overview of immune system

weapons of immune system

1. cells that ingest or kill infected or altered cells/tissues

2. soluble proteins that neutralize, immobilize, or kill pathogens

the two arms of the immune system

innate and adaptive immune system act together rot initiate rapid and long-lasting immunity

innate immune system

considered non-specific as it recognizes molecular patterns found on different types of pathogens

adaptive immune system

can acquire specificity and memory against individual pathogens and variants. antigen-dependent

innate vs adaptive immunity pathogen recognition systems

innate: rapid response with hours, fixed, limited number of specific ices, and constant during course of response

adaptive: slow response in days to weeks, variable, numerous highly selective specificities, and improve during course of response

both: common effector mechanism for the destruction of pathogens

pathogens load vs weeks of infection graph for innate/adaptove immune deficiencies

mast cell

comes from common myeloid cell precursor. expulsion of parasites from the body by release of granules containing histamine and other active agents.

eosinophil

comes from granulocytes precursor cell which comes from myeloid cell precursor.

kills anti-body coated parasites through release of toxic granule contents.

basophil

comes from granulocyte precursor cell which comes from common myeloid cell precursor.

controls immune responses to parasites.

immune cell development from stem cells in bone marrow

starts as pluripotent hematopoietic stem cells and follows common myeloid cell precursor pathway or common lymphoid cell precursor.

phagocytosis

ability if cells to engulf whole pathogens

monocyte

comes from common myeloid cell precursor.

circulating precursor of macrophages

neutrophil

comes from granulocyte precursor cell which comes from common myeloid cell precursor.

phagocytosis and killing of microorganisms

macrophage

phagocytosis and killing of microorganisms

macrophage effector mechanisms

1) bacteria binding to macrophage phagocytic receptors induces their engulfment and degradation

2) bacterial components binding to macrophage signalling receptors induces synthesis of inflammatory cytokines

inflammation mechanism

caused by innate immune responses.

1) when surface wound, bacteria infects which activates effector cells to secrete cytokines

2) vasodilation increases permeability of capillary wall. fluid, proteins, and cells leave blood to enter tissue.

3) infected tissue becomes inflamed: redness heat, swelling and pain

inflammation-increased blood flow

vasodilation, vascular permeability, and recruitment of immune cells

mobilization of neutrophils

1) numerous neutrophils are stored in the bone marrow and released on demand to fight infection

2)neutrophils go to infected tissue and kill bacteria . neutrophils dies and are degraded by macrophages

small lymphocytes

b cells make antibodies. T cells help B cells and kill infected cells.

plasma cell

terminally differentiated for of B cell that synthesize and secretes antibodies.

natural killer cell

kills virus-infected cells

comes from common ILC precursor. a lymphoid cell

adaptive immune system-clonal army

1) progenitor cells give rise to numerous lymphocytes of different specificities

2) on infection, lymphocytes with receptors that recognize the pathogen are selected

3) proliferation and differentiation of selected lymphocytes

4) effector cells eliminate pathogen

antigen receptor on T and B cells

lymphocytes circulation

through the blood and lymph.

1) native lymphocytes arrive at lymph nodes in arterial blood.

2) pathogens from infected tissue reach lymph nodes via lymphatics

3) lymphocytes and lymph return to the blood via the lymphatics

4) venous blood returns to the heart

primary lymphoid tissue

thymus and bone marrow

secondary lymphoid tissue

adenoid, tonsil, lymph node, appendix, spleen, peter’s patch in small intestine

dendritic cell

activates T cells to initiate their engulfment adaptive immune response. play crucial role in activating the adaptive immune response.

activation of T cells results in…

1) if T cells migrate from lymphoid organ to siste of infection…(1)CD8 cytotoxic T cells killing infected cells and (2)CD4 helper T cells secretion of cytokines that activate innate immune cells like macrophages, neutrophils, and granulocytes

2) if T cells remain in lymphoid organ…(1)specialized CD4 helper T cells interact with B cells that help to produce better antibodies

antibodies and bacterial toxins

1) bacterial toxins bind to cell with receptor for toxin

2) neutralization via antibodies

3) ingestion and destruction by phagocyte

antibodies and bacteria in extracellular space

opsonization before infection and destruction by phagocyte.

properties of the immune system

1) the immune system is a distributed organ that circulates to all areas of the body

2) high level of redundancy supports complex and interconnected responses to foreign stimuli, which may differ among individuals

3) layers of “nonspecific” and “specific” immunity allow rapid responses to new antigens and memory o furious encounters with antigens

roles of the immune system

1) defense against infection

2) defense against tumors

3) the immune system recognizes and responds to tissue grafts and newly introduced molecules

4) the immune system can injure cells and induce pathologic inflammation

the lymphatic system

immune cells originate and develop in primary (central) lymphoid tissues and then migrate to secondary (peripheral) lymphoid tissues

blood as the surrogate of the immune system

good but imperfect. some tissue-resident cells circulate through the blood at very low frequency

hematopoiesis

all blood cells have limited life spans and need to be regenerated

leukocytes

white blood cells. all immune cells minus erythrocytes and platelets

the lymphocytes

T cells, B cells, NK cells, and ILCs

the granulocytes

neutrophils, eosinophils, basophils

mast cells considered granulocyte but undergoes different mechanism than the rest

other immune cells

monocytes which become macrophages when activated

mast cells which are technically granulocytes

dendritic cells

Natural killer (NK) cells and CD8 T cells commonality

have cytotoxic activity and contribute to the elimination of infected cells and cancer

innate immune responses

epithelial barriers, phagocytes, dendritic cells, complement, and NK cells

adaptive immune response

B lymphocytes and antibodies

T lymphocytes and effector T cells

first line of defense

physical barriers at the skin, gut, lungs and eyes/nose/oral cavity through mechanical, chemical, and microbiological means.

line of defense at skin

mechanical: epithelial cells joined by tight junctions and longitudinal flow of air or fluid

chemical: fatty acids, antimicrobial peptides

microbiological: normal microbiota

line of defense at gut

mechanical: epothelial cells joined by tight junctions, longitudinal flow of air or fluid

chemical: low Ph, antimicrobial enzymes

microbiological: normal microbiota

line of defense at lung

mechanical: epithelial cells joined by tight junctions, movement of mucus by cilia

chemical: pulmonary surfactant, antimicrobial peptides

microbiological: normal microbiota

first line of defense- eyes/nose/oral cavity

mechanical: epithelial cells joined by tight junctions, tears nasal cilia

chemical: antimicrobial enzymes in tears and saliva, antimicrobial peptides

microbiological: normal microbiota

gut commensal bacteria function

1) compete with pathogenic micro robes for nutrients

2) produce antimicrobial peptides

3) modify the environment to prevent colonization by pathogenic microbes

pathogenic microbes and gut tissue + pathway example

overall: toxins produced by pathogenic microbes can damage intestinal cells, allowing microbes to invade gut tissue

pathway(example):

1) numerous commensal bacteria inhabit the colon

2) antibiotic treatments kill many commensal bacteria

3) pathogens take over, producing toxins that damage the mucosa

4) blood cells leak into the gut

key components of innate immunity

1) specificity- for structures shared by classes of microbes (pathogen-associated molecular patterns aka PAMPs) or damaged cells (damage-associated molecular patterns)

receptors- encoded in germline: limited diversity (pattern recognition receptors)

distribution of receptors- nonclonal (identical receptors on all cells of same lineage

discrimination of normal self and nonself- yes: healthy host cells are not recognized or they may express molecules that prevent innate immune reactions

TLR nuclei acid recognition

will activate to main signalling pathways:

1) MyD88 induces NF-kB transcription factor

2) TRIF induces interferon response factor 3 (IRF3)

both transcription factors trigger expression of Type I interferons (a soluble signalling molecule)

TLRs

toll-like receptors will sense/locate microbial products inside and outside human cells

TLRs on cell surface respond to extracellular PAMPS (like TLR4= bacterial LPS)

endosomal TLRs respond to intracellular PAMPs (like TLR3 = viral dsRNA)

soluble factors

support rapid communication between immune cells and tissues

dendritic cells- mechanism of action

1) immature dendritic cells reside on peripheral tissues

2) at the site of infection, will phagocytose ( pattern recognition receptors or pinocytosis) and are induced to migrate via afferent lymphatic vessels to the regional lymph nodes

3) in lymph nodes, they lose phagocytosis ability but gain ability to present antigen to T cells as mature dendritic cells activate naive T cells in lymphoid organs

overall: links innate and adaptive immune system

white pulp (spleen) and Peyer’s patches

serve similar purpose as lymph nodes for blood- and gut-derived antigens

lymphocyte function

generated against pathogen-specific antigens, allowing them to respond to unique agents.

B cells vs T cells

B cells: recognize extracellular antigens and differentiate into plasma cells that secrete a large quantity of one specific antibody that can bind the surface of the pathogen or infected cells

T cells: respond to intracellular antigens present on the surface of infected cells and then kills the infected cell

both: are classes of lymphocytes that mediate adaptive immunity

antigen receptors

B cell antigen receptor (BCR): membrane bound form of an antibody (immunoglobulin) that the B cell will secrete after activation and differentiation. will usuallly bind to native sequences/structures

T cells: recognizes a pathogen derived protein fragment (peptide epitope) presented in complex wth a self molecule (MHC-major histocompatibility complex aka HLA) on surface of cell. binds to processed peptide presented by MHC.

CD

cluster of differentiation

colonial expansion- purpose/how

allows lymphocytes to respond to a pathogen in highly specific manner.

body generates billions of unique B and T cells with random antigen specificities: during development, they are selected to avoid auto reactivity (not for their ability to respond to foreign antigen)

an encounter with forge in antigen results in activation and proliferation of lymphocyte clones that display specificity for that pathogen (clonal expansion)

B cell clonal expansion pathway

1) precursor cells turn into different resting B cells via proliferation and diversification in bone marrow

2) antigen binding to specific B cell in peripheral lymphoid organ will lead to proliferation (clonal expansion) and differentiation of that specific B cell

3) the anti-body secreting effective B cells will secrete antibodies.