Organs of the immune system

-Bone Marrow

-Thymus

Organs of the immune system

-Lymph Nodes

-Peyer's Patches

-Spleen

Organs of the immune system

-Lymphatic Vessels

-Blood Vessels

A Skin

B Neurons

C Blood

D Liver

Pluripotent depends on signal, growth under diff. conditions:

A.

B.

C.

D.

____---->differentiate----> Only specialized types of blood cells; -red blood cells

-white blood cells

-platelets

Mechanism that ensures that continous and regulated replacement of blood cells

-generated in bone marrow

-transient program

-begins in early embryogenesis (first 8 weeks)

-what we see in adults

-begins during fetal life (placenta)

-expands in the fetal liver and spleen

-establishes in the bone marrow in the late fetus and remains at this site for life

____are multipotent stem cells that give rise to all cells of the immune system

-found in the bone marrow of adults (femurs, hips, ribs, sternum)

- Self Renewal

- Potency

- Exist in small numbers

- Relies on cell surface markers for identification

Same as stem cells because have capacity to differentiate into a specific type of cell

Different then stem cells because pushed to differentiate into their "target" cell and are in the "center" between stem cells and fully differentiated cell

T Cells

B Cells

NK Cells

-Dendritic Cells

-Monocytes/Macrophages

-Granulocytes (neutrophils, eosinophils, and basophils)

-Mast Cells

T Cell

B Cell

NK Cell

Immature Dendritic Cell

Macrophage

Granulocytes (neutrophils, basophils, eosinophil, mast cell, monocytes)

- Distinguishes between self and non-self and protects us from our hostile environment

-Detects and eliminates w/ great selectivity a large variety of immune challenges

-Memorizes previous challenges and increases defense to pathogens- function (goal of vaccine)

-non-specific

-occurs w/in hours

-recognition of motif patterns

-limited # of specialties

-Specific

-Develops after days

-Recognition of structural details

-Large # of specificities 

-Referes to the basic resistance to infection that an individual possesses by virtue of his/her birth

(potential pathogens are encountered routinely, but rarely cause disease. the vast majority of microorganisms are destroyed within minutes or hours by innate defenses)

1. Temp- normal body temp. inhibits the growht of some pathogens

2. Fever- inhibits growth of pathogens by elevating body's temp

3. pH- Acidity of stomach content kills most ingested microorganisms (gastric juice)

-both skin and mucous membranes are protected by variety of antimibrobial substances including:

1. Lysozyme- degrade peptidoglycans of bacterial cell wall

-tears mucous secretions

2. Lactoferm- sequesters iron from microorganisms

-saliva, phagoctyes, blood and tissue fluids

3. Defensins- damage cell membrane of microbes

-mucous membranes (skin, small intestines, and respiratory tract)

-Populationof microorganisms found on the body surface of healthy indivduals is called microbiota- healthy bacteria

-Friendly microorganisms protect through Competivite Exclusion (space and nutrients)

Attracts Phagocytes

-Tissue damage, caused by a wound or by an invading pathogen microorganism, induces a complex sequence of events, known as inflammatory response

3 major events of inflammatory response are:

1. Vasodilation- (red) due to chemical release

2. Increase in capillary permeability

3. Influx of phagocytes from the blood into the tissues

(redness comes due to eradication-as a defense)

Which cells are components of innate immune defense?

  A. NK cells

  B. Dendritic cells

  C. Macrophages

  D. Granulocytes

How soon after infection is the innate immune response triggered?

-attack unhealthy cells (infected)

-Large granular lymphocytes

-specialized in killing

-develop in the bone marrow

- dervie from CLP and HSC

-major surface markers are NK1.1 and NKp46

-found in spleen, blood, liver, lymph nodes

-exist in small numbers in lymphoid organs

1. Recognition of infected cells

2. Release of perforins and granzymes

3. Induction of cell death "apoptosis"

-cells with several denrites

- specialized in ANTIGEN PRESENTATION

-develop in the bone marrow

- derive from CMP and HSC

-major surface markers are CD11c & MHC class II

-exist in small numbers in lymphoid organs

-Big Eaters

-special in Phagocytosis

-develop in the bone marrow

-dervie from HSC-CMP-GMP-monocytes

-major surface markers are CD11b & MHC Class II

-exist in small number in lymphoid organs

-can present Antigen presentation 

-mainly in lymph nodes

1. in the liver

2. in the lungs

3. in connective tissues

4. in the bones

5. in the kidney

6. in the brain

mononuclear cells: macrophages are dispersed throughout the body and are named according to their tissue location:

1. Kupffer cells-?

2. Alveolar Macrophages- ?

3. Histiocytes- ?

4. Osteoclasts- ?

5. Messanglal cells- ?

6. Macroglial cells- ?

Major function: to engulf and digest cellular debris and pathogens= phagocytosis

-processing and presentation of antigens to T-Lymphoctyes

-characterized by presence of granules in cytoplasm

-called Polymorphonuclear Leukocytes (PMN or PML)= nuclear lobed into three segments

3. derived from HSC-CMP-GMP

4. 3 types: Neutrophils, Eosinophils, Basophils

Neutrophils: -Predominant in acute inflammation

- 50-70% of circulating whitle blood cells

Eosinophils: -Associated with allergic inflammation and parasitic infection

- found predominantly in tissues rather than bloodstream

Basophils: -Associated with anaphylactic allergy

-found in blood or in tissues (as Mast Cells)

What are Neutrophils?

What are Eosinophils?

What are Basophils?

Macrophages=Granulation

What is Granulation?

1. Bind to a specific cell-surface receptor & then signaling takes place, which alters cell functions:

-increasing the # of surface receptors for other molecules

- suppressing their own effect by feedback inhibition

- results in production of other cytokines

2. cytokines can share similar functions: Redundant

3. Are pleiotopic- diff. cell types to secrete the same cytokine or for single cytokine to act on several diff. cell types

4. act synergistically (two or more cytokines acting together) or anagonistically (causing opposing activities)

Autocrine- if the cytokine acts on the cell that secretes it

Paracrine- if the cytokine acts on closed neighbor cell

Endocrine- if the cytokine diffuses to distant regions of the body (carried by blood)

Cytokine Action

What is Autocrine?

What is Paracrine?

What is Endocrine?

Pathogen Associated Molecular Pattern

Pattern Recognition Receptor

Ligand is on the pathogen and contians a PAMP. What is PAMP?

Receptor is on the innate cells and contains a PRR. What is PRR?

- Represent the sensor system for pathogens

-Are receptors for PAMPS

-Are mainly expressed in innate cells

-Can be found at the surface or inside the innate cells

B1. Toll-like Receptor (TLR)

B2. Nod Like-Receptor (NLR)

B3. Macrohpage-Mannose Recepor (MMR)

-Membrane Associated receptor

-Expressed on surface

-Expressed inside cell/vacoules

-cyosolic receptors

-Not expressed on the surface

-Expressed inside cell/free in the cytoplasm

-Mannose-rich glycans are short carbohydrate chains with the sugar mannose or fructose as the terminal sugar

-They are commonly found in microbial glycoproteins and glycolipids but are rare in those humans

1: Bacteria binding to MMR

2: Microbe is ingested by

    phagocytosis

3: Phagosome is formed

4: Phagolysosome is formed by

    fusion between phagosome

    and lysosome

5: Enzymes digest the microbe

6: Residual body is formed

7: Discharge of waste material

After phagocytosis, macrophages and dendritic cells can

participate in antigen presentation, in which the phagocyte

moves parts of the ingested material back to its surface

 Phagocytes can communicate with other cells by  producing cytokines, which do what?

1. Destroy invading pathogens and any toxic molecules they produce

2. Highly specific to the particular pathogen that induced them

3. The innate responses call the adaptive immunce responses into play,and they both work together to  eliminate the pathogens

4. Provide long-lasting protection. A person who recovers from measles, for ex. is protected for life against measles by the adaptive immune system

5. The ability to distinguish forgeign from self is afundamental feature of the adaptive immune system

Which type of granulocytes is most abundant in the blood?

Senses pathogens by recognition of PAMPs

What is the function of Toll-like receptors in the immune response?

Which cells of the immune system are phagocytes?

Cytotoxicity- Kills infected cells

Phagocytosis- Kills pathogens directly

What are the differences between killing by phagocytosis and 

       killing by cytotoxicity?

1. T-cells develop in the bone marrow and migrate to thymus

2. Positive selection- T cells that can interact with MHC

3. Negative Selection- T cells that can interact with MHC with only low avidity(entusiasm)

4. Maturation and seeding in the lymphoid system

5. Binding of pathogenic peptides to MHC leads to high-avidity interactions with the TCR and results in T-cell activiation

1. Exogenous Antigens

MHC II

2. Endogenous Antigens

Foreign antigens that are generated within the cell because of viral or intracellular bacterial infection

MHC I

-All cells express MHC I because if virus infects cell can alert  CD8 T cells to kill infected cell

-MHC II only expressed by innate cells that are able to phagocytose pathogen and present it on MHC II which binds to TCR on CD4 T cells= Helper T cells

- The V region of the TCR a(alpha) and b(beta) regions 

- highly variable from one t-cell clone to the next

-reflecting their role in antigen presentation

-recognize peptide fragments presented with MHC I and MHC II molecules found on APCs or target cells

Co-receptor CD4 and CD8 allows prolonged engagement between the antigen presenting cell and the T cell

T_h- which expresses CD4 glycoproteins on their surfaces

T_c- which expresses CD8 glycoproteins on their surfaces

(therefore, acquired immunity is composed of activated CD4(T_h) and CD8(T_c) cellular responses)

Naive Cells-  are cells that have matured, in the central lymphoid organ, have entered the lymphatic system, but that have yet to encounter their cognate antigen

Effector Cells- are cells that have been activated by their cognate antigen, and are actively involved in eliminating a pathogen

Memory Cells- are long-lived survivors of past infections

In state of Activation for T Lymphocytes,

what are Naive Cells, Effector Cells, and Memory cells?

1. progenitor T Cells leave the bone marrow and enter the thymus

2. After arriving at the thymus, these cells enter the outer cortex and begin to proliferate slowly

3. During 3wks of development in the thymus, the differentiating T-Cells progress through a series of stages marked by the changes in their cell surface phenotype

ONE T cell = SEVERAL copies of same TCR

ONE clone of T cells = ONE specificity for TCR

ONE thymus = LIMITLESS clones of T cells

ONE thymus = LIMITLESS specificity of TCR

ANTIGEN = IMMUNOGEN

  Large foreign molecules that can elicit an immune response 

-Proteins and polysaccharides are more immunogenic than lipids and nucleic acids

-Antigens from individuals of same species are less immunogenic than those from distant species

Immunologically active portion of the antigen 

Immunogenicity-The ability of an antigen

to induce an

Immune Response

Antigenicity-The ability of an antigen

to bind specifically

to an Antibody

Antigens must be degraded into small peptides and bound to protein called MHC proteins

They are specialized for the presentation of intracelluar antigens to the TCR of CD8+ T-Cells

(Endogenous Peptides)

They are specialized for the presentation of extracellular antigens to the TCR of CD4+ T-Cells  

(Exogenous Peptides)

Specialized cells = Antigen Presenting Cells (APC)

All cells express MHC-I but only specialized cells express MHC-II, What are those cells?

1. Present endogenously derived peptides

2. Peptide (antigen) can be either self-derived or derived from viruses

3. Because MHC class I is present on all cells, any cell can interact with T-Cells if infected by a virus

1. Present exogenous antigens

2. Antigen has been phagocytosed and processed, ex. bacteria

3. This is performed by professional antigen-presenting cells. ex. macrophages

-Aspect of immunity that is mediated by secreted antibidoes, produced in the cells of the B lymphocyte lineage (B Cell)

-Involves substances found in the humors or body fluids

-Secreted antibodies bind to antigens on the surfaces of invading microbes (such as viruses or bacteria), which flags them for destruction

IgG

IgA

IgM

IgD

IgE

-a form of antibody where the antibodies are:

-called free antibodies

-secreted into the blood and other fluids

a form of antibody where antibodies are:

-attached to the surface of a B Cell

-called surface immunoglobulin (sIg) or membrane immunoglobuling (mIg)

-sIg is part of the B Cell receptor (BCR) composed of surface-bound IgD or IgM and associated Ig-ab hetero dimers

Paratopes

Epitopes

Antigen Binding Site?

Antigenic Determinants on an antigen?

Antigenic Determinants are in variable regions, and they both have millions of different specificities

Ig- Form is free or surface bound

-No antigen presentation by MHC

-Free Antigens

-No Antigen Processing

TCR- Form is ONLY surface bound

-Antigen presentation by MHC

-Antigen processing required

an Ig that:

-makes up 75% of total serum antibodies

-only antibody that crosses placenta

-responsible for protection of newborns

-provides defense against bacterial toxins

an Ig that:

-is found in mucosa (GI, respiratory, urogenital tracts) and secretions (saliva, tears, nasal fluids, breast milk)

-contribute to protection of newborns

-defends external surface body against attachment of microorganisms

-FOUND IN THE GUT

an Ig that:

-is expressed on the surface of B Cells (BCR) and in secreted form

-first antibody to appear in the serum after exposure to antigen (acute infection)

-mainly found in bloodstream

-presence in the cord blood indicates acute fetal infection (does not cross placenta in a healthy situation)

an Ig that:

-is mostly present on B Cell Surface (BCR)

-present in serum (soluble form) in trace amounts

-needed for B Cell maturation

an Ig that:

-is present in low concentration in serum

-found in respiratory and gastro-intestinal tracks

-involved in parasitic infections, allergic and hypersensitive reactions

Step in antibodies mediated host defense for IgG:

1. Antibodies bind epitopes on the surface of bacteria= COATING bacteria

2. Antibody-coated antigen attach to macrophages= Fc-Rc receptor binding

3. Engulfment of bacteria by phagocytosis

Immobilization & Prevention of Adherence

 (won't let bacteria Adhere)

Step in Antibodies Mediated Host Defense for IgA:

1. Bind on cover surface structure (important in adherence)

2. Bind structure in the flagella to block motility

Toxin Neutralization

(the toxin will damage the cell so IgG will neutralize it)

Step in Antibodies Mediated Host Defense for IgG:

1. Antibodies bind soluble bacterial toxins and block interactions of toxins with target cell

1. Agglutination

2. Precipitation

Step in Antibodies Mediated Host Defense for IgM:

1. antibodies bind surface of microorganisms and form clumps of particles of large size which will be removed by phagocytosis- (functions towards bacteria)

2. antibodies bind soluble toxin and from aggregates of neutralized toxin which will be removed by phagocytosis- (functions toward soluble molecules)1.

ü Derive from HSC – CLP

ü Develop in the bone marrow

ü Major surface markers are Immunoglobulins and MHC class II

ü Found in spleen, lymph nodes, blood

ü Represent 30% of lymph Nodes

                            - immunoglobulin selection of B Cell

Diversity

Diversity of antibodies (and TCR in T cells) 

Transition from membrane-bound Ig

to secreted Ig is Called

“Class Switching

In the respiratory tract you will want to switch to an IgE

- doe NOT require presentation of antigen by MHC but

requires a “help / confirmation” from a T helper cell

B Lymphocytes

Development: Self/Non-Self Seletion

-Ig Diversity

-No MHC restriction

Activation: Recognition of free antigens

Proliferation:

Differentiation: Plasma B Cells

-Class Switching

Memory

T Lymphocytes

Development: Self/Non-Self Seletion

-TCR Diversity

-MHC restriction

Activation: Recognition of MHC-Peptides

Proliferation:

Differentiation: Th & Tc Cells

-No Class Switching

Memory

B VS. T Lymphocytes

Development

Activation

Proliferation

Differentiation

Memory

Specificity

of Innate and Adaptive Immune Response

Specific structural components of pathogens are recognized.

Diversity

of Innate and Adaptive Immune Response

 The total number of foreign molecules recognizable by T and B cells is very large ~ 109 distinct molecular determinants.

Discrimination of self from non-self

of Innate and Adaptive Immune Response

The immune system of normal individuals is able to recognize foreign agents while not reacting to components of “self”

Memory

of Innate and Adaptive Immune Response

 Ability to respond more vigorously and rapidly to repeated exposures of the same microbe.

: Disorder in which cells of the immune system are missing (B and T Cell)

Increased susceptibility to INFECTIONs 

Full Blood Count

Antibodies against surface markers of immune cells (T cells = CD4, CD8, CD3, TCR 

B cells = BCR (IgM, IgD), MHC class II)

                  How is Immunodeficiency is diagnosed?

Genetic Factor= Primary Immunodeficiency Lymphocyte Deficiencies 

Antibody Deficiencies 

Phagocyte Disorders

Innate Immunity Deficiencies

                      SCID = Severe Combined

                            ImmunoDeficiency

                             MHC class II deficiency

                             CD3γ deficiency

                                CD8 deficiency 

External Factor= Acquired Immunodeficiency

                                Chemotherapy

                               Drug treatment 

                               Other diseases

                                      AIDS =

Acquired ImmunoDeficiency

Syndrome

                        What causes Immunodeficiency?

which both T and B cells are absent due to a genetic defect

within one year due to severe recurrent infections

SCID is due to mutations in γc gene leading to lack of T and B cells

HIV infects and destroy CD4+ T cells and as result of killing so many CD4+ T cells Immunity is lost

CD4+T cells are very important in cellular immunity

The failure of an organism to recognize its own constituent   parts as SELF which results in an immune response against its own cells and tissues*** Do REACT to SELF***

Systemic Autoimmunity(effects the nervous system)- Immune system attacks

different organs of the body

-Systemic Lupus Erythematosis

                         -Rheumatoid Arthritis

                         - Systemic Sclerosis Dermatomyositis

Autoantibodies directed against contents of the cell nucleus

Organ-specific Autoimmunity-Immune system affects only one organ or tissue type

-Diabetes mellitus type 1 (Pancreas)

                  -Hashimoto's thyroiditis (Thyroid gland)

                  -Multiple sclerosis (Brain)

                  -Myasthenia gravis (Muscles)

Autoreactive T cells with

a TCR specific to myelin components

- is an autoimmune disease that results in

destruction of insulin-producing beta cells of the pancreas

In Autoreactivity- CD8 recognizes cells represented by B Cells -need a MHC-I  (class I)

In Cytotoxicity- B-cell is dead