs and WBCs; all come from hematopoetic stem cells (HSCs)

what are the two distinct lineages that arise from HSCs?

myeloid, lymphoid

what is the differentiation of HSC? (that diagram we need to know)

where are HSCs found in infants? how early are HSCs detected after conception?

detected 3-4 weeks after conception (shows they are crucial for development); found in liver, tibia, femur, etc in infants/children

where are HSCs found in adults?

axial skeleton: sternum, ribs, vertebrae, pelvis, skull

what is the myeloid lineage involved in? what types of cells comprise this lineage exclusively?

innate immunity; involves granulocytes (basophils, eosinophils, neutrophils which harbor **intracellular granules**) and monocytes & macrophages (myeloid cells which use means besides granules to carry out functions)

what are neutrophils? (how abundant are they, what is their lifespan, and what are their functions)

most abundant leukocyte, majority of cells in inflammatory response; 1-2 day lifespan, quick-acting (30 minutes after acute injury) using local chemokine gradient

**functions:** phagocytosis (PRRs of neutrophils bind DAMPs or PAMPs), degranulation (attaches to pathogen, releases granules into site)

what are basophils? (why were they named, what is their abundance/location, functions)

named due to dark blue exhibited when stained with hematoxylin; present in **low numbers**, primarily in **blood**; granules contain substances important for sustaining **inflammatory response**

**functions:** degranulation, phagocytosis (rarely)

what are eosinophils? (why were they named, where are they, what do they do)

named due to color; granules filled with highly basic proteins and enzymes effective in killing **large parasites**; in **connective tissues** of body

**function**: degranulation

what are monocytes? (size, functions, features)

some of the largest cells in blood circulation; patrols blood for one day, then enters tissue where they differentiate into macrophages or dendritic cells

**functions**: phagocytosis mainly, secretion of cytokines for inflammation

what are macrophages? (size, location, lifespan, functions)

several times larger than monocytes, in various tissues around body; have specific names depdnding on where they are in body (Kuppfer cells in liver, osteoclasts in bone, littoral cells in spleen, etc); long-lived (2-4 mos), devoted to **phagocytosis** of pathogens/spent cells; **antigen-presenting**: can’t activate naive T cells; **hyperactivated**

**functions**: phagocytosis, cytokine secretion, antigen presentation

what is hyperactivation relative to macrophages?

activated T cells secrete cytokines that give macrophages additional properties

what is the lymphoid lineage involved in?

adaptive immunity

what cells are involved in the lymphoid lineage exclusively?

T & B cells (cluster of differentiation (CD) markers), natural killer cells

* programmed to die unless they bind to antigens -- specific

what is cross reaction?

antigen may be recognized by more than one lymphocyte (B/T cell) if shape and properties are similar

what are dendritic cells? (function, how they develop)

develop via lymphoid or myeloid lineages; samples tissue environment for presence of DAMPs and PAMPs; only cell capable of activating native T cell

functions: secretion of cytokines that induce local inflammatory response, presentation of pMHCs containing non-self peptides to naive T cells under conditions that allow activation

what is lymphocyte priming?

binding of specific antigen activates lymphocyte to proceed through cell division; progeny cells undergo morphological and functional changes that result in **lymphoblasts** 18-24 hours post antigen perception; lymphoblasts differentiate into short-lived effector cells and long-lived memory cells

what is a B cell? (effector, function)

effector is plasma cell which secretes antibodies

what is a Tc cell? (effector, function)

effector cell is cytotoxic T cell (CTL) for target cell cytolysis and cytotoxic cytokine secretion

what is a Th cell? (function)

effector cell secretes copious cytokines supporting B & Tc responses

what are cluster of differentiation (CD) markers?

specific cell surface proteins expressed on different lymphocytes; allows for identifying and distinguishing between B & T cells; sometimes referred to as co-receptors

what are T cells? (lifespan, CD markers associated with subtype)

mature cell carries \~30,000 copies of T cell receptor (TCR); majority are alpha-beta T cells; modest lifespan, CD4 = Th, CD8+ = Tc

**functions**: adaptive immune responses

* CD4+ = cytokine secretion
* CD8+ = cytolysis, cytokine secretion

How many B-cell receptors (BCRs) are on a mature B cell? What is its lifespan? What CD markers are associated with it?

\~150,000 copies of BCRs; modest lifespan (few weeks); CD19+, CD21+

**functions**: adaptive immune responses

* plasma cells secrete antibodies that bind to antigens, marking them for destruction

what are natural killer cells? (size, location, functions)

large leukocytes, in both blood and lymphoid tissues; capable of killing of target cells; not as specific as Tc cells; allow for lysing of cells coated in soluble ab

**functions**: target cell lysis (important for ability to recognize and kill many virus-infected tumor cells)

what are mast cells? (functions)

rare, long-lived cells important for defense against worms and other parasites, key mediators associated with allergy; basic-staining cytoplasmic granules harboring array of pro-inflammatory granules; degranulation of mast cells rapidly triggered by tissue invasion or injury, resulting in flood of cytokines and other molecules that initiate inflammatory response

why is lymphocyte priming efficient in activating adaptive immunity? what would be the consequence of original B or T cell filling role of effector cells?

want appropriate activation; without specialization, would need for original cell to fulfill more roles

how can the innate and adaptive immune system cross over?

* innate immune cells which are able to clear pathogens that are covered in antibodies; these cells express FcR (FC receptors) which bind to Fc region of antibodies
* cytokines secreted by innate immune cells activate and draw various cells associated with the adaptive response
* innate immune cells can also present antigens to cells of the adaptive response
* helping to make sure response is appropriately timed

what is necrosis?

premature death in response to injury to the cell (toxin, trauma); cell swells and bursts; cell debris induces inflammatory response

what is apoptosis?

programmed cell death; occurs naturally; cell components are cleaved and fragmented, and form apoptotic bodies, which are phagocytized by various leukocytes; no inflammatory response

what would be released by necrotic cells but not apoptotic cells? what are the implications of these being released (what happens downstream)?

necrotic cells release DAMPs → innate immunity and neutrophils activated

what leukocyte accounts for the majority of cells circulating in your blood?

neutrophils

which leukocyte resides primarily in connective tissues and is important in destruction of large parasites?

eosinophils

why is it important that leukocytes undergo apoptosis after a specified time patrolling the body?

keeps repertoire of leukocytes fresh, to ensure proper response is mounted when antigen is encountered

T/F: you can distinguish T cells from B cells by presence of CD19 and CD21 on T cells

False

what is lymphoid tissue?

tissue in which lymphocytes are found; range in organization from diffuse arrangements of cells to encapsulated organs; classified as being either primary or secondary in nature

what are lymphoid follicles?

cylindrical clusters of lymphocytes

what are lymphoid patches?

follicles gathering into groups

what are lymphoid organs?

groups of follicles surrounded or encapsulated by supporting tissues and membranes (lymph node)

what is primary lymphoid tissue?

where lymphocytes develop and central tolerance is established; only two types in body, bone marrow and thymus

what is secondary lymphoid tissue?

sites for both antigen accumulation and gathering of leukocytes (primarily APCs and T and B lymphocytes)

what is bone marrow?

primary site of hematopoiesis in adult human (in sternum, some ribs, humerus, ileum, femur)

what is the structure of bone?

outer matrix of bone surrounds central cavity called **medullary cavity**; medullary cavity has honeycomb structure made of thin strands of connective tissue called **trabeculae**; within cavities created by trabeculae lies marrow (red and yellow); circulatory loop is completed from arteries to **venous sinus** which feeds veins leaving bone

what is yellow marrow?

usually haematopoietically inactive, act as energy reserves

what is red marrow?

haematopoietically active

what is the thymus?

lymphoid organ located above heart; location where immature T cells complete their development; important early in life

who discovered the function of the thymus? how?

JFAP Miller, in 1961; performed thymectomies on mice and noticed they succumbed to infection and died prematurely

what is the structure of the thymus?

bi-lobed organ in which each lobe is encapsulated and composed of multiple lobules that are separated from one another by **trabeculae**; as thymocytes mature through various stages, they generally move from densely packed outer cortex of lobule to sparsely populated **inner medulla**; specialized epithelial cells, ==**nurse cells**== form large multicellular complexes that envelop up to 50 maturing thymocytes

what is thymic selection?

process that thymocytes undergo during their proliferation and maturation in thymus which determines the specificities comprising the mature T cell repertoire; includes positive and negative selection; only 1% of all thymocytes survive selection

what is positive thymic selection?

ensures that only thymocytes expressing TCRs with at least some binding affinity for the host’s MHC molecules survive

what is negative thymic selection?

ensures that thymocytes with TCRs that recognize pMHC complexes in which peptide is derived from self antigen are eliminated

what is thymic involution?

thymus starts to regress after puberty

what are MALT and SALT?

secondary lymphoid tissue; stands for mucosa-associated lymphoid tissues (MALT) and skin-associated lymphoid tissues (SALT); first elements of immune response encountered by pathogen that has overwhelmed body’s passive anatomical and physiological barriers; leukocyte subsets that populate MALT and SALT are situated at the most common points of antigen entry, behind mucosae or respiratory, GI, and urogenital tracts and just below the skin

what is mucosa?

epithelial linings of inner luments

what types of cells are found in MALT and SALT?

DCs, macrophages, NK cells and NKT cells as well as T & B cells are positioned in these locations; throughout most of MALT, leukocytes are dispersed in diffuse masses just under layer of epithelial cells that form wall of body tract

(in some cases, slightly more organized collections of cells exist, such as Peyer’s patches of GALT \[gut\]; other cases, cells are organized into discrete structures such as appendix in GALT and tonsils in NALT)

what are Langerhans cells?

specialized DCs in SALT; secrete cytokines to draw other immune cells when under attack

what is the lymphatic system?

part of secondary lymphoid tissue; all cells in body are bathed by nutrient rich interstitial fluid, which is blood plasma that leaks from capillaries into spaces between cells under pressure of circulation; 90% returns to circulation via venules while 10% filters slowly through tissues and enters lymphatic capillaries (lymph); allows microbes, leukocytes and large macromolecules to pass into lymphatic capillaries; valves in capillaries ensure one way flow, capillaries connect into larger lymphatic vessels

what is the structure of the lymphatic system?

lymphatic vessels connect with one of two large lymphatic trunks called **right lymphatic duct** and **thoracic lymphatic duct**; right lymphatic duct drains right upper body (returns lymph to blood circulation via **right subclavian vein**); thoracic lymphatic duct drains entire lower body (returns lymph to blood circulation via **left subclavian vein**); entire network of vessels and ducts that collect and channel lymph and its contents through body is known as **lymphatic system** (connected with circulatory system ensure pathogens will be caught no matter route of entry)

what are lymph nodes?

secondary lymphoid tissue; as lymph flows through lymphatic vessels it passes through lymph nodes; major site of interaction of lymphocytes and antigens during primary adaptive response; bean-shaped encapsulated structures 2 to 10 mm in diameter; contain large numbers of B/T cells, DCs, plasma cells, macrophages

what is the spleen?

part of secondary lymphoid tissue; abdominal organ that traps blood borne pathogens and recycles RBCs; entire blood volume of adult is circulated through spleen 4x/day

what happens to an animal if they don’t have a spleen or lose it?

animals can lead relatively healthy life, but loss does have consequences; overwhelming post-splenectomy infection (OPSI) in children; adults have “fewer” issues

what is leukocyte extravasation?

to exit from blood into tissue under attack, leukocytes carry out migration process called extravasation

what is the process of leukocyte extravasation?

1. tissue suffering from trauma or infection releases chemokines and inflammatory molecules
2. activated endothelial cells upregulate their expression of cellular adhesion molecules called E-selectins
3. leukocyte temporarily tethered to venule wall, but bonds are relatively weak
4. leukocyte “rolls” (“slow rolling”) over several activated endothelial cells → sequential binding increasingly slows leukocyte
5. during tethering and rolling, intracellular signaling activates leukocyte and causes it to display new adhesion and activation molecules


1. includes **integrins** which bind to intercellular adhesion molecules (**ICAMS**) → causes **activated induced arrest** of leukocyte
6. leukocyte beings crawling over endothelial surface, gaining ability (through specific gene expression) to enter tissue in process called **transmigration**

what are E-selectins?

cellular adhesion molecules which can bind to complementary glycoproteins present on surface of leukocyte that happens to be circulating through venule; causes “slow rolling”

what is lymphocyte recirculation?

gets right lymphocyte to right place at right time; only lymphocytes can regularly shuttle back and forth btwn blood and tissues in absence of inflammation (B and T cells and some NK cells)