Immunosero Mod 3

INNATE/NATURAL IMMUNITY

immunity Protection by natural means: without production of antibodies Present at birth

uses the same defense mechanism regardless of the character of the foreign Ag

Nonspecific

Uniform response

Lacks memory

characteristics of Innate immunity

Cytokines and chemokines

When tissue is damaged, cells release chemical signals that cause blood vessels to widen and become more permeable, This allows immune cells and fluids to flood the area, isolating the infection and initiating the clean up process what are those chemical signals?

ADAPTIVE/ACQUIRED IMMUNITY

Not present at birth. Born with the ability to produce an acquired immunity but response is not immediately available

Specific

Driver response

With memory

Characteristics of adaptive immunity

Leukocytes

Tissue cells

Cells of the innate immune system

Neutrophils

Eosinophils

Basophils

Monocytes

Lymphocytes

Leuokocytes

Phagocytosis

Main function of neutrophils is

Eosinophils

Most important role is regulation of the adaptive immune response through cytokine release.

Basophils

Inducing and maintaining allergic reactions. Regulate some Th cell responses and stimulate B cells to produce IgE.

Monocytes

Do not remain in the circulation for long (30 hours), they migrate to the tissues and become macrophages

Macrophages

Mast cells

Dendritic cells

Tissue cells

Macrophages

Initiating and regulating both innate and adaptive immune responses Innate immune functions include phagocytosis, microbial killing, anti-tumor activity, intracellular parasite eradication, and secretion of cell mediators

Mast cells

Act to increase vascular permeability and increase blood flow to the affected area. Also play role in allergic reactions and functioning as APCs. Function as a major conduit between the innate and adaptive immune systems

Debdritic cells

The most effective APC in the body, as well as the most potent phagocytic cell

(Lymphocytes)

T cells

B cells

Natural Killer cells

Cells of the adaptive immune system

Helper T cells

Cytotoxic T cells

Regulatory T cells

T cells

Helper T cells

• CD4+ receptor; CD3

•Help B cells to make antibody

Cytotoxic T cells

• CD8+ receptor; CD3

•Kill virally infected cells and tumor cells

Regulatory T cells

• CD4+; CD3

•Help to control the actions of other T cells

2:1

CD4+ to CD8+ ratio in peripheral

Innate Lymphoid Cells

Main properties: They have lymphoid morphology, they do not possess antigen-specific receptors, and they do not have myeloid and dendritic cell markers

Not normally found in the blood; they are located in germinal centers in the peripheral lymphoid organs, or they reside in the bone marrow

Natural Killer Cells

Principal type of innate lymphoid cells

NK cells

Ability to kill target cells without prior exposure to them

Do not require the thymus for development but appear to mature in the bone marrow

No surface markers that are unique

but they express a specific combination of antigens used for identification: CD16 and CD56

CD 16 and CD 56

CD markers of NK cells

Primary lymphoid organ

Secondary Lymphoid organ

ORGANS OF THE IMMUNE SYSTEM

Bone marrow

Thymus

Primary lymphoid organ

Bone marrow

Lymphocyte precursors mature and become NK or B cells

B cells were originally found to mature in an organ bursa of Fabricius of birds

Bursa of fabricious birds

B cells were originally found to mature in an organ

Thymus

Maturation of T cells: 3 weeks From: thymic cortex to the medulla

Different surface antigens are expressed as T cells mature

T cells is created to protect the body from foreign invaders

3 weeks

Maturation of T cells:

Thymic cortex to the medulla

Maturation of T cells: 3 weeks From:

Spleen

Lymph nodes

Mucosal Associated Lymphoid Tissues (MALT)

Secondary lymphoid organs

Spleen

Removes old and damaged cells and foreign antigens from the blood

Red pulp and White pulp

2 main types of tissue in the spleen

Red pulp

Rich in macrophages

Destroy RBCs, platelets, and some pathogens

White pulp

Arranged around arterioles in a periarteriolar lymphoid sheath (PALS)

T cells

Naive B cells (Primary follicles)

what can be found on the white pulp of the spleen

Paracortical area

In the lymph node the T cells are found in the?

MALT (Mucosal Associated Lymphoid Tissue)

CALT (Cutaneous-assciated Lymphoid Tissue)

Other secondary lymphoid organs

MALT (Mucosal-associated Lymphoid Tissue)

Found in GI, respiratory, urogenital tracts

They are the main ports of entry for foreign antigens

Numerous macrophages and lymphocytes are localized here

Tonsils

Appendix

Peyer’s Patches

Examples of MALT

Epidermis

T cells

Monocytes, Macrophages, and Dendritic Cells

Examples of CALT

Physical barriers

Biochemical barriers

External defense system

Intact skin

Mucuous membrane

Cilia

Cough reflex and sneezing

Microbiota

Physical barriers

Intact skin

• Epidermis contains layers of epithelial cells coated with keratin-making skin impermeable to most infectious agents

• Shedding-the outer skin layer is renewed every few days to keep it intact

Mucuos secretions

block the adherence of bacteria to epithelial cells

Surfactants

Mucuos secretions contains ___, that binds to organisms to help move pathogens out

Cilia

Propel microorganism out of the body

Cough reflex and sneezing

Help to move pathogens out of the respiratory tract

Microbiota

Competitive exclusion

TEARS AND SALIVA (Lysozomes, IgA)

EARWAX (Cerumen)

URINE

SWEAT (Lactic acid)

SEBUM

COLLECTINS

ACIDITY OF STOMACH

ACIDITY OF VAGINA

BIOCHEMICAL BARRIERS

TEARS AND SALIVA (Lysozomes, IgA)

• Muramidase or N-acetylmuramide glycanhydrolase

• Attacks the cell walls of microorganisms, esp. gram +

EARWAX (Cerumen)

• Entraps foreign microorganisms

URINE

BIOCHEMICAL BARRIER

• Propel microorganism out of the body

SWEAT (Lactic acid)

• Discourages the growth of microorganisms

SEBUM

Oil produced by the skin.

• Maintain the pH of the skin approx. 5.6

COLLECTINS

• Disrupt bacterial lipid membranes or, by aggregating them to enhance phagocytosis

Hydrochloric acid

keeps the digestive tract at a pH as low as 1

5

Lactic acid production keeps vagina at a pH of __

Phagocytic cells

Eosinophils

Basophils

Mast cells

Dendritic cells

NK cells/ Killer cells

CELLULAR COMPONENTS

Phagocytic cells

• Macrophages/Monocytes

• PMNs

Eosinophil

• Most important role is neutralizing basophil and mast cell products and killing certain parasites

Basophil

• Granules contain histamine, heparin, and ECFA (Eosinophil chemotactic factor of anaphylaxis)

Mast cells

• Plays a role in hypersensitivity reactions

Dendritic cells

• Most potent phagocytic cell in the tissue

• Main function: APC

NK cells/ Killer cells

• Potent source of IFN-γ

• Contain perforin and granzymes involved in cellmediated cytotoxicity

COMPLEMENT

ACUTE PHASE REACTANTS (APRs)

CYTOKINES

PROPERDIN

INTERFERON (INF)

BETALYSIN

HUMORAL (FLUID) COMPONENTS

COMPLEMENT

Alternative pathway –major humoral component of natural immunity

ACUTE PHASE REACTANTS (APRs)

Levels change significantly in response to inflammation

CYTOKINES

INF, ILs

PROPERDIN

• Bactericidal/viricidal

• Can activate complement

INTERFERON

• Inhibits intracellular viral replication

BETALYSIN

• Released by platelets during coagulation; for gram + bacteria except streptococci

Macrophages and Dendritic cells

are the 2 most important cells involved in pathogen recognition

Pattern Recognition Receptor’s (PRRs)

Encoded by host’s genomic DNA and act as sensors for extracellular infection

PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs)

PPRs recognize non-self by this substance which can only be found in microorganisms.

Peptidoglycan (gram + bacteria),

Lipopolysaccharide (gram – bacteria),

Zymosan (yeast),

Flagellin in bacteria with flagellae

examples of PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs)

DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPs)

• Molecules released by host cells that have been damaged or are undergoing stress.

DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPs) • Molecules released

signal “danger” to the immune system, initiating inflammatory response even in the absence of an infection

Initiating stimulus

Cytokines release

Hepatic response

Altered protein synthesis

Systemic effects

Acute Phase Reactant’s process in order

C- Reactive Protein (CRP)

Serum Amyloid A (SAA)

Complement

Alpha1 - Antitrypsin (AAT)

Haptoglobin

Fibrinogen

Ceruloplasmin

Acute Phase Reactant;s

C- Reactive Protein (CRP)

Most widely used indicator of acute inflammation (levels rise and then decline so rapidly)

Levels seen in:

Bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis, and after a heart attack

Serum Amyloid A (SAA)

In plasma, ___ has a high affinity for HDL cholesterol and is transported by HDL to the site of infection

Levels seen in:

Increased significantly in bacterial infections than in viral infections. chronic inflammation, atherosclerosis, and cancer

Complement

Major function is opsonization, chemotaxis, and lysis of cells

Levels seen in:

Low: autoimmune disease, infections (severe bacterial), kidney disease High: acute and chronic inflammation, acute phase of infection, certain cancers

Alpha1 - Antitrypsin (AAT)

Counteract the effects of neutrophil (elastase secretion) invasion during an inflammatory response

Levels seen in:

Lung and Liver disease

Haptoglobin

Acts as an antioxidant against oxidative damage mediated by free hemoglobin. Binds irreversibly to free hgb (released by intravascular hemolysis), once bound, the complex is cleared rapidly by macrophages in the liver

Levels seen in:

Two- to tenfold increase seen following inflammation, stress, or tissue necrosis

Fibrinogen

Small portion is cleaved by thrombin to form fibrils that make up a fibrin clot. The clot increase the strength of a wound and stimulate endothelial cell adhesion and proliferation.

Levels seen in:

Increased levels makes blood more viscous and contribute to an increased risk for developing CAD

Ceruloplasmin

Principal copper-transporting protein in human plasma.

Levels seen in:

Decreased/deplete levels in: Wilson’s disease (ARGDmassive increase of copper in the tissues

Calor

Rubor

Tumor

Dolor

Functio Laesa

Cardinal signs of inflammation

Erythema

(Redness) & HEAT

Edema

(Swelling)&PAIN

Neutrophil

In phagocytosis

o 1 st to migrate

o Short lived

o Early infection

Monocytes

In phagocytosis

o 2 nd to migrate

o Long lived

o Late infection

Adherance

Engulfment

Formation of phagosome

Granule contact

Formation of phagolysosome

Digestion of the microorganisms by hydrolytic enzymes

Excretion

Steps in Phagocytosis

Oxygen Dependent Pathway

Oxygen consumption is increase (Oxidative burst)

Occurs within the cell

Hexose monophosphate shunt is used to change

NADP to NADPH NADPH can reduce oxygen in the presence of NADPH oxidase to Superoxide (O2 – )

Addition of H+ ions to O2 – , SD converts superoxide to hydrogen peroxide or the hydroxyl radical

Formation of hypochlorite ions through the action of MPO in presence of chloride ions

Enzyme activation

Creation of superoxide

Formation of H202

Generation of Hypochlorite

Oxygen Dependent Pathway process

Hexose monophosphate shunt

is used to change NADP to NADPH

Superoxide dismutase

converts superoxide to hydrogen peroxide or the hydroxyl radical

Oxygen independent pathway

NADPH oxidase plays a major role. It depolarizes the membrane when fusion with phagosome occurs, allowing H+ and K+ ions to enter the vacuole

This alters the pH, in turn activates proteases

Defensins (released from lysosomal granules) cleave segments of bacterial cell walls without oxygen

Patients with chronic granulomatous disease that have a genetic mutation that causes defect in NADPH oxidase, resulting in an inability to kill bacteria during the process of phagocytosis

Following phagocytosis, macrophages and dendritic cells mature and are able to process peptides from pathogens for presentation of T cells

T cells then interact with B cells to produce antibodies

cells are not able to respond to intact pathogens, phagocytosis is a crucial link between the innate and adaptive immune systems