1- Elements of the Immune System & Their Roles in Defense

Describe the Immune response and what happens at
each location below (be sure to think about both innate
immune and adaptive immune cells are molecules):
• site of infection
• secondary lymphoid tissues
• blood stream
• lymphatic vessels

The immune response involves the activation of innate and adaptive immune cells and molecules in several key locations. At the site of infection, innate immune cells such as macrophages and neutrophils respond first, detecting pathogens and initiating inflammation. In secondary lymphoid tissues, like lymph nodes, antigen-presenting cells interact with T and B cells, leading to their activation and proliferation. The bloodstream facilitates the transport of immune cells and antibodies throughout the body, while lymphatic vessels help drain interstitial fluid and provide a route for lymphocytes to migrate between tissues.

What happens at the site of infxn?

• cells interact w/ microbe, ID as foreign

• inflammation

  • redness, hot to touch, swelling, loss of function

• wound healing

  • after infection healed

• neutrophils attack infxn

  • kill w/ phagocytosis, can self destruct into net that traps microbes (Neutrophil extracellular trap, throw out net to catch fish)

• macrophages

• B & T cells

  • recognize specific antigens/memory

  • B produces antibodies, evoke adaptive immune response.

  • T kill infected cells/help enhance killing

What do T cells do?

• recognize specific antigens presented by antigen-presenting cells

• can directly kill infected cells

• help activate other immune cells to produce antibodies/enchance killing

What do B & T cells have in common?

both have memory

What are WBCs?

protecting the body against both disease/foreign bodies

• lymphocytes → B cells & T cells

• myeloid cells → neutrophils & macrophages

What are monocytes?

precursor to macrophages & dendritic cells

How do antigens & antibodies interact?

antigen on/of microbe binds to antibodies

What is immunity?

• body’s defense mechanism against foreign antigens

• memory of infxns/microbes seen before

• preventing sickness when exposed to a microbe

  • want to be long lasting, ideally forever

  • acquired by exposure to microbes

    • 1st → acquire immunity

    • 2nd → should have protections

How is immunity obtained?

natural or acquired methods

How is immunity naturally obtained?

• passive → antibodies pass from mother to fetus

• active → infection

How is immunity acquired?

• passive → immune therapy (inject antibodies)

  • keytruda for cancer prevents T cell suppression for targeting tumor cells

• active → vaccines, weakened/part of

What is innate immunity?

• rapid response, ready to go immediately (hours → days)

  • very fast, wants to keep you alive long enough for adaptive

• always FIRST line of defense

• fixed target

  • recognizes general features, non specific

• limited specificities

  • recognizes smaller # of things, type of microbe in gen

• constant in course of response

  • no change over time, helped by T cells

• no memory

What is adaptive immunity?

• very specific to a strain of a specific microbe

• variable → numerous targets

  • B & T cells are highly variable, recognize anything

• slow → days - weeks

• has memory, 2nd infxn = won’t get sick

• always SECOND

• improves over course of response, can adjust specificity

What are the 2 pathogen recognition mechanisms?

innate & adaptive immunity

• cooperate to clear infxn

• common effector mechanisms for destruction of pathogens

What are pathogens?

microbes that make us sick

What is an opportunistic pathogen?

normally harmeless microbe causing disease → microbiota/immune system compromised

What are the classes of pathogens?

• viruses

  • SARS-CoV-2

  • HIV

• bacteria

  • S. pneumoniae

  • S. enterica

  • M. tuberculosis

  • S. auerus

  • L. monocytogenes

• fungi

  • C. albicans

  • P. jiroveccii

  • E. floccum

• parasites (protists & helminths)

  • T. brucei

  • S. mansoni

What makes a productive immune response?

need innate & adaptive immunity working together to clear an infection

Viruses to ID

• West Nile virus

• Yellow fever virus

• Hepatitis A/B virus

• Epstein-Barr virus

• Influenza

• MMR = measles, mumps, rubella

• polio

• V

  • variola

  • HIV

  • Varicella-zoster

  • SARS-CoV/-2

• R

  • rabies

  • rhinoviruses

  • rotavirus

Bacterias to Know

• B (3)

  • bortadella pertussis

  • bacillus anthracis

  • borrellia burgdorferi

  • the anthrax is back in the food, in the bortadella, & burgers

• C (4)

  • Chlamydia trachomatis

  • corynebacterium diptheriae

  • clostriudum tetani

  • vibrio cholerae

  • francisella tularensis

  • haemophilus influenzae

  • coryne hooked up with vibrio in the closet & got chlamydia, francisella was a bad influence

• S (7)

  • Staphylococcus aureus

  • streptococcus pneumonieae

  • streptococcus pyogenes

  • salmonella typhi

  • Schigella flexneri

  • Salmonella enterica serovar

    • S. typhimurium, enteritis

  • salmonella entered the town of serovar & caused typos & typhoid fever

  • strep family is greek, pyogenes & pneumoni

  • please stap flexing

• LMNOP (7)

  • legionella pneumophila

  • l. monocytogenes

  • mycobacterium leprae, tuberculosis

  • mycoplasma pneumoniae

  • neiserria gonorrhoeae/meningitidis

  • yersinia Pestis

  • rickettsia prowazekii

  • treponema pallium

Fungi to know

• Aspergillus

• Trichophyton

• Candida albicans

• Pneumocytis jirovecii

• E. floccum

CAPT = capture/get fungal infection

jirovecci got pneumonia after taking candids in the alberca with its friends tricho & asper who flocced (flaked)

Protozoan parasites to know

• Leishmania major

• Plasmodium falciparum

• Toxoplasma gondii

• Trypanosoma brucei

The Loser Turned Pretty (TLTP)

Major Leish used a plasma gun to shoot down Toxo the Tryp.

Helminth Parasites (worms) to know

• Ascaris lumbricoides (eric asaris’s desk is always alumbrado))

• Schistosoma mansoni (charles manson had schizophrenia)

What happens if there is no innate immunity?

can’t activate adaptive

no adaptive → innate may not save you

What is the microbiota?

good microbes → bacteria, virus, fungi, archaea, protozoa

What are the benefits of the microbiota?

• nutritional benefits → aid in digestion

• barrier to other pathogens & microbes, limiting pathogen replication

• trains immune system → repress responses to new things

• keep pathogens present in check at low levels

What are disruptions to the microbiota?

• broad spectrum antibiotics kill good bacteria

• no good bacteria left to keep pathogens in check

  • pathogens take over & replicate

• pathogens cross epithelium, get into tissue & damage mucosa/epithelial cells

• ex → C. diff (opportunistic)

What is hematopoiesis?

• making blood

• happens in bone marrow, bone marrow transplant replaces all of this

What cells does hematopoiesis make?

• leukocytes → WBC → immune cells

• RBC

• megakaryocytes → platelets

What is a hematopoietic cell?

• stem cell, undifferentiated, eventually lock in

• more diff = more restricted to become something

How does a pluripotent hematopoietic stem cell decide between adaptive & innate immunity?

common myeloid cell precursor or common lymphoid cell precursor

How does a pluripotent hematopoietic stem cell differentiate into innate immune cells?

• common myeloid cell precursor

  • megakaryocyte erythroid precursor cell (non-immune cell

  • granulocyte precursor cell

  • monocyte (in blood)

  • mast cell

How does a common myeloid cell precursor differentiate into non-immune cells?

• megakaryocyte erythroid precursor cell (non-immune cell)

  • erythroblast

    • erythrocyte

  • megakaryocyte

    • platelets

How does a granulocyte precursor cell differentiate?

• granulocyte precursor cell

  • neutrophil

  • eosinophil

  • basophil

GRAN BEN

How does a monocyte differentiate?

• monocyte (in blood)

  • macrophage (tissue, further diff)

  • dendritic cell (tissue, further diff)

How does a pluripotent hematopoietic stem cell differentiate into adaptive immune cells?

• common lymphoid cell precursor

  • common T-cell/ILC precursor

    • B cell

    • common T cell precursor

    • common ILC precursor (innate)

How does a common CD4 T cell precursor differentiate?

• common CD4 T cell precursor

  • diff functions w/in T cells

  • Treg, TH17, TH2, TH1

  • CD8

What is unique about the common ILC precursor?

• common ILC precursor (innate immune cells)

  • NK cell

Erythrocyte

• non immune

• O2 transport

Megakaryocyte

• non-immune

• bleb off/take off PM → form platelets

• wound repair

Which of the following is not a bacteria?

A. Bacillus anthracis

B. Yersinis pestis

C. Treponema pallidum

D. Toxoplasma gondii

D. Toxoplasma gondii

____ immunity is the first line of defense and _________ immunity is the second line of defense

Innate immunity, adaptive immunity

Which of the following is an example of artifical active immunity?

A. Antibodies transferring from mother to child in utero.

B. Recieving immunoglobulin (antibody) therapy after rabies exposure.

C. Vaccination

D. Infection

C. Vaccination

True or False: The microbiota consists of only bacteria.

False, the microbiota includes bacteria, viruses, fungi, and other microorganisms.

During inflammation, what causes the site to be warm to the touch?

vasodilation

During inflammation, what causes the site to swell?

increased local liquid volume

During inflammation, what causes the site to be painful?

pressure on nerve endings

Neutrophils

• 1st responder/quick deploy upon infxn

• kill by → phagocytosis, NETosis

• phagocyte & granulocyte

What is the most abundant leukocyte?

neutrophils, 40-75%

Where are neutrophils found?

bloodstream & bone marrow

• keep reserves in bone marrow

  • self destruct = keep reducing, need backups

What is the structure of neutrophils?

• 1 nucleus, multilobed, minimum 3

• granules inside → content of granule depends on cell type

What is NETosis?

• killing mechanism done by neutrophils, pus = exploded nphil

• release granules into phagosome/cyto

• Neutrophil Extracellular Trap

• granules break out, trap in chromatin, macrophage cleans up

Eosinophils

• granulocytes, small red granules

• 1 nuc → 2 lobes (look like lungs)

• kill antibody-coated parasites w/ releasing toxic granule contents

• mediate allergies

How do eosinophils attack parasites?

granules move to surface, released directly onto parasite & not into our bloodstream

How prevalent are eosinphils?

1-6% of WBCs in blood

• elevated # → parasitic infxn, bad allergies

Basophils

• granulocytes → BIG granules, dark blue/purple

• dumbbell shaped nuclei

• target parasitic infxns → release granules onto surface like eosinophils

What role do basophils play?

• regulatory role in the immune response by releasing granules that target parasitic infections

• no antibody activation required, can be enhanced by antibodies on subsequent infxn

• assist in the activation of other immune cells w/o directly killing pathogens

• DON’T KILL = just help

How prevalent are basophils in the blood?

<1% leukocytes in blood

Mast Cells

• granulocyte → tons of granules

• expel parasites

• granules have histamine → enhance immune response

• round nuc, no lobes

• in tissues

• involved in allergies

What is the function of mast cells?

• granules mediate explusion of parasite → activate peristalsis & coughing (lung contractions)

  • peristalsis → contractions in intestinal lining, push parasite out

Monocytes

• pre-phagocyte

• no phagocytic activity, differentiate into phagocytes

• circulating precursor of macrophage or dendritic cell

• in blood → go into tissues THEN diff

How prevalent are monocytes?

2-10% leukocytes in blood

Macrophages

• 2 JOBS → phagocytosis & inflammation

  • phagocytosis & killing of mo

  • signaling → inflammation & recruitment of immune cells

• in tissue not bloodstream, named for location

  • ex → alveolar macrophage

What is the structure of macrophages?

• divots in 1 side of nunc

• hollow spaces = phagosomes/phagolysosomes

How does phagocytosis by macrophage occur?

1. bacteria interacts w/ receptor on macrophage

2. engulfed by macrophage

3. microbe starts stars being broken down

4. phagosome fuses w/ lysosome

5. contents will be released

How does inflammation by macrophage occur?

1. component of bacteria binds to receptor

2. induces signaling

3. transcription of specific inflammatory cytokines

4. inflammatory cytokines released

   1. diffuse into tissue, enter bloodstream

Dendritic Cell

• phagocyte

• use dendrites to feel for/grab microbes

• phagocytosis of microbes at site of infxn

  • shows pieces of microbe on cell surface receptors

• travel to lymph to activate correct type of T cells & initiate adaptive

Which immune cell bridges the innate & adaptive immune response?

dendritic cell

Small Lymphocyte

• can be B or T cells, main ones in blood & neutrophils

• B cells make antibodies

• T cells help cells (B & more) & kill infected cells

• mainly nuc w/ little cyto

How prevalent are small lymphocytes in the blood?

make up 20-50% leukocytes in blood

Plasma Cell

• antibody factories

• terminally differentiated form of B cell that synthesizes & secretes antibodies

• 1 plasma cell → 1 antibody target → always make 1 type

• BIG ER

• bigger cytoplasm so ER can make more antibodies

Natural Killer Cells

• innate immune cell & lymphocyte

• make tight contact w/ targeted cell, release directly

  • immunological synapse, right on target cell

• have vesicles w/ important mols

• kills virus-infected & tumor cells

What molecules are in natural killer cell vesicles?

• perforin → pokes holes in membranes

• granzymes → induces apoptosis

B/T Cell Receptors

• antigen receptor/binds to antigens (recognize small amino acid w/in proteins)

• each cell have a single antigen specificity

  • all antigen reeptors on 1 cell recognize same thing

    • need diff B/T cells for diff microbes

  • find right one = amplify that clone

• not germ line encoded → diversity from random gene rearrangements

  • not passed on, not heritable, somatic (non germ line)

  • possibilites encoded in germline → B & T cells take them at random & assemble themselves (random gene rearrangements)

• B cells bind directly to antigen, T cells must be shown an antigen by another cell

Antigen

something on microbe that interacts w/ B/T cell, can be part of whole microbe

Major Histocompatability Complex

• shows antigen to T cell (hire bounty hunter)

  • antigen presenting cells have MHCs

  • have to be shown amino acid

• 2 forms → MHC class 1 & 2

  • depends on T cell it interacts w/

MHC Class 1

• present antigens to cytotoxic CD8 T cells

  • toxic #1 mentality

• T receptor binds peptide & MHC class 1

• CD8 coreceptor binds to base of MHC, makes interaction strong

What is an antigen presenting cell

any cell type that’s infected

Antigen vs Epitope

• antigen → whole microbe, specific microbial protein/carb

• epitope → residues that receptors interact w/ T cells only

MHC Class 2

• present antigens to helper CD4 T cells

  • T cell receptors bind peptide & MHC class 2

  • CD4 coreceptor binds the base of MHC

  • professional antigen-presenting cells

What is a professional antigen-presenting cell?

B cell, macrophage, dendritic cell

What are the type of antigens for B cells?

carbs, glycoproteins, proteoglycans, proteins, glycolipids, anything

What are the type of antigens for T cells?

8-16 amino acid peptides presented by MHC mols

• on infected cells or specific cells

• only recognize proteins as short aa sequences

What are the primary lymphatic tissues?

• where B & T cells develop

  • thymus & bone marrow

What are the secondary lymphatic tissues?

• where B & T cells are activated

  • adenoid & tonsil

  • lymph nodes

  • appendix

  • lymphatics

  • spleen

  • Peyer’s patch

Thymus

primary lymphatic tissue, where T cells develop

Bone Marrow

primary lymphatic tissue, where B cells develop & hematopoiesis happens

Adenoid & Tonsil

secondary lymphatic tissue, specialized lymph nodes

Lymph Nodes

secondary lymphatic tissue

• all over the place so if infxn in skin = are nearby

Appendix

secondary lymphatic tissue, some immune functions

Lymphatics

secondary lymphatic tissue, carry lymph between lymphoid tissues, filter fluid back to bloodstream

Spleen

secondary lymphatic tissue, filters blood, immune response to blood infxns

Peyer’s patch

secondary lymphatic tissue, in small intestine

• mucosa-associated lymphoid tissue

• less structurally defined

• functions like lymph node

T/F: blood & lymph circulation have timed intervals.

False, continuous circulation

Why is continuous circulation of blood & lymph important?

B/T cell that’s needed may not be present in affected tissue

What is a lymph node’s structure?

• lymphoid follicle

• T-cell area

• medullary sinus

• afferent & efferent lymphatic vessels

• germinal center

Lymphoid Follicle

where B cells stay (outside)

T Cell Area

where T cells stay

Medullary Sinus

goes all around node, where vessels come in/out

• blood & lymphatic

• arteries & veins have connections in T cell zone

Where do arteries & veins have connections?

in T cell zone