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What are the 4 functions of the immune system?
- 1. Dectecting pathogen invasion
- 2. Initial innate immune response
- 3. Inflammatory response
- 4. Activate the adaptive immune response (T,B cells)
What are two types of microorganism in the human body and state their purpose.
- 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
Name 4 examples of pathogens that cause human disease.
- parasites (protozoans and worms)
What are the common pathogen's routes of infection?
- 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.
Name 2 sites of pathogen replication.
- Extracellular infection: mucosal surfaces tissues interstitial
- Intracellular Infection: cell cytoplasm, endosomal vesicles, or nucleus
When there is an infection in the interstitial spaces, blood, or lymph what organism are the pathogens and what are the protective immunity?
- a. Viruses
- b. Bacteria
- c. Protozoa
- d. Fungi
- e. Worms
- Protective Immunity
- a. Complement
- b. Phagocytosis
- c. Antibodies
When there is an infection in the epthelial surfaces what organism are the pathogens and what are the protective immunity?
- Pathogen: Bacteria, worms
- Protective immunity: Antimicrobial peptides (defesin), Ab (IgA)
When there is an infection in the cytoplasmic (intracellular) what organism are the pathogens and what are the protective immunity?
- Pathogens: Viruses, Bacteria, Protozoa
- Protective Immunity: NK cells, Cytotoxic T cells
When there is an infection in the vesicular (intracellular) what organism are the pathogens and what are the protective immunity?
- Pathogen: Bacteria
- Protective Immunity: T cell and NK cell depedent macrophage activation
2 Types of pathogen infections
- Acute infection
- Chronic Infection
What are the factors that affect the type of infection you get?
- Pathogen replication strategy
- Host immune response
- Pathogen immune evasion and immune suppression
When infection occurs, how do you know when you get infected?
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).
When the pain is recognized, then what?
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.
What are the three tiers of the immune system?
- Anatomical and Physiological Barriers
- Innate Immunity
- Adaptive Immunity
What does the anatomical and physiological barriers provide?
- 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)
What happen if you don't have a barrier resistance?
You will die quickly cause by infections.
Describe Innate Immunity.
- It is there all the time.
- Quick response.
What are effector cells?
Eats bacteria, kill virus infected cells, attack protozoan parasites
What is complement?
It helps the effector cells by marking pathogen with molecular flags and also attack pathogens.
Describe the pathogen invasion process.
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.
What are cytokines?
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).
What happens when cytokines causes local dilation of blood capillaries?
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.
What is the adapative immune response?
- 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.
What are lymphocytes?
WBC that helps the innate immune response slow the the spread of infection.
What do PAMP have to help PRR recognize it?
- Surface components
- Nucleic acid
- Metabolic and replication products
What is the site of infection for B cells called?
- epitope - linear, conformational
- Linear: recognize a stretcher of peptide (1,2,3,4,5, next to each other)
- Conformational: recognize a shape
What does the B cell recognize?
Recognizes native antigen through cell surface Ig receptor (BCR).
What do T cell recognizes?
Recognizes processed antigen presented on MHC of Ag presnting cell (APC) by T cell receptor (TCR).
What are Antigens?
- 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
What is the benefit of having both innate and adaptive immunity?
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)
Compare and contrast innate immune response vs adaptive immune response.
- 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).
What are T cell helper? (Th)
regulate immune response
What are cytotoxic ?
kill pathogen infected cells
What are regulatory T cell (Treg)?
control immune response
Where do leukocytes and RBCcome from?
Hematopoietic stem cells int he bone marrow.
Hemotopoietic stem cell
- Self renewing and can differientiate to different cells
- 3 common lineage:
- 1. Common Lymphoid progenitor
- 2. Common Myeloid Progenitor
- 3. Common erythroid megatkaryocyte progenitor
What do erythoid progenitor give rise to?
Blood cells: oxygen carrying erythocytes and the platele-producing megakaryocytes
What are platelets?
- Small non nucleated cell fragments of plate-like shape that maintian the integrity of blood vessels.
- Involve in blood clot to prevent blood loss.
What are megakaryocytes?
Giant cells with giant nucleus that are made by fusion of multiple precursor cells
Define the myeloid progenitor.
- 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
Why are granulocytes also called polymorphonuclear leukocytes?
because of the unique shapes of their nuclei.
what is the main function of Neutrophils?
- Phagocytose pathogens and fuse engulfed pathogens with granules that contain many anti-microbial agents to kill the pathogen.
- Circulate in the blood, short lived.
Do eosinophil, basophil, and mast cell have phagocytosis activities?
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.
Dendritic Cells (DC)
- 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.
What is the lymphoid progenitor?
- 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,
What are NK (natural killer) cells?
- 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
What are the cells of the innate immune system?
- Monocyte, Macrophage
- Neutrophil, Eosinophil, Basophil, and Mast cell
- Least abundant granulocyte
- Very rare, but regulate immune response
What are the cells of the adaptive immune system?
T and B lymphocytes
What cells of the innate immune system play a role in bridging the innate and adaptive immune system?
Macrophage and Dendritic cell
What is the purpose of blood circulation in the body?
- 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
Where are B and T lymphocytes originate from?
- 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.
How a lymph is made?
- 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.
Describe Lymphatic 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.
Why is important to have lymphatic circulation?
- 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.
What are the primary (central) lymphoid tissue?
- Bone marrow: produce of all leukocytes, B cell development and maturation, and T cell origination.
- Thymus: T cell development
What are the secondary (peripheral) lymphoid tissues?
- 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.
Where do B cell segregrate in the lymph node and what do they form when activated?
B cell segregrate in follicles of the lymph node and form germinal centers when activated.
Where is T cell located in the lymph node?
Where is macrophage and plasma located in the lymph node?
Through where does lymph from tissues enter in the lymph node?
They enter enter the draining lymph nodes through the afferent lymphatic vessel.
Where do the lymphocytes and lymph exit the lymph nodes?
Efferent lymphatic vessel
Through what does lymphocytes enter the lymph nodes?
High enthothelial venules (HEV) in the paracorticoid region of lymph nodes.
What is diapedesis?
The process where lymphocytes enters the lymph node.
Describe the process of how lymphocytes enter 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
What happens if pathogen or antigen enters the blood circulation?
The spleen will help out! :]
What does the spleen do?
- 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.
Name the components of the spleen and describe their functions.
- 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.
Describe the migration of lymphocyte in the spleen.
Blood - lymphocutes - trabecular artery - central arteriole - perifollicular zone
What is the function of the marginal zone of the spleen?
- 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.
What is GALT?
- Gut associated lymphoid tissue.
- Includes tonsils, adenoids, appendix, and Peyer's patch that lines the small intestines
What is MALT?
- 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).
What is the function of the Peyer's Patch (PP)?
- 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.
What is the function of adaptive effector Th17 of adaptive immune system?
To enhance neutrophil's ability to phagocytes of the innate immune system.
What does antibody function as?
as opsinin to facilitates phagocytosis.
What are complements?
They are plasma proteins that coats the bacteria or extracellular virus particles to make them easily phagocytosed.
What is the process of coating of a pathogen with a protein that faciliates phagocytosis called?
Opsonization by C3b
What are TLR4?
- 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
What are TLR?
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.
What are NFkB?
Starts the transcription of genes encoding inflammatory cytokines.
How does TLR4 recognizes LPS?
- From the help of other proteins (MD2 and CD14)
- MD2 is sensitive to LPS
What signal pathway does TLR3 uses?
What signal pathway does TLR4 uses?
MyD88 and TRIF
What do CXCL8 or IL-8 do?
Recruits neutrophils and basophils to infected area. (innate immunity)
What does IL-12 do?
- Activates NK cells. (innate immunity)
- To fight against viral infections
What causes hypotension?
lose blood volume
What causes neutropenia?
lose blood leukocytes
What does a neutrophil do?
- 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.
What are type I interferons?
- Produce by most cell types during innate immune response.
- Stop viral infection by infected cell and signal neighboring uninfected cells to prepare.
What are oligoadenylate synthetase?
degrades viral RNA in the process of interferon type I
Wyat are Protein Kinase R?
PKR prevents viral protein synthesis and the production of new infectious virions (prevent protein transcription)
What cytokine does NK cell releases?
IFN-gamma or type II interferons
What does IFN-gamma do?
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.
When there is a bacteria infection which cytokine is more likely to respond?
Pro-inflammatory cytokine response --> neutrophil response --> pathogen killing
When there is a viral infection which cytokine is more likely to respond?
more IFN response --> antiviral effects
What are phagosomes?