BIO 4226 Part 1

What disease is caused by infection with Variola Virus?

Smallpox

What is vaccination?

inoculation of healthy individuals with weakened or attenuated strains of disease-causing agent in order to provide protection from disease.

What did Edward Jenner use to protect someone from smallpox?

Inoculation with cowpox, a relatively mild disease, which he called “vaccination”

When was smallpox officially eradicated? How?

Around 1980, due to vaccinations

What is the most effective means of controlling infectious diseases?

vaccination

Who proved that infectious diseases are caused by specific microorganisms.

Robert Koch

Who developed vaccine against cholera in chickens and a rabies vaccine.

Louis Pasteur

Who discovered the presence of antibody?

Emil von Behring and Shibasaburo Kitasato

Who discovered the complement?

Jules Bordet

Who discovered phagocytic cells called macrophages?

Elie Metchnikoff

Describe the two kinds of adaptive immunity

Cellular Immune Response: T cells and B cells.

Humoral Immune Response: Antibody from B cells.

Immune activity depends on what cells? Where do they arise?

White blood cells aka leukocytes.

They arise in the bone marrow and circulate in the bloodstream and in the lymphatic system.

Blood cells derive from what part of the bone marrow?

hematopoietic stem cells (HSCs)

List the relative amounts of the following in the body: neutrophils, lymphocytes, monocytes, eosinophils, basophils.

3 main categories of leukocytes and description

• Lymphocytes: T cells and B cells

• Phagocytes: engulf foreign particles. Monocytes, neutrophils, and eosinophils are the main phagocytic cells

• Auxiliary cells: secrete inflammatory mediators which attract leukocytes to the point of infection. Basophils.

What microbes are not pathogens

Commensal microbiome in the gastrointestinal tract, oral mucosa, skin and conjunctiva.

Granulocytes include what cells

neutrophils, eosinophils, and basophils

Three types of phagocytes in the immune system are:

Macrophages, Dendritic cells, Granulocytes.

Describe what macrophages are/do:

• engulf and kill invading pathogens

• general scavenger cell in the body to clear out dead cell and cell debris.

Describe granulocytes. Granulocytes are also called what, and why?

Aka polymorphonuclear leukocytes bc oddly shaped nuclei.

• Have many granules in the cytoplasm

• survive a few days

• mature in the bone marrow

• increase during inflammation and migrate to inflammatory sites

Describe neutrophils

• most numerous and important cells in innate immune response

• phagocytic

• neutropenia (low # of neutrophils) → overwhelming bacterial infection

Describe eosinophils and basophils

• less abundant than neutrophils

• important in defense against parasites which are too large to be ingested by macrophages or neutrophils

• contribute to allergic inflammatory reactions

Describe mast cells

• Begin development in the bone marrow, then mature in peripheral tissues, skin, intestines, and airway mucosa.

• Protecting the internal surfaces from pathogens including parasitic worms.

Describe dendritic cells (DCs)

• discovered by Ralph Steinman in 1970s

• phagocytic

• dendrites of cell membrane

• macrophinocytosis: ingests extracellular fluid

• protecting the internal surfaces from pathogens including parasitic worms

• professional antigen presenting cell (APC)

• immature DCs from the bone marrow and migrate to the tissues

What do sensor cells express to provide an initial discrimination between self and nonself

pattern recognition receptors (PRR)

Infection triggers an inflammatory responses by releasing what?

cytokines and chemokines

Describe how bacteria triggers inflammation pathway

1. sensor cells encounter pathogenic microorganisms recognized by PRRs that produce cytokines and chemokines

2. cytokine affects neighbor cells

3. chemokines and cytokines act as chemoattractant to attract cells bearing chemokine receptors, such as neutrophils, from the bloodstream to an infected tissue → inflammation

Describe natural killer (NK) cells

• do not have antigen-specific receptors

• important to innate immunity

Describe adaptive immunity

• Mediated by antigen-specific lymphocytes which express huge repertoire of receptors that are highly diverse in their antigen-binding sites

• generates immunological memory

Effector means what in immunology?

killing

Describe B cells and T cells

• the two types of lymphocytes

• express antigen receptors

• inactive (naive) until their specific receptor encounters specific antigen

• when activated, they differentiate further to be full, functional lymphocytes

when lymphocytes are activated, they become functional and now called

effector lymphocytes

after antigen binds to b cell receptor (BCR),

B cell proliferates and differentiates into plasma cells which produce antibodies

after antigen binds to t cell receptor (TCR),

T cell proliferates and differentiate into effector T lymphocytes

difference between cytotoxic T cell, helper T cell, and regulatory T cell

cytotoxic: kill cells infected with pathogens

helper: provide signaling or specific cytokines to activate function of other cells like B cells

regulatory: suppress activity of other T cells and limit over-activation of lymphocytes

what do antibodies consist of (chains, regions)?

two identical heavy chains, two identical light chains

constant region/Fc region & two variable regions

A small portion of the antigen’s molecular structure

and the part recognized is called an antigen

determinant or what?

epitope

What do T cell receptors bind?

A complex of an antigen fragment and a self molecule.

How are TCRs unlike most antibodies?

TCR bind a peptide epitope from a partially degraded epitope only it’s buried in the MHC

Where do lymphocytes mature then congregate?

mature in bone marrow or thymus and congregate in lymphoid tissues

What are the central lymphoid organs?

Bone marrow and thymus

What are the peripheral (secondary) lymphoid organs?

lymph nodes

spleen

mucosal lymphoid tissue in the gut, nasal and respiratory tract, and urogenital tract

what are lymph nodes interconnected by, which drain extracellular fluid form tissues?

lymphatic vessels

B and T lymphocytes originate in the bone marrow. Where do B cells complete their development?

in the bone marrow

B and T lymphocytes originate in the bone marrow. Where do immature T lymphocytes complete their development?

the thymus

where do mature naive lymphocytes go

peripheral lymphoid tissues

what do dendritic cells do? what are they also called?

present peptide antigens on MHC molecules of the DCs; antigen presenting cell (APC)

other than DCs, what other cells can act as antigen presenting cells (APC)

B cells and macrophages

What traps antigen-bearing DCs and facilitates initiation of adaptive immune responses?

peripheral immune responses

pathogenic antigens are carried from sites of infection by what?

DCs

Antigen and lymphocytes encounter each other where?

peripheral lymphoid organs

What happens when an infection occurs in tissue?

• free antigen-DCs travel from infection site to peripheral lymph nodes through afferent lymphatic vessels

• then ag-specific lymphocytes activate, and undergo proliferation and differentiation

• they leave as effector cells via the efferent lymphatic vessel

• the effector cells go to tissues through bloodstream (4-6 days) to act.

what is the organization of lymph nodes

follicles: B lymphocytes localized here, make up outer cortex

para-cortical area: T lymphocytes

deep cortex: T cell zones

germinal centers: activated B cells undergo proliferation and differentiation into plasma cells

Tell me about the spleen

• Has no direct connection with lymphatic cells, only blood vessels connected

• Collects antigen from the blood, filters blood-borne pathogens to induce immune responses

• Collects and disposes of senescent RBCs in red pulp

What does MALT stand for? examples?

Mucosa-associated lymphoid tissues.

ex: Gut-associated lymphoid tissues (GALT)

Tonsils

Adenoids

Appendix

Peyer’s patches

Nasal-associated lymphoid tissues (NALT)

Bronchus-associated lymphoid tissues (BALT)

What are Peyer’s patches?

• specialized lymph structure in the small intestine

• Ag collected by specialized epithelial cells called microfold or M cells

• Follicle consists of large dome of B lymphocytes surrounded by smaller number of T lymphocytes

How do lymphocytes enter and leave Peyer’s patches

enter from blood and leave through efferent lymphatics

Lymphocytes activated by antigen proliferate in the peripheral lymphoid organs, generating what?

effector cells and immunological memory

Activated innate and adaptive immune cells employ effector mechanism in order to what?

kill pathogen

What is effector module-1?

Innate immune response

What does effector module-1 include?

NK cells

ILCs (innate lymphoid cells)

What is the function of NK cells and ILCs

• similarities to T cells

• exhibit the cytotoxic capacity of T cells

• produce IFN-gamma to kill Ag

What is effector module-2

antibody protection against extracellular pathogens and their toxic products (humoral immunity)

how do antibodies function

neutralization, opsonization, complement activation

what is effector module-3

cell-mediated immune response (cellular immune response)

how does effector module-3 work

if some pathogens replicate inside cells, cannot be detected by antibodies, so cell-mediated immune responses destroy intracellular invaders, while T cells respond to extracellular pathogens

MHC class I and MHC class II are associated with what T cells

MHC Class I: CD8+

MHC Class II: CD4+

1 × 8 = 8

2 × 4 = 8

MHC class I molecules present what

antigen derived from protein in the cytosol.

CD4+ cells from MHC class II are called what?

Helper T cell

CD8+ cells from MHC Class I are called what?

Cytotoxic T cell

Inherited and acquired defects in immune system results in what?

increased susceptibility to infection

Mosquito bites transmit what disease? How does the bite function?

Malaria

Mosquitos inject saliva to keep the blood from clotting

When mosquitos bite a malaria-infected person, what happens?

They ingest Plasmodium parasites which invade mosquito cells and replicate, then migrate to salivary glands where mosquitos can infect another human in next bite.

It is almost impossible for mosquitos to pass along what disease? why?

HIV; the HIV viruses get digested and die in the insect.

What are ILCs?

innate lymphoid cells: group of innate immune cells that lack B or T cell receptors so don’t respond in anti-gen specific manner