Lecture 1 Flashcards
What are the 3 fxns of the immune system?
- Protects from pathogens and foreign molecules
- Parasites, bacteria, viruses (protein coat surrounding genetic material)
- > Normally we want to target the pathogen directly and avoid damaging the host. However foreign molecule is eukaryotic e.g. fungi and cells are more similar to our own, it is much harder - Removes dead or damaged cells
- Attempts to recognize and remove abnormal cells
What are 3 pathologies of the immune system? Provide an example of each.
- Incorrect responses
- > Autoimmune disease (e.g. Type 1 diabetes) - Overactive responses
- > (e.g. Allergies) - Lack of response
- > Immunodeficiency disease (e.g. HIV/AIDS)
3 examples of pathogens?
- Bacteria
- Virus
- Fungi
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Slide 4
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What is tonsil?
Diffuse lymphoid tissue
Fxn of thymus?
Thymus produces T lymphocytes
Fxn of bone marrow?
Bone marrow produces most blood cells
What are 2 encapsulated lymphoid tissues?
- Lymph nodes
2. Spleen
What is gut-associated lymphoid tissue (GALT)?
A diffuse lymphoid tissue
What are the components of the lymphatic system?
Lymphatic system consists of lymph, lymph vessels and lymph organs
How are microorganisms trapped?
Reticular fibres trap microorganisms
How do macrophages and dendritic cells destroy microbes
phagocytosis
What is the primary means through which the immune system recognizes pathogens
GALT (e.g. Peyer’s patches and mesenteric lymph node) is the largest immune organ in the body and a primary means through which the immune system recognizes pathogens
What does the spleen contain that aids the immune system?
Spleen contains red and white pulp; red pulp removes aging RBCs and blood borne pathogens; white pulp houses T and B cells
Which organ combines innate and adaptive immune systems?
Spleen this combines innate and adaptive immune systems
What are the 3 innate ONLY cell types and their description and their fxn?
- Basophil
- Description: Granulocyte
- Fxn: Releases histamine that cause inflammation - Eosinophil
- Description: Granulocyte
- Fxn: Kills parasites with oxidative heat - Mast cell
- Description: Agranulocyte
- Fxn: Kils infected cells (often virus-infected) via cytolysis or apoptosis
What are the 2 adaptive ONLY cell types and their description and their fxn?
- Plasma cell, B cell
- Description: Aranulocyte (lymphocyte)
- Fxn: Recognizes antigens and produces antibodies - T cells (T helper TH cell, cytotoxic T lymphocyte CTL, T regulatory Treg cell)
- Description: Agranulocyte (lymphocyte)
- Fxn:
TH cells secrete cytokines. They are CD4+cells that bind MHC class II molecules on antigen-presenting cells (APCs).
CTKs recognize and kill specific “nonself” cells. They are CD8+ cells that bind to MHC class I molecules.
Treg cells are CD4+ cells that destroy cells that do not correctly recognize “self” cells.
What are the 4 cell types seen during the innate and adaptive immune system and their description and their fxn?
- Neutrophil
- Description: Granulocyte
- Fxn: Phagocytizes bacteria and fungi - Monocyte
- Description: Agranulocyte
- Fxn: Precursor to macrophage. Some macrophages are fixed to certain organs while others wander tissues, causing inflammation. All perform phagocytosis. - Dendritic cell
- Description: Many surface projections
- Fxn: In skin and respiratory and intestinal mucosa, phagocytizes bacteria and presents antigens to T cells. - Natural killer (NK) cell
- Description: Agranulocyte (lymphocyte)
- Fxn: Kils cancer cells and virus-infected cells
Describe and draw the hematopoiesis flow chart
- Pluripotent stem cells ->
a) Myeloid stem cell
b) Lymphoid stem cell - Myeloid stem cell ->
a) Erythrocyte (RBC)
b) Platelets
c) Mast cell
d) Eosinophil (granular leukocytes [WBCs])
e) Basophil (granular leukocytes [WBCs])
f) Neutrophil (granular leukocytes [WBCs])
g) Dendritic cell
h) Monocyte (agranular leukocytes [WBCs]) - Lymphoid stem cell
a) Monocyte (agranular leukocytes [WBCs])
b) T cell (agranular leukocytes [WBCs])
c) B cell (agranular leukocytes [WBCs])
d) Natural killer cell (agranular leukocytes [WBCs]) - Monocyte
a) Macrophage - B cell
a) Plasma cell
What are the 2 innate immune system barriers? Fxn?
- Epithelial layers
- Fxn: prevent entry - Defensins and cryptidins
- Fxn: Microbial killing
What are the circulating and tissue effector cells in the innate immune system?
- Neutrophils
- Fxn: Early phagocytosis and killing of microbes - Mast cells
- Fxn: Release of inflammatory granules - Macrophages
- Fxn: Efficient phagocytosis and killing of microbes: cytokines - Eosinophils
- Fxn: Nasty toxic cells that kill helminths (worms) - NK cells
- Fxn: Lysis of infected cells, activation macrophages
What are the circulating proteins in the innate immune system?
- Compliment (C’)
- Fxn: Killing of microbes, opsonization of microbes, activate leukocytes - Mannose-binding protein
- Fxn: Opsonization of microbes and activation of C’ - C-reactive protein
- Fxn: Opsonization of microbes and activation of C’ - Lyzozyme
- Fxn: Bacterial cell wall lysis
What are the cytokines of the innate immune system?
- TNF, IL-1, 6, 18
- Fxn: Inflammation: TNF = tumor necrosis factor, IL= interleukin - IFN a, b
- Fxn: Resistance to viral infection IFN = interferon - IFN g
- Fxn: Macrophage activation - IL-12
- Fxn: IFNg production by NK cells - IL-15
- Fxn: Proliferation of NK cells, memory T cells - IL-10, TGF b
- Fxn: Control of inflammation
What is the innate immune system (non-specific)? Consists of?
Innate immunity is generally considered to be the body’s first-line of defense against infection and consists of tissues, cells and soluble factors
What are the 3 physical barriers of the innate immune system?
- Skin
- Hair
- Secretions
What are the 5 types of cells in blood circulation, that are part of the innate immune system?
- Granulocytes (basophils, eosinophils, neutrophils)
- Mast cells
- Macrophages
What are the 3 types of cells in tissue and lymph that are part of the innate immune system?
- Monocyte
- Microglia
- Dendritic cells
What are the soluble factors in the innate immune system?
- Various complement proteins
2. Cytokines
What do dendritic cells resemble?
Dendritic cells have surface projections that resemble the dendrites of neurons
Innate immune cells are _____ throughout the body
ubiquitous
Where do innate immune cells tend to aggregate? Examples?
At interfaces btwn external and internal environments, (e.g., GI tract, lungs, skin)
How fast is the innate immune response?
Rapid (seconds to minutes)
Describe the 7 physical barriers in the innate immune system
- Skin
a) Epidermis
b) Dermis - Tear ducts/lacrimal glands:
- flushes out anything present. Drains into nasal pharynx - Ciliated escalator
- goblet cells produce mucous which goes over surface — - Earwax (cerumen)
- Prevents microbes from entering ear - Urine
- Cleans the urethra via flow - Vaginal secretions
- Move microorganisms out of vaginal tract - Peristalsis, defecation, vomitting, diarrhea
Describe the physical barriers in the innate immune system
- Sebum
- Forms a protective film and lowers the pH (3-5) of skin - Lysozyme in perspiration, tears, saliva, and urine
- Destroys bacterial cell walls - Low pH (1.2–3.0) of gastric juice destroys most bacteria and toxins
- Low pH (3–5) of vaginal secretions inhibit microbes
Define inflammation
- Features observed when an immune response is underway.
- Latin: rubror, calor, dolor, tumor.
- English: swollen, hot, red and painful region.
What are the steps during an inflammatory response? Does margination (sticking of phagocytes to endothelium) happen when the initial macrophages and phagocytes engulf and release the cytokines and other immune factors? When would vasoconstriction fit into this? Vasodilation?
- Bacteria/foreign invader in the infiltrated region will activate macrophages and phagocytes to engulf them. Activated macrophages and neutrophils (phagocytes) will release many chemicals that influence the immune response
- Attracts immune cells and other chemical mediators to site of infection
- Produce physical barrier to prevent infection from spreading
- Destroys injurious agent or limits its effects on the body
- Promotes tissue repair
- Histamines from mast cells: swelling, edema, vasodilation
- Interleukins: fever, migration of WBCs from blood vessels to site of infection
Describe the 6 steps in vascular rxns and phagocytosis?
- Chemicals such as histamine, kinins, prostaglandins, leukotrienes, and cytokines are released by damaged cells
- Blood clot forms
- Abscess starts to form
- Margination– phagocytes stick to endothelial cells
- Diapedesis– phagocytes squeeze btwn endothelial cells
- Phagocytosis of invading bacteria occurs
What is margination?
Phagocytes stick to endothelium
What is diapedesis?
Phagocytes squeeze between endothelial cells
What is the main fxn of fever?
Facilitate immune rxn (increase it). Don’t always get fever w/inflammatory response but with sufficient lvl of immune system mobility, fever will occur.
Monocytes circulate in the bloodstream; when leaving circulation become ______
macrophages
Examples of numerous specialized macrophage populations in different tissues
- Alveolar macrophages (lung)
- Histiocytes (connective tissue)
- Kupffer cells (liver)
- Mesangial cells (kidney)
- Microglial cells (brain)
- Tissue macrophage
Fxn of monocyte
Circulating precursor to macrophage
Fxn of macrophage
- Phagocytosis and killing of microorganisms
2. Activation of T cells and initiation of immune response
Describe the pathway involving phagocytosis of macrophages
- Chemotaxis and adherence of phagocyte to microbe. Chemotaxis allows phagocytes to migrate to infection site and destroy invading bacteria.
- Macrophage must find and bind to foreign invader. Recognition of pathogens by macrophages occurs through toll-like receptors that are able to recognize specific antigenic patterns on foreign invaders; but other receptors on macrophage. Phagocytose/ingestion of microbe by phagocyte.
- Formation of phagosome (phagocytic vesicle with foreign invader inside)
- Fusion of phagosome with a lysosome to forma phagolysosome
- Digestion of ingested microbe by enzymes in the phagolysosome
- Formation of the residual body containing indigestible material
- Discharge of waste materials
Example of macrophage receptors?
- LPS receptor-CD14
- Lipopolysaccharide
- Toll-like receptors
- Fc receptors
- Mannose receptors
- Complement receptors
- IFNgamma receptors
- Chemokine receptors
- Others
Fxn of macrophage receptors?
Function to mediate interactions between normal and altered self components, microbes; contribute to innate and adaptive immunity and homeostasis
Of the following molecular pattern of microbe, name the 1) source, b) pattern recognition receptor, c) principle innate immune response
- dsRNA
- LPS
- N- formylmethionyl peptides
- Mannose-rich glycans
- Phosphocholine and related
- CpG (PuPuCpGPyPy)
- dsRNA
- Source: Replicating virus
- Pattern recognition receptor: ds-RNA activated kinase and TLR3
- Principle innate immune response: IFNalphabeta - LPS
- Source: Gram-neg bacteria
- Pattern recognition receptor: LBP/CD14/TLR4
- Principle innate immune response: Macrophage activation - N-formylmethionyl peptides
- Source: Bacterial proteins
- Pattern recognition receptor: NFM receptors
- Principle innate immune response: Neutrophil and macrophage activity - Mannose-rich glycans
- Source: Microbial glycoproteins
- Pattern recognition receptor: MF mannose recptor, Plasma mannose, lectin
- Principle innate immune response: Phagocytosis, Opsonization, C’ activation - Phosphocholine and related
- Source: Microbial membranes
- Pattern recognition receptor: Plasma c-reactive protein
- Principle innate immune response: Opsonization, C’ activation - CpG (PuPuCpGPyPy)
- Source: Bacteria
- Pattern recognition receptor: ? TLR9/DNAPK
- Principle innate immune response: Macrophage activation
What receptor do mast cells have high affinity towards?
IgE
What are contained in the preformed granules of mast cells?
inflammatory mediators including: histamine; heparin; TNFa; chondroitin sulfate; neutral proteases; and others.
What do mast cells secrete?
- Preformed granules which contain cytokines to induce inflammation; chemokines to induce infiltration by monocytes, and neutrophils, leukotrienes to induce muscle contraction and increase vascular permeability (to allow diapedesis)
Describe how mast cells would fxn during immune response from innate system
- Bacteria trigger macrophages to release cytokines. Mast cells release histamines, which induce inflammation
- Vasodilation and inc vascular permeability cause redness, heat, swelling (erythema, edema), and pain
- Inflammatory cells migrate into infected tissue releasing more inflammatory mediators. Neutrophils and monocytes are recruited
