Biol 216 - Topic 14

infection

condition in which pathogenic microorganisms penetrate host defenses, enter the tissues, and multiply

virus

infectious particles that invade every known type of cell

Obligate intracellular parasites

Multiply by taking control of host cell’s genetic material and regulating the synthesis and assembly of new viruses - ultramicroscopic + unable to generate energy

virion

fully assembled infectious virus - released by infected cells

RNA viruses

comprise 70% of all viruses - much higher mutation rates than DNA viruses

virus structure

protein shell (capsid) surrounding a nucleic acid core (DNA or RNA)

• Possess only the genes needed to invade a host cell and

redirect its activity

enveloped virus

have outer phospholipid/glycoprotein coat - CoV, HIV

naked virus

no envelope - papilloma

complex virus

have extra structures - poxvirus

provirus

the genetic material of a virus that’s incorporated into genome of a host cell via integrase enzyme

HIV

enveloped retrovirus - uses its own reverse transcriptase enzyme to produce DNA from its RNA genome → incorporated into host cell genome via integrase

reverse transcriptase

enzyme that generates complementary DNA from RNA template

viral multiplication steps

adsorption, penetration, uncoated, synthesis - replication + protein production, assembly, release

chickenpox/shingles latency

after recovery from chicken pox → virus enters nervous system - lies dormant for years → reactivates and travels along nerve pathways of skin → shingles

damage of infections

rapid large scale proliferation → shut down of metabolism/genetic expression, destruction of cell membrane/organelles, release of lysosomes, cell death, latency

cytopathic effects of viruses

cells round up and clump, inclusions in cytoplasm, syncytium, etc

syncytium

mass of cytoplasm contains several nuclei + enclosed in membrane - no internal cell boundaries

inclusion

body suspended in the cytoplasm - ex: granule

bacteria

produce toxics → disrupt normal cell function - damaging specific cells, blocking transmission of internal signals, over stimulating cells until malfunction

cholera toxin

bacteria that disrupts ionic balance of cell membranes → small intestine cells secrete lots of water into intestine → diarrhea → dehydration

penicillin

Inhibit formation of bacterial cell wall - block cross-linking of the cell wall structure

tetracyclins

inhibit protein synthesis - bind to subunit of bacterial ribosome

quinolone

block DNA synthesis - inhibit DNA gyrase bacterial enzyme

first line of defense

nonspecific: physical barriers, chemical, genetic

first line of defense examples

Skin: resist pathogen penetration, replication

Mucous membranes: chemical viral inhibitors - prevent attachment to cell, directly inactivate virus

Lysozyme: damage bacterial cell walls; abundant in a number of secretions

Acidic environment of stomach kills many bacteria

Specificity of viruses to a host cell receptors

second line of defense

nonspecific, innate → immune system

third line of defense

specific, adaptive → acquired immune system

innate immune system

acts sooner, responses are broad spectrum, no memory of lasting protective immunity

PAMPs

found on pathogens - ex: LPS on outer membrane of bacteria → activate innate immune system

DAMPs

cell components released during cell damage/death - ex: presence of DNA outside of nucleus/mitochondria → activate innate immune system

PRRs

identify PAMPs and DAMPs, found on particular immune cells - ex: TLRs → activate innate immune system

cytokine

signaling proteins secreted from helper T cells → initiate antibody production + activate T cells - ex: INF, TNF, IL, growth factors, chemokines

pyrogen

polypeptide that produces fever - raises set point of hypothalamic thermostat

purpose of fever

inhibits multiplication of temp sensitive viruses + stimulates phagocytosis

stem cells in bone marrow can become…

WBC: granulocytes, monocytes, lymphocytes

granulocytes

WBC, contain granules in cytoplasm - ex: neutrophiles, eosinophils, mast cells, basophils

monocytes

agranulated phagocyte w/ clear cytoplasm, larger

migrate through blood to infected tissues via chemotaxis + differentiate into macrophages and dendritic cells

lymphocytes

found in lymph, no granules, refer to 3 WBC: NK, T, and B cells

NK cells

lymphocytes that circulate in blood, function mainly in innate immunity - kill cells

T cells

lymphocytes that migrate to thymus - cell mediated, cytotoxic adaptive immunity

B cells

lymphocytes that stay in bone marrow - humoral, antibody-driven adaptive immunity

innate immune response parts

inflammation, phagocytosis, interferon, complement

inflammation

activated by cell/tissue damaged from pathogen → interferes w/ further pathogen replication/multiplication

inflammation effects

vasodilation, redness/warmth, incr circulation, swelling, leakage of vascular fluid, production of chemical mediators for fever/WBC

chemokine

type of cytokine - induces directed chemotaxis in nearby responsive cells → attracts immune cells to infection

inflammation steps

1. break in skin → introduces bacteria

2. activated mast cells → release histamine

3. histamine + cytokine dilate local blood vessels

4. chemokines attract neutrophils → pass between cells of blood vessel wall

5. neutrophils engulfs pathogens → destroy them

histamine

produced by basophils/mast cells - part of immune response → incr permeability of capillaries to WBC - can engage pathogens in infected tissues

phagocytosis

type of endocytosis - cell membrane actively engulfs large particles/cells into vesicles

chemotaxis

cell migration in response to chemical stimulus - leads to endocytosis

phagocytosis steps

chemotaxis, ingestion, phagolysosome formation, destruction, excretion

phagocyte

WBC that engulfs other cells/particles - ex: neutrophils, monocytes, macrophages

interferon (IFN)

glycoprotein produced by fibroblasts/lymphocytes/T cells/macrophages, epithelial cells, not virus-specific, activates NK cells/macrophages, enhances phagocytosis

IFN process

binding of virus to host cell → IFN synthesis → secreted by cell into extracellular space → binds to another host cell → activates protein production + degrade viral RNA/prevent translation of viral proteins

complement

nonspecific group of proteins in blood plasma → forms membrane attack complex - creates holes in membrane to kills cells

involved in both nonspecific and specific immunity

complement cascade

3 pathways: classical - C1 binds complex, lectin - MBL binds foreign surface, alternative - C3

complement protein process

1. bind directly to bacteria surface → activated

2. cascade reactions → production of many complement proteins

3. form membrane attack complexes → create pores in membrane

4. lysis of pathogen → disrupts structure and dies

RNA interference (RNAi)

nonspecific defense to virus, cellular mechanism - destroys viral dsRNA, inhibits virus life cycle

NK cell defense to viruses

activated by interferon → secrete perforin and enzymes to degrade DNA + trigger apoptosis

perforin

secreted by NK cells + cytotoxic t cells → create pores in target cell + rupture infected cells

antibody mediated immunity

adaptive immune response, humoral - plasma cells from B cells secrete antibodies → circulate in blood → bind to antigens → clear antigens from body

cell mediated immunity

adaptive immune response - specific T cells activated → attack and kill foreign pathogens/infected cells

antigen

molecule bound to antigen-specific antibody/receptor → trigger immune reactions

epitope

specific molecular group of antigen → defines its specificity + triggers immune response

gene segments

encode for receptors on surface of T/B cells and regions on antibodies

antigen specificity

gene segments rearrangements → wide assortment of receptors on T/B cells + antibodies → has unique configuration that is reactive to specific antigen

V(D)J recombination

genetic recombination in developing lymphocytes during early stages of T/B cell maturation → highly diverse antibodies and TCRs

clone

gene segment rearrangement → genetically unique line of lymphocytes - each T/B cell clone responsd to 1 specific antigen

thymus

organ in immune system where T lymphocytes mature and train

clonal selection theory

stem cell differentiates/genetic rearrangement → produces immature lymphocytes w/ many different antigen receptors

those that bind to antigens from body’s own tissue → destroyed - rest mature into inactive lymphocytes

those that encounter matching foreign antigen → activated to produce many clones of themselves

hematopoietic stem cell

gives rise to all other blood cells - located in red bone marrow

immunoglobins

large glycoprotein molecules - serve as antibodies + specific receptors of B cells

antibodies/immunoglobin ((G)

WBC secreted by plasma cells - WBC derived from B cells, reside in blood plasma

antibody structure

Y-shaped - constant region for complement binding site, variable region for specific antigen binding sites (from recombination), connected via disulfide bridge

IgM

found in surface of unstimulated B cells/free in circulation

first antibodies secreted by B cells in primary response - stimulates macrophages and complement system when bound to antigen

IgG

found in blood/lymphatic circulation 

mainly in primary and secondary responses - crosses placenta for fetus immunity, activates phagocytosis and complement system

IgA

found in body secretions

blocks attachment of pathogens to mucous membranes + immunity for breastfed infants

IgE

found in skin and tissues lining GI/respiratory tracts, secreted by plasma cells

stimulate mast cells/basophils to release histamine → trigger allergy response

IgD

found on surface of unstimulated B cells

membrane receptor for mature B cells → important fro clonal selection

B vs T receptor structure

both contain antigen-binding sites + embedded in plasma membrane

B cells have Y-shaped Ig

allergies

hypersensitive disorder of immune system - person’s immune system reacts to allergens (normally harmless subst in environ)

allergic reactions

excessive action of certain WB by IgE → dangerous inflammatory responses

antibody diversity process in B cells

genetic rearrangements combined segments into genes encoding light + heavy chains → transcribed into mRNA and translated into antibody polypeptides

B cell differentiation: V and J DNA segments join w/ C → functional light/heavy chain gene - DNA between V and J deleted

dendritic cell

antigen presenting cell - present in tissues in contact w/ external environment

capture pathogens → migrate to lymph nodes - interact w/ T/B cells → initiate adaptive immune response to make antibodies specific to the pathogen

Helper T cells

contain CD4 - trigger both humoral and cell-mediated response → create cytokines, release chemical factors, help B/T cell growth/activation

Helper T cells activation

antigen fragment displayed in APC → bind to T cell receptor on helper T cell

APC

contains MHC class II proteins → present antigens to activate T cells - ex: dendritic cells, macrophages, B cells

helper T cells process

1. antigen-presenting cell engulfs, degrades, and displays antigen fragments w/ class II MHC molecules

2. specific helper T cell binds to complex via CD4 protein

3. APC secretes cytokines → activate helper T cell

4. activated helper T cell clones itself → secrete other cytokines, activate B cells and cytotoxic T cels for humoral immunity + cell mediated immunity

activation of B cells in humoral response

activated helper T cells → activate B cells to make clones + plasma cells → humoral response + antibodies

plasma cells

specialized B cells - secrete antibodies to surrounding tissue

memory B cells

not fully differentiated B cells - contain receptor for particular antigen and react later

B cell activation process

1. helper T cell activated from APC complex

2. B cell w/ same receptors for epitope internalizes antigen → displays fragment w/ class II MHC complex

3. activated helper T cell binds to and activates B cell

4. differentiates into memory B cells + antibody-secreting cells - specific for same antigen that initiated response

antibody activities to antigen

unite w/ and coat virus, immobilize and aggutinate, enhance phagocytotic recognition, prevent attachment of receptor site, rupture virus w/ complement

agglutination

cross-linkage of antibodies → aggregate and immobilize antigens into clump - prevented from infecting cells

antibodies kill invading bacteria by…

agglutination of bacteria, stimulating complement system, enhancing phagocytosis, allowing innate immune response to initiate membrane response complexes

antigen binding in B vs T cells

T cells: antigen receptors bind only to antigens that are displayed

B cells: antigen receptors bind to epitopes of intact antigens on pathogens OR circulating free in body fluids

antibody-mediate immune response process

1. bacteria taken up by phagocytosis → degraded in lysosome

2. antigens displayed on APC cell surface + bound to class II MHC proteins → presented to CD4 T cells w/ TCRs that recognize the antigen

3. activated T cell secretes cytokines → T cell proliferates and clones → differentiate into helper T cells

4. BCR of B cell binds to antigen - bacteria engulfed and degraded

5. antigens produced are displayed again → TCR of helper T cell recognizes specific antigen on B cell

6. helper T cell links B cell and APC together → B cell proliferation and clones

7. cloned B cells differentiate into plasma cells and memory B cells

CD4

expressed on mature helper T cells - co-receptor for TCR + specific for class II MHC protein

CD8

expressed on surface of cytotoxic T cells - co-receptor for TCR + specific for class I MHC protein

thymocytes

immature cels in thymus - express both CD4 and CD8 proteins initialy

MHC

group of genes that encode MHC antigen proteins found on cell membrane - produces two classes and referred to as HLA in humans