Immunology M1.txt

• 1. Dectecting pathogen invasion
• 2. Initial innate immune response
• 3. Inflammatory response
• 4. Activate the adaptive immune response (T,B cells)

• 1. Commensal: live with us, do not cause disease.
• Enhancehuman nutrition by processing digested food and making several vitamins. Protect us from disease
• 2. Pathogen: Invade or produce toxins, which damage host tissue and cause disease

• Bacteria
• Viruses
• Fungi
• parasites (protozoans and worms)

• Pathogens will invade through all parts of the body where it is open to the outside world.
• Skin: cuts or insect bites
• Gastrointestinal tract: fecal-oral transmission
• Respiratory tract: aerosal transmission
• Urogenital tract: sexual transmission
• Mucosal System: surface lined with mucus secreting epithelial cells in organ systems that open to the environment.

• Extracellular infection: mucosal surfaces tissues interstitial
• Intracellular Infection: cell cytoplasm, endosomal vesicles, or nucleus

• Pathogens:
• a. Viruses
• b. Bacteria
• c. Protozoa
• d. Fungi
• e. Worms
• Protective Immunity
• a. Complement
• b. Phagocytosis
• c. Antibodies

• Pathogen: Bacteria, worms
• Protective immunity: Antimicrobial peptides (defesin), Ab (IgA)

• Pathogens: Viruses, Bacteria, Protozoa
• Protective Immunity: NK cells, Cytotoxic T cells

• Pathogen: Bacteria
• Protective Immunity: T cell and NK cell depedent macrophage activation

• Acute infection
• Chronic Infection

• Pathogen replication strategy
• Host immune response
• Pathogen immune evasion and immune suppression

PAMP (pathogen associated molecular pattern) is the molecule that is specific and common to the pathogen. PAMP will be recognized by a receptor called PRR (pattern recognition receptor).

It is a quick response (innate immune response) and the response evoke is inflammation. The next step is to evoke a more powerful response called adaptive immune response (after pathogen invades) which causes T and B lymphocyte response.

• Anatomical and Physiological Barriers
• Innate Immunity
• Adaptive Immunity

• Block invasion of pathogen - skin
• Removing out (coughing) - cilliary clearance, intestine
• Secreting certain factors - low stomach pH, lysozyme in tears and saliva
• Not only forming a barrier but also prevent attachment, remove, and kill pathogens (secrete antimicrobial mechanism)

You will die quickly cause by infections.

• It is there all the time.
• Quick response.

Eats bacteria, kill virus infected cells, attack protozoan parasites

It helps the effector cells by marking pathogen with molecular flags and also attack pathogens.

Invasion. Cell needs to figure it out (macrophage and DC through their PRR recognizes PAMP). After macrophage recognize they will produce cytokines to produce an inflmmation response. DC goes to the lymph node and give a singal to activate T cells by presenting the Ag. Which starts the adaptive immune response.

Cytokines are P factor that work with cells to trigger an innate response. Cytokines causes the vessels to dilate, increase permeability, and blood flow which causes the skin to warm and redden (inflammation).

When there is a vasodilation there will be gaps between the cells of the endothelium (thin layer of specialized epithelium that lines the interior of blood vessels). This makes the endothelium permeable and increases the leakage of blood plasma into the connective tissue. And lead to edema.

Swelling

• When it recognize specific Ab, B cell will make antibodies and T cell will differientiate different cells (helper, cytotoxic, and regulatory).
• Development of memory immune reponse so that nect time you are infected with the same pathogen the response is faster and more effective.

WBC that helps the innate immune response slow the the spread of infection.

• Surface components
• Nucleic acid
• Metabolic and replication products

• epitope - linear, conformational
• Linear: recognize a stretcher of peptide (1,2,3,4,5, next to each other)
• Conformational: recognize a shape

Recognizes native antigen through cell surface Ig receptor (BCR).

Recognizes processed antigen presented on MHC of Ag presnting cell (APC) by T cell receptor (TCR).

• Antigen (antibody generator) (Ag)
• It is a substance/molecule that when introduced into the body, triggers the production of an Ab byt he immune system.
• Structure: protein or polysaccharide

In normal individual, a primary infection can be cleared by the combined effect of innate immune response and adaptive immune response.

Substance that induces the adaptive immune response (immunogenic)

• Innate: short (hours) to response, humoral effectors are pre-exist but also inducible (defensin, complement, mannose binding lectin, C-reactive protein). Cellular effectors are Phagocytes (macrophage and neutrophils) and Granulocytes (mast cells, eosinophil, basalpil)
• Adaptive Immunity: longer (days-weeks) response time. umoral effectors are inducible (pathogen specific, antibibody), Cellular effectors are Antigen specific T cell (heper - Th), cytotoxic (CTL), and regulatory (Tred).

regulate immune response

kill pathogen infected cells

control immune response

Hematopoietic stem cells int he bone marrow.

• Self renewing and can differientiate to different cells
• 3 common lineage:
• 1. Common Lymphoid progenitor
• 2. Common Myeloid Progenitor
• 3. Common erythroid megatkaryocyte progenitor

Blood cells: oxygen carrying erythocytes and the platele-producing megakaryocytes

• Small non nucleated cell fragments of plate-like shape that maintian the integrity of blood vessels.
• Involve in blood clot to prevent blood loss.

Giant cells with giant nucleus that are made by fusion of multiple precursor cells

• Give rise to the myeloid lineage of cells.
• 1. Granulocytes: have granules that have various anti-microbial, inflammatory functions
• 2. Monoblast: monocytes, macrophages, and DC

because of the unique shapes of their nuclei.

• Phagocytose pathogens and fuse engulfed pathogens with granules that contain many anti-microbial agents to kill the pathogen.
• Circulate in the blood, short lived.

Very little. However when there is a pathogen stimuli they will release their granuli which have E, anti-microbial peptides, blood vessel active agents --> parasitic and allergic reaction.

Circulate in the blood as leukocytes and migrate to the tissue and mature into macrophages or DC.

• Phagocytosis. Long lived
• Scavenger cells of the body, disposing dead cells and cell debris and microorganism and present Ag to lymphocytes.
• Induce inflammation and promote wound healing (by secreting factors).
• First to sense invading microorganism by sensing PAMP with their PRR.

• Sample environment by phagocytosis, macropinocytosis, receptor mediated endocytosis.
• It act as a cellular messengers that sent call up an adpative imune response when needed.
• When it detect an infection it will present Ag to lymphocytes and stimulate adaptive immunity.
• It bridge innate and adaptive immune response

• myeloid cell type
• Live in all connective tissue
• Has granules and contribute to inflammatory.

• Give rise to the lymphoid lineage of WBC.
• 1. Resting lymphocytes: un-stimulated naive lymphocytes in circulation are small with dense nuclei
• 2. Effector cells (activated T cell): fully differentiated lymphocytes that produce Ab (B cells), secrete cytokines to regulate lymphocyte responses (helper/regulatory T cells), or kill infected cells (cytotoxic T cells).
• 3. NK cells

When naive lymphocytes contact with specific Ag, it is acticavated, proliferate and differentiate,

• It is part of the innate immune system
• It is a large granular lymphocyte
• It kills tumor and virus infected cells
• Function without Ag specific activation

• Monocyte, Macrophage
• Neutrophil, Eosinophil, Basophil, and Mast cell

• Least abundant granulocyte
• Very rare, but regulate immune response

T and B lymphocytes

Macrophage and Dendritic cell

• Bring O2 and nutrients to cells
• Remove CO2 amd waste products
• Carries leukocytes (immune cells) to look for infection
• Distribute effector cells to infected tissues

LA - LV - Aorta - Organs and tissues - Veins - RA

RA - RV - Pulmonary arteries - Lung - Pulmonary veins - LA

• They come from bone marrow.
• B cell: mature in bone marrow before entering the circulation.
• T cell: leaves the bone marrow at an immature stage and migrate in the blood to the thymus and mature there.

• Blood flow from arteries - arterioles - capillaries
• Bettwen the arterioles and capillaries the plasma goes into the tissues and become interstitual fluids (carry O2 and nutrients). Only 10-20% goes and become a lymph. 80-90% back to circulation.

Pathogens and pathogen laden dendritic cells from the infected tissue arrive at a lymph node in afferent lymphatic vessels. Exit in the efferent lymphatic vessels.

• It is important so that you have communication between tissue and blood and go back to circulation so the cell can go some place when you have an infection.
• It carries pathogen Ag (also by DC) from tissues to lymph nodes allowing the immune cells, especially of the adpative immune system in lymph nodes to rapidly response to pathogens infections.

• Bone marrow: produce of all leukocytes, B cell development and maturation, and T cell origination.
• Thymus: T cell development

• Lymph nodes: development of adaptive immune response against pathogens in peripheral tissues.
• Spleen: development of adaptive immune response against pathogens in blood circulation.
• Muscosal immune system: development of adaptive immune response against pathogen in mucosal tissues.

B cell segregrate in follicles of the lymph node and form germinal centers when activated.

Paracortical area

Medullary cords

They enter enter the draining lymph nodes through the afferent lymphatic vessel.

Efferent lymphatic vessel

High enthothelial venules (HEV) in the paracorticoid region of lymph nodes.

The process where lymphocytes enters the lymph node.

• T cell enters the HEV in the lymph node.
• TCR CCR7 binds to chemokines CCL21 and CCL19 and get guided through the chemokine gradient.
• Once it binds it allows the interections of various complementary adhesion molecules.
• L-selectin (lymphocytes) bind to GlyCAM-1 and CD34 allows rolling interaction.
• LFA-1 (lymphocyte) is activated by chemokines bound to extracellular matrix.
• Activated LFA-1 is activated it bind tightly to ICAM-1 (endothelium)
• Diapedesis occurs

The spleen will help out! :]

• It is the secondary lymphoid tissue for blood borne pathogen.
• Remove old and damaged RBC.
• Filter blood for pathogen or antigen.
• Initiate immune response to blood borne pathogen.

• Red pulp: RBC area
• White pulp: lymphocytes area organized aroudn the central arterioles
• Lymphocyte follicle: B cells area with germinal center.
• Periarteriolar lymphoid sheath (PALS): T cell rich area.
• Marginal zone: area around lymphocute follicle containing macrophage, DC, and MZ B cells.
• Perifollicular zone: area between MZ and red pulp, blood cells enter spleen.

Blood - lymphocutes - trabecular artery - central arteriole - perifollicular zone

• Blood borne antigen get trapped by the macrophage and DC
• DC activated by Ag will move to the T cell areas to presnt Ag to T cell and initiate adpative immune response.

• Gut associated lymphoid tissue.
• Includes tonsils, adenoids, appendix, and Peyer's patch that lines the small intestines

• Mucosa-associated lymphoid tissue
• Function is to trap pathogens to acticate lymphocytes.
• Pathogen arrives at mucosa-associated lyphoid tissues by direct delivery across the mucosa (mediated by M cells).

• Detect pathogen
• Initiate innate and adaptive immune response
• Generate igA secreting effector B cells
• Effector and memory lymphocytes generated in PP will home specifically to mucosal tissues and mucosal lymphoid organs rather than peripheral lymph nodes.

To enhance neutrophil's ability to phagocytes of the innate immune system.

as opsinin to facilitates phagocytosis.

They are plasma proteins that coats the bacteria or extracellular virus particles to make them easily phagocytosed.

Opsonization by C3b

• Macrophage express this toll-like receptor.
• When there is an infection it send signals to the macrophage's nucleus to change the pattern of gene expression. Such as genes for cytokines to induce innate immune response and inflammation at the site of infection are switched on.
• Lead to the production of either inflmmatory cytokines or anti-viral type 1 interferons

They are transmembrane proteins that has a extracellular domain that recognizes the pathogen and a cytoplsmic signaling domain that converys that information to the inside of the cell.

Starts the transcription of genes encoding inflammatory cytokines.

• From the help of other proteins (MD2 and CD14)
• MD2 is sensitive to LPS

TRIF

MyD88 and TRIF

Recruits neutrophils and basophils to infected area. (innate immunity)

• Activates NK cells. (innate immunity)
• To fight against viral infections

lose blood volume

lose blood leukocytes

• Short lived dedicated killers that circulate in the blood awaiting a call from a macrophage to enter infected tissue
• A type of granulocyte
• Most abundant WBC
• They form creamny pus at infected wounds and sites of infection.

• Produce by most cell types during innate immune response.
• Stop viral infection by infected cell and signal neighboring uninfected cells to prepare.

degrades viral RNA in the process of interferon type I

PKR prevents viral protein synthesis and the production of new infectious virions (prevent protein transcription)

IFN-gamma or type II interferons

it activates macrophages to secrete cytokines to help activate T cells which lead to adaptive immune response. Once T cell is activated, T cell send out IL-10 to turn off IFN-gamma.

Pro-inflammatory cytokine response --> neutrophil response --> pathogen killing

more IFN response --> antiviral effects

engulfed bacterias