Immune cells and Organs

A person is bitten by a brown spider and the Drs. use anti-venom. What is this an example of

Artificial Passive Immunity

Clonal selection theory is used to explain the function of ____

Antibodies or activated B cells

Hematopoiesis

the formation and development of all blood cells (RBC, WBC, and t

hrombocytes: platelets)

highly regulated proess

Function of RBC, WBC, and Thrombocytes

1. Carry O₂

2. Fight infections

3. Release pieces of platelets to help with clotting

Function of Hematopoietic Stem Cells (HSC)

1. Regenerate

2. Differentiate into specialized cells: all blood cells

Differentiate between totipotent, pluripotent, and multipotent.

What kind are HSC

1. totipotent can form differentiate into any type of cell, including the cells of the placenta and embryo, forming a complete organism.

2. pluripotent can form into any cell type of the body (e.g., nerves, muscles, blood) but cannot form extra-embryonic tissues like the placenta

3. Multipotent stem cells that can form specific tissues or cell types of a lineage

4. Multipotent

How were HSC identified

Panning Experiment

Cell surface Markers

cluster of differentiation (CD)

markers are another name for distinctive receptors

what marker do HSCs have

CD34

How do we look for HSCs today

• Instead of just removing mature cells, we positively identify HSCs by their unique marker combinations using fluorescent antibodies.

• Key surface markers in mice (classic example):

  • Lin⁻ (still negative for mature markers)

  • Sca-1⁺

  • c-Kit⁺ (CD117)

• Use flow cytometry or FACS (fluorescence-activated cell sorting) → you can physically isolate the exact cells you want with very high purity.

Why are HSCs treatments needed

restore immune cells to humans without an intact immune system

• immunocompromised people

• after cancer treatment

replace blood cells that have a genetic mutation

• sickle cell

• leukemias

• lymphomas

future goals of HSC transplants

remove stem cells, fix a gene using CRISPR and give back to the same patient

complications of HSC transplants

• GVHD (immune attack by donor cells)

• Graft failure (stem cells don’t engraft)

• Infections (immunosuppression)

• Bleeding/anemia

• Organ toxicity

• Disease relapse

Adrenalleukodystrophy (ALD)

HSC treatments with cerebral de-myleation. more common in boys. myelin gets destroyed

Victoria Gray

first patient ever to be treated with CRISPR for sickle-cell disease.

Explain CRISPR with sickle cell

• Fetal hemoglobin (HbF) does not sickle and inhibits HbS polymerization.

• Therefore, higher HbF levels reduce the severity of SCD symptoms

• More BCL11A activity → less HbF → worse symptoms

• Less BCL11A activity → more HbF → milder symptom

two branches of hematopoiesis

myeloid progenitor cells

lymphoid progenitor cells

Environmental signals induce differentiation and cells become committed to specific lineage

myeloid progenitors become

monocytes

granulocytes

erythrocytes

megakaryocyte (form platelets called thrombocytes

Monocytes

mononuclear leukocytes with kidney-shped or notched nucleus

no visuble granules

2-10% of WBC

found in blood

make cytokines, some phagocytosis, present antigen

what can monocytes differentiate into when going into the tissues

macrophages- phagocytosis (repair/remodel, destroy pathogens), cytokine production, present antigens to T cells

dendritic cells - phagocytosis, after ingesting antigens. they present antigens to naive t lymphocytes for initial activation

macrophages that reside in tissues have unique names

Brain

Lung

Liver

Skin

microglia - neural circuit development

alveolar macrophage - remove pollutants and microbes, clear surfactants

kuppfer cell - scavenge red blood cells, clear particles

langerhans - skin immunity and tolerance

dendritic cells

Inactive VS Active

long protrusions

ultimate APC

Inactive

• monitor the body ad sample environment by phagocytosis, receptor mediated endocytosis, and pinocytosis

Active

• Once Ag is captured, DC matures, they digest the material, stop eating, and move to the lymphoid tissue to present Ag to T cells

what are Granulocytes and which cells fall under this category

Multilobed nucluei and cytoplasmic granules

Neutrophils

Basophils

Mast cells

eosinophils

Neutrophils

Polymorphonuclear leukocytes - 40-75% WBC

release chemical to cause direct harm to pathogens and they phagocytose

• High sign = leukocytosis. A sign of indection. PUS

Basophils

in the blood. may get recruited into tissue, inflammation/allergies <1%

Mast Cells

in epithelial tissue that line the body

a major role in asthma/allergies (bronchostriction)

Eosinophils

Mainly in tissue, anti-parasite activity, asthma/allergies

Granulocytes in neutrophils

Proteases - proteins for tissue remodeling (elastase, collagenease)

Antimicrobial proteins - direct harm to pathogens (defensins, lysozome)

histamine - vasodialation, inflammation

Granulocytes in eosinophils

Cytokines -

• Activate and stimulate immune cells (e.g., T cells, B cells, macrophages) 

• Control inflammation and immune tolerance 

• Coordinate immune responses against pathogens and infections  (IL)

Chemokines - attract leukocytes to specific parts in the body (RANTES, MIP)

Granulocytes in Basophil/mast cell

Lipid mediators - regulation of inflammation (Leukotrienes)

major myeloid effector functions

phagocytosis

degranulation - secretion of antimicrobial compounds

cytokine production

present antigen to T cells

Lymphoid progenitor cells

lymphocytes - main players of adaptive immune response (20-40% of WBC in blood, 99% in lymph)

What do lymphocytes include

B lymphocytes

T lymphocytes

Innate Lymphoid cels (including natural killer cells

Dendritic Cell

CD3

CD4

CD8

CD19

function and where are they found

1. signal transdcution element of T-cell receptor (only in T cells)

2. Adhesion molecule that binds to MHC class II molecules; signal transduction (T_H cell)

3. Adhesion molecule that binds to MHC class I molecules; signal transduction (T_C cell and NK cell)

4. Signal transduction; CD21 receptor (B cell)

B cells do what when activated

Turn into plasma cells and those plasma cells secrete antibodies

T helper cells marker and function

CD4

makes cytokines and activates B cells

Cytoxcic T cells

what marker does it have and what is the function

CD8

kills cells

What activates T cells

Antigen presenting cells (APCs)

what activates B cells

1. contact with antigen ( can be APC)

2. T cell permissin

what are the primary lymphoid organs where all immune cells develop

Thymus and bone marrow

where are HSCs found exactly

in the perivacualr niche of medullary cavity of bone marroq

what do stromal cells do and what do they release

provide support by regulating HSC behavior by releasing chemicals; helps the following:

• endothelial cells

• perivascular cells

• sympathetic nerves

• macrophages

• osteoblast

what is the role of bone marrow

maintain HSCs and regulates the differentiation of HSCs into unique blood cells

what does the thymus do

T cells develop initially develop in the bone marrow but then migrate to the thymus to achieve full maturitiy

what is a thymocyte and where is it found

a cell in the thymus that may eventually mature into a T cell

found in cortex

where are mature T cells found

medulla of the thymus

Name the 3 defects in the thymus that can lead to no T cells and reduced B cells

Nude mouse

• immunodeficient mouse model with a genetic mutation (Foxn1) that leads to a defective thymus, resulting in a severe deficiency of mature T lymphocytes (T cells) but the retention of B cells and natural killer

DiGeorge’s Syndrome

• 22q11.2 deletion syndrome. Immune system problems Due to underdeveloped thymus gland

Thymus function and size decrease with age

secondary lymphoid organs are areas

where lymphocytes wait to encountere antigen, becomw activated, undergo clonal expansion, and differentiate into effector cell

how are primary and secondary lymphoid organs connected

give examples of secondary

• via the blood and lymphatic circulatory systems

• spleen, lymph nodes, MALTS including tonsils and adenoids

lymph node

specializes in trapping antigens from local tissues and bringing immune cells together. store memory cells

spleen functions

• filters blood

• trapping and responding to bood-borne pathogens

• marginal zone - border between red and white pulp in the spleen, rich in macrophages and MZ B cells. It’s specialized for rapid immune responses to blood-borne pathogens, especially encapsulated bacteria

spleen architecture: what is the white and red pulp. what is the marginal zone

white pulp - enriched in B and T cells

red pulp - where RBC are destroyed

marginal zone - separation

cohort study

a group with something in common that is followed over time

lymphatic system definition

vessel containing lymph that connect tissue to secondary lymphoid tissue

order of the lymphatic system

1. cell free plasma leaks from the blood vessels and bathes cells in tissues

2. if foreign antigen gains access to tissue, liquid from the lymph gets drained into lymphatic vessels

3. lymphatic vessels pick up this lymph and bring it to secondary lymphoid tissue to be inspected

4. lymphocytes can interact with the trapped antigen in lymphoid tissue

5. lymph vessels drain lymph back into the blood stream via thoraic duct

what is MALT and give the examples

mucosa-associated lymphoid tissues

• less structurally organized lymphoid tissue found along mucosal sites. cells are more loosely associated

gut-associated lymphoid tissue (GALT)

bronchial/tracheal-associated lymphoid tissue (BALT)

nose-associated lymphoid tissue (NALT)

vulvovaginal-associated lymphoid tissue (VALT)

defense against infection at mucosal and epitheal layers

Gut-associated lymphoid tissue (GALT)

peyer’s patch (illium mucosal lining)

What are M cells

Microfold cells that are special epithealial cells that endocytosize antigen and deliver to immune cells

deliver antigen from the intestinal, respiratory, urinary spaces to lymphoid cells in the gut wall

Skin as a secondary lymphoid organ

various loosely organized and diffuse lymphoid tissue is present

tertiary lymphoid organs

ectopic lymphoid structures that develop in non-lymphoid tissues in response to chornic inflammation or infection

associated with favorable outcomes in cancer and infections

lectin

protein that binds to a carbohydrate

c-type lectin

gets its name beause it usually need calcum present for binding

CLRs

recognized carb components of some microbes

• mycobacteria, fungi, virus, parasites, and allergens

• PAMPS = peptidoglycans, mannans, mannose, glucan, chitin