BIOL216 Exam 4 - Immune System

infection

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

• potential for rapid, large scale proliferation

virus

infectious particles that invade every known type of cell

• must live inside host cells

• usually ultramicroscopic in size (20-450 nm)

• unable to generate energy - NOT LIVING

how do viruses live inside host cells

multiply by taking control of host cell’s genetic material and regulating the synthesis/assembly of new viruses

how are viruses classified

based on shape and size, chemical composition, structure of genome, and mode of replication

virion

fully assembled infectious virus, released by infected cells

RNA virus

70% of all viruses - vary a lot in genome structure

• higher mutation rate than DNA viruses due to error rate of RNA replication enzymes

virus basic structure

protein shell (capsid) surrounding a nucleic acid core

• possesses only the genes needed to invade a host cell and redirect its activity

enveloped virus

has an outer phospholipid/glycoprotein coat

ex: CoVs, HIV

naked virus

no envelope

ex: Papilloma virus

complex virus

has extra structures

ex: poxvirus

HIV

enveloped retrovirus

• single stranded RNA virus that stores its nucleic acid in the form of an mRNA genome

• uses its own reverse transcriptase enzyme to produce DNA from inner RNA genome

• this DNA is then incorporated into host cell genome using integrase enzyme

*now referred to as provirus

reverse transcriptase

enzyme used to generate complementary DNA from an RNA template

adsorption

1st step of RNA virus multiplication

• virus attaches to host cell by specific binding of its spikes to cell receptors

penetration

2nd step of RNA virus multiplication

• virus enters host cell via endocytosis; vesicle uncoats envelope of virus to free viral RNA into host cell cytoplasm

synthesis

3rd step of RNA virus multiplication

• viral genes indicate host cell to synthesize virus components such as RNA, spikes, and capsomers

assembly

4th step of RNA virus multiplication

• viral spike proteins are inserted into cell membrane for viral envelope to form

release

5th step of RNA virus multiplication

• enveloped virus leaves cell via exocytosis carrying away an envelope with spikes

now this virus/virion can go infect another cell

dsDNA multiplication

main differences from RNA: happens in nucleus, uses host cell’s DNA/RNA polymerase rather than its own

• first go to the nucleus to make viral mRNA and then make viral proteins and whatnot

shingles

chickenpox virus lies dormant for years in nervous system and then eventually reactivates and travels along nerve pathways to the skin

potential damage of infection

can…

• shut down metabolism, genetic expression

• destroy cell membrane/organelles

• release lysosomes

• cause cell death

• cause latency

viral damage to cells

cytopathic effects

• diff viruses can cause diff forms of syncytium/inclusion

syncytium

mass of cytoplasm containing several nuclei and enclosed in a membrane but no internal cell boundaries

inclusion

a body suspended in the cytoplasm such as a granule

bacteria

produce toxins that disrupt normal cell function

• often done by damaging specific cells

ex: cholera toxin

how do bacteria damage specific cells

• block transmission of internal signals

• overstimulating cells so they malfunction

cholera toxin

disrupts ionic balance of cells’ membranes, results in cells of small intestine secreting large amount of water into intestine → causes diarrhea → causes dehydration

bacteria treatment

antibiotics

antibiotics

penicillins, tetracyclines, quinolones

penicillins

inhibit formation of bacterial cell wall by blocking cross linking of cell wall structure

• cell wall is needed as protective casing for bacteria

tetracyclines

inhibit protein synthesis by binding to subunit of bacterial ribosome

bacterial ribosome

30S subunit

quinolones

block DNA synthesis by inhibiting DNA gyrase needed by bacteria

DNA gyrase

bacterial enzyme needed for bacterial DNA synthesis

first line of infectious defense

nonspecific physical, chemical, and genetic factors

physical first line of defense

skin, mucous membranes

skin (defense)

resist pathogen penetration/replication

mucous membranes

physical and chemical viral inhibitors, prevent attachment to cell, directly inactivate virus ; chemical properties = antimicrobial

chemical 1st line of defense

lysozyme, acidic environment of stomach

lysozyme

damages bacterial cell walls; abundant in a number of secretions such as tears, saliva, human milk and mucus

acidic environment of stomach

kills many bacteria

genetic 1st line of defense

specificity of viruses to host cell receptors (recognizes the virus)

second line of infection defense

nonspecific, innate immune system

key players of innate immune system

inflammatory response, phagocytosis, complement, interferons, cytokines

third line of defense

specific, adaptive/acquired immune system

key players of adaptive/acquired immune system

antibodies, T cells, B cells, accessory cells, cytokines

innate immune system

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

innate immune system activated by

PAMPs, DAMPs, PRRs

PAMP

pathogen associated molecular patterns

• found on pathogens

  • ex: lipopolysaccharide

lipopolysaccharide

found on outer membrane of bacteria

DAMP

damage associated molecular patterns

• cell components that are released during cell damage or death

  • ex presence of DNA anywhere other than nucleus/mitochondria - triggers TLR9 response

pattern recognition receptors

recognize DAMP and PAMP

• found on certain immune cells like phagocytes

  • ex: toll like receptors (TLR)

TLR

toll like receptor

• interact with their specific PAMP to induce cell signaling pathways that initiate immune response

• usually expressed on sentinel cells that recognize structurally conserved molecules derived from microbes

sentinel cells

macrophages and dendritic cells

cytokine

substance secreted by certain cells of immune system and have effect on other cells

• ex: interferon (IFN), tumor necrosis factor (TNF), interleukin (IL), and growth factors

pyrogen

polypeptide that produces fever by causing metabolic changes in hypothalamus

exogenous pyrogen

produced by infectious agents

endogenous pyrogen

produced by cells in body like macrophage

fever

stimulate phagocytic immune response

• inhibits multiplication of temperature sensitive viruses

white blood cells

stem cells in bone marrow that differentiate into leukocytes, granulocytes, and monocytes

granulocytes

neutrophils, eosinophils, mast cells, and basophils

• granules (that have hella pathogen killing things like enzymes) are present in their cytoplasm

monocytes

clear cytoplasm and large

• migrate to site of infection and differentiate into macrophages and dendritic cells

lymphocytes

T(hymus) cells, B(one marrow) cells, NK cells

• predominantly found in lymph; no granulocytes in cytoplasm

natural killer cells

function mostly in innate immunity but also in adaptive immunity

b cells

humoral, antibody driven adaptive immunity

t cells

cell mediated, cytotoxic adaptive immunity

**well it’s a lot more complex than this unfortunately😂

first step of innate response

inflammation - activated by cell/tissue damage induced by pathogen

• interferes with further pathogen replication

stages of inflammation

vascular changes, swelling (leakage of vascular fluid) , production of chemical mediators

vascular changes (inflammation)

increased circulation, vasodilation, redness/warmth

swelling (leakage of vascular fluid)

pus is formed at site of inflammation

• swelling with pus pushes on and stimulates nerve endings causing pain

production of chemical mediators

• cause fever, stimulate leukocytes that prevent pathogenic spread

  • ex: TNF (chemotaxis, phagocytosis); IFN (inhibits virus replication); IL (activates wbc)

chemokines

type of cytokine that induces directed chemotaxis in nearby responsive cells

histamine

• produced by basophils/mast cells, found in nearby connective tissues

• increases permeability of capillaries to white blood cells and some proteins so they can engage with pathogens in infected tissues

phagocytosis

type of endocytosis

• chemotaxis → ingestion → phagolysosome formation → destruction → excretion

phagocyte

wbc that engulfs other cells and particles

• neutrophils, monocytes, macrophages

neutrophils

phagocyte: also granulocyte, short lived

monocyte

phagocyte: large,agranulated

macrophages

differentiate from monocytes

monocytes

attracted to damage site through chemotaxis triggered by stimuli like damaged cells, pathogens, and cytokines released by other macrophages

interferon

(group of…?) glycoproteins produced mainly by fibroblasts, leukocytes, macrophages, epithelial cells, T cells; not specific

• activates NK cells, macrophages, enhances phagocytosis

• degrades viral RNA or translation of viral proteins

complement

nonspecific proteins found in blood plasma

• forms membrane attack complex and kills cells by making holes in the membrane

• both nonspecific and specific

• has 3 diff ways to be activated (cascade rxns which allow for complex formation)

RNA interference

nonspecific defense; cellular mechanism, destroys viral dsRNA, inhibits life cycle of virus

NK cells

nonspecific defense (lymphocyte); can be activated by IFN

• secretes perforin and enzymes

perforin

creates pores in target cell, ruptures infected cells

enzymes secreted by NK cells

degrade DNA, trigger apoptosis

apoptosis

programmed cell death

adaptive acquired immune response key players

antigens, immunoglobulins, lymphocytes (b and t)

two types of adaptive immune response

antibody mediated and cell mediated immunity

antibody mediated immunity

(humoral) plasma cells secrete antibodies that circulate in the blood, bind to antigens, and clear antigens from the body

cell mediated immunity

specific T cells are activated that attack and kill foreign pathogens and infected cells

humoral immunity

immune response that occurs in body fluids

plasma cells involved in antibody mediated immunity are derived from…

b cells

antigen

a molecule/structure that an antigen specific antibody or antigen receptor can bind to, and can trigger immune reactions

• can be present in places like the surface of a pathogen

epitope

the precise molecular group of an antigen that defines its specificity and triggers an immune response

self antigen

originates within the body

non-self antigen

originates from external environment

negative selection of T cells in the thymus

t cells get tested in the thymus and if they are found to react strongly to your own proteins they get destroyed - prevents autoimmune diseases

antigen specificity

created by gene segments on surface of T and B cells, and variable region of antibodies

gene segments

encode for receptors on T/B cell surfaces & antibody variable regions

• rearranged extensively to create a huge variety of unique T/B cell and antibody receptors

lymphocyte unique configuration

each T and B cell lymphocyte has a protein receptor with unique configuration; each are specific/reactive a specific antigen

V(D)J recombination

unique mechanism of genetic recombination that occurs in developing lymphocytes during early stages of T and B cell maturation

• is what results in the diverse library of antibodies/immunoglobulins and T cell receptors found on B/T cells