Immunology Flashcards
Immune system:
network of organs and tissues, cells and molecules designed to work together to identify and protect the body from infectious pathogens and other diseases
Primary organs:
(central or regenerative) -Contain developing lymphocytes -bone marrow, thymus
Secondary organs:
(peripheral) -contain more mature cells active in host tissue -spleen, lymph nodes, MALT; includes tonsils, adenoids, appendix, peyer’s patches in GI tract
_______ and ______ of immune system divided into two groups based on role in cellular development and host defense
ORGANS and TISSUES of immune system divided into two groups based on role in cellular development and host defense
Bone marrow is the site of ________ and ___________
Bone marrow is the site of HEMATOPOIESIS and B CELL MATURATION. -as a person ages, most hematopoiesis in flat bones
The ______ is a bi-lobed organ in the upper anterior thorax.
The THYMUS is a bi-lobed organ in the upper anterior thorax. -each lobe is divided into multiple lobules by fibrous septa. -each lobule has outer cortex and inner medulla -cells enter via blood, exit via lymphatic vessels or blood
Where do T Cells mature?
Thymus
Sail sign:
Infants have a much larger thymus - can be seen on x-ray in their top right chest.
What are the two sections of the spleen?
white pulp and red pulp
T cells are near arterioles in the _______ ______. B cells are more _______ in the white pulp.
T cells are near arterioles in the periarteriolar sheath. B cells are more peripheral in the white pulp.
What is red pulp involved in?
Red pulp is involved with red blood cell breakdown
Which organ is the major site of immune responses to pathogens and other foreign substances in the blood?
The spleen
what are lymph nodes?
-small, nodular aggregates of lymphoid tissue located along lymphatic channels/vessels
Describe the structure of lymph nodes:
-outer fibrous capsule -multiple afferent lymphatic vessels and one efferent lymphatic vessel -three concentric regions
What are the three concentric regions of lymph nodes?
cortex, paracortex, and medulla
What is the first organized lymph structure to encounter foreign antigens?
Lymph nodes
Fluid draining from the lymph node is enriched with _______ and ________.
Fluid draining from the lymph node is enriched with antibodies and many more lymphocytes.
What are the lymph node groups?
-Cervical -Supraclavicular -Axillary -Mediastinal -Supratrochlear -Mesenteric -Inguinal -Femoral -Popliteal
Cervical lymph nodes:
-Location: head and neck -Site of drainage: scalp, face, nasal cavity, pharynx
Axillary lymph nodes:
-Location: axilla -Site of drainage: Arm, chest wall, breast
Inguinal lymph nodes:
-Location: Groin -Site of drainage: genitalia, buttocks, anus, abdominal wall, leg
Mediastinal lymph nodes:
-Location: in/near mediastinum, central posterior thorax -Site of drainage: mid-chest, upper abdomen, lungs
Mesenteric lymph nodes:
-Location: lower abdomen, near intestine -Site of drainage: small and large intestine, upper rectum
What does MALT stand for?
Mucosal-associated lymphoid tissue
What is MALT?
aggregates of lymphocytes found throughout mucosal surfaces in body (GI, respiratory, and urogenital tracts)
GALT:
Gut-associated lymphoid tissue (tonsils, adenoid, appendix, Peyer’s patches)
BALT:
Bronchial/tracheal-associated lymphoid tissue
NALT:
nose-associated lymphoid tissue
VALT:
vulvovaginal-associated lymphoid tissue
Number of antibody producing cells in _____ is much larger than in all other tissues combined:
Number of antibody producing cells in MALT is much larger than in all other tissues combined
What tissue provides crucial defense against pathogens encountering mucosal surfaces?
MALT
How is lymph fluid similar/different to blood and blood flow?
-Lymph has white blood cells and plasma, but no red blood cells. -Lymph travels through branching and deep vessels, but is NOT a circular system like vascular system is. Smallest lymphatic vessels extend to tissues and have closed ends.
What are the main functions of the lymphatic system?
-Collect/drain excess fluid from surrounding tissue and return it to the vascular system -Absorb fat from the villi of the small intestine -Be a conduit for immune cells to and through the nodes back into circulation
Lymphatic drainage is initiated by WHAT?
interstitial fluid uptake in lymphatic capillaries
How does lymph flow?
-There is no “pump” -Flow by skeletal muscle contraction, arterial pulsation, unidirectional valves, smooth muscle in walls of larger vessels
Lymph flows through multiple ______ before entering circulation in the _____.
Lymph flows through multiple LYMPH NODES before entering circulation in the BLOOD.
Upper right lymph drainage system:
-Lymph from upper right areas of body (right side of head, heart, and lungs) drains to the right lymphatic duct which empties into the right subclavian vein
Lower/left body lymph drainage system:
Most of the body (besides right side of heat, heart, and lungs) drains into the thoracic duct, which then drains into the left subclavian vein.
How do the contents of lymph fluid change as the fluid progresses closer to circulation?
-phagocytic cells and antigens may be in lymph entering lymph node -Initiation of an immune response, processing of foreign antigens -fluid exiting nodes with higher number of immune cells and antibodies
Virchow’s Node:
left supraclavicular lymph node - palpate by running fingers over left clavicle. This is a super important node - you won’t be able to feel lymph node enlargement with any infection anywhere in the abdomen or left chest, but because of drainage the Virchow’s node will also be enlarged, and will alert you that something is going on in the left chest or abdomen. Abnormal for routine infections, so this patient would need x-rays/imaging. Always a concern for malignancy, especially in older populations.
Common disease processes associated with lymphatic vessels and nodes:
-lack of proper function of lymphatic drainage, can lead to lymphedema -also common problems associated with infection, blockage, malignancy
Lymphedema:
Interstitial collection of lymph due to disruption of lymphatic flow -usually progressive, can lead to tissue hypertrophy and fibrosis -swelling, skin changes, pain, restricted range of motion, and nonpitting edema -complications: skin infections, malignancy, reduced quality of life including aspects of emotional, physical, and social well-being
Primary lymphedema:
Associated with genetic or inherited conditions -associated with lymphatic disruption, can present at any age
Secondary lymphedema:
Due to underlying disease or is a consequence of prior treatment -in US, most due to malignancy or cancer therapy -etiology: obstruction of lymphatic vessels or nodes (compression by a tumor) or infiltration of the vessels by tumor cells; most common breast cancer)
Filariasis:
Most common cause of secondary lymphedema worldwide
Filariasis transmission:
-Due to infection by the nematode Wuchereria bancrofti -Infection is transmitted via mosquitos (adult worms reside predominantly in the lymphatic vessels and nodes, especially legs; scrotum is the top site in post-pubertal males
What is the standard method for diagnosing active infection?
The identification of microfilariae on a thick smear of blood (blood draw at night 10pm-2am, the time period when organisms are in peripheral blood -serologic enzyme immunoassay tests alternative test
The main goal of Filariasis treatment:
To kill the adult worm -DEC is both microfilaricidal and active against the adult worm; this is drug of choice for lymphatic filariasis -Lymphedema and elephantiasis are not indications for DEC treatment - most people with lymphedema are not actively infected with the filarial parasite
Lymphangitis:
Inflammation or infection of the lymph vessels -usually site of infection distal to the affected vessel -most common pathogen is streptococcus pyogenes
Chylothorax:
Term used for accumulation of lymph in the thorax -often consequence of severing the thoracic duct during surgery
Lymphadenopathy:
Enlargement (<1 cm) of one or more lymph nodes -localized - only 1 body area, generalized >2 body areas -lymphadenopathy can be associated with infection, inflammatory disorders, malignancy, etc.
Lymphadenitis:
Lymphadenopathy with pain and/or signs of inflammation (e.g. redness, tenderness) -usually associated with active infection
Lymphoma:
Type of cancer/malignancy of varied cells of the immune system
The first line of defense against microorganisms:
the intact skin and mucous membranes
the second line of defense against microorganisms:
the innate (natural) arm of the immune system
The third line of defense against microorganisms:
The adaptive (acquired) arm of the immune system (takes several days for this to become fully functional_
The two components of the adaptive arm of immunity are:
-Cell-mediated immunity -antibody-mediated (humoral) immunity
Innate responses use:
-Epithelial barriers -Phagocytic cells (neutrophils, macrophages, and dendritic cells) -cells that release inflammatory mediators (basophils, mast cells, and eosinophils) -and NK cells
Adaptive responses use:
Involve the proliferation of antigen-specific B and T cells, which occurs when the surface receptor of these cells bind to an antigen -APCs display the antigen to lymphocytes and collaborate with them in response to the antigen
Neutrophils type and function:
-WBC granulocyte -Engulf bacteria and fungi; oxidative burst
Monocyte/Macrophage type and function:
-WBC mononuclear (monocytes mature to macrophages in tissues) -Engulf bacteria, fungi, and cellular debris, produce cytokines, antigen processing
Eosinophil type and function:
-WBC granulocyte -Associated with allergic response and parasitic infection
Basophil type and function:
-WBC granulocyte -Associated with hypersensitivity and release histamine
Mast cell type and function:
-Bone marrow derived cell -Granules contain vasoactive amines like histamine, proteases kill bacteria
NK cell type and function:
-WBC lymphocyte -Recognizes stressed or infected cells and kills them by secreting macrophage-activating cytokine INF-gamma
B-cell type and function:
-WBC lymphocyte -Specific recognition of antigens as mediator of humoral immunity
T-cell type and function:
-WBC lymphocyte -Specific recognition of antigens as mediator of cell-mediated immunity
Macrophage origin:
Bone marrow derived
macrophage functions:
phagocytosis antigen presentation, effector phase of CMI
Macrophage locations:
lymph nodes, immune tissues, immune organs
dendritic cell origin:
bone barrow derived
dendritic cell functions:
-phagocytosis -antigen presentation, -initiation of T-cell responses
dendritic cell locations:
-lymph nodes -immune tissues -immune organs
follicular dendritic cell origins:
Mesenchymal derived
Follicular dendritic cell functions:
-Antigen presentation, -Display of antigens to B-cells in humoral immune responses
Follicular dendritic cell locations:
-Lymph nodes, -Spleen -MALT
What are the areas in the slide showing?
What is shown in this slide?
Cytokines bind to specific _______ receptors expressed by target cells, typically inducing ____________.
Cytokines bind to specific CYTOKINE receptors expressed by target cells, typically inducing SIGNAL TRANSDUCTION.
JAK-STAT signaling pathway:
- Major signaling pathway involved in immune regulation
- Cytokine interacts with cytokine receptor, activates signaling molecule JAK, this activates other molecules such as STAT
- STAT is a transcription factor - it moves into the nucleus, binds promoters, induces gene transcription
- new proteins stimulate target cell action/function
What does JAK stand for?
Janus Kinase
What does STAT stand for?
Signal transducer and activator of transcription
What cytokines are involved in innate immunity?
TNF-alpha, IL-1, IL-6, IL-12, IFN-a/IFN-B (type I IFNs), IFN-gamma (type II IFN)
Top pro-inflammatory cytokines:
TNF-a, IL-1, IL-6
Cytokines in Th-1 cells involved in adaptive immunity:
IL-2, IL-3, IFN-gamma
Cytokines involved in Th-2 cells in adaptive immunity:
IL-4, IL-5, IL-6, IL-10, TGF-B
Cytokines involved in hematopoiesis:
IL-3, IL-7, M-CSF, G-CSF, GM-CSF
Define chemokines:
Unique kind of cytokine; chemotactic cytokines
-Small chemo-attractant molecules that cause cells to migrate towards a concentration gradient of the chemokine
Target / responding cells of chemokines express ___________.
Target / responding cells of chemokines express CHEMOKINE RECEPTORS.
What are the four categories of chemokines?
Based on the position or arrangement of cysteine amino acids:
- Two major are CC and CXC (X is any other amino acid)
- Two other groups contain a single C or CXXXC motif
CXCL8 Cytokine:
Important for the recruitment of neutrophils
CXCL2 Cytokine:
Recruits naive T cells
CCL2 Cytokine:
Helps activate and recruit macrophages
Additional important molecules of the immune system:
- Commplement system
- Coagulation system
- Kinin system
- Protease inhibitors
- Defensins
Coagulation System:
Cascase of plasma enzymes which help form clots along with platelets and provide prostaglandins, hydrolytic enzymes, and growth factors that facilitate antimicrobial defense and wound healing
Kinin system:
Second enzyme cascade triggered by tissue damage (e.g. bradykinin, a vasoactive peptide that increases the supply of cellular and soluble substances to the site of infection)
Protease inhibitors:
Enzymes that cleave proteins and breakdown inhibitors (e.g. alpha-macroglobuln, helps prevent the dissemination of pathogens)
Defensins:
Antimicrobial peptides produced by a variety of cell types that can penetrate microbial membranes and destroy bacteria, fungi, and enveloped viruses
Key components of skin that make it a good barrier to pathogens:
- Physical/mechanical barrier (closely connected cells - keratinocytes - with cross-linked keratin)
- Chemical agents (skin has its own antimicrobial agents, like cathelicidins, defensins, dermicidin)
- Normal flora
Langerhans cells:
- Dendritic cells located among keratinocytes
- Derived from the bone marrow
- Function as antigen-presenting cells in immune responses to contact antigens (contact allergens) and some skin grafts
- Contain Birbeck granules
What is the image?
Birbeck granules
Mucosa layer of mucous membrane:
- Epithelium
- Lamina propria (loose CT with glands)
- Muscularis mucosae (smooth muscle)
Submucosa layer of mucous membrane:
Dense irregular connective tissue
Muscularis externa layer of mucous membrane:
- Inner smooth muscle
- Outer smooth muscle
External layer of mucous membrane:
- Adventita (loose connective tissue)
- Serosa (loose connective tissue with mesothelial lining from peritoneum
what type of junction is a tight junction?
An occludens junction
Tight junctions are composed of ______ and _______
Tight junctions are composed of CLAUDINS and OCCLUDINS (proteins)
What purpose to tight junctions serve?
- Prevent leaking between cells
- Prevents movement of membrane proteins
What type of junction is a zonula adherens?
An adherens junction
Zonula adherens are composed of ______
Zonula adherens are composed of CADHERINS
What do zonula adherens do?
Bind to actin of the terminal web (cytoskeleton)
What type of junction is a desmosome?
An adherens junction
What are other names for desmosomes?
Macula adherens or spot desmosome
Desmosomes are composed of _______ and _________
Desmosomes are composed of DESMOPLAKINS and PLAKOGLOBINS
Gap junctions are composed of ________
Gap junctions are composed of CONNEXINS
What type of junction is a hemidesmosome?
An adherens junction
What is the function of a hemidesmosome?
Connects the cell to the basement membrane, so it is not an intercellular junction
Components of mucosal immunity in intestines:
- Epithelial products (acidic pH, pancreatic enzymes, bile, intestinal secretions, mucus)
- Antimicrobial factors (lysozyme from Paneth cells in small intestine)
- Normal flora
- Lymphoid tissue
Step 1 of mucosal immunity in intestine:
Antigens in the gut lumen are bound by M cells (microfold cells) and undergo transcytosis into their intraepithelial pockets
Step 2 of mucosal immunity in intestine
Dendritic cells take up the antigen, process it, and present it to helper T lymphocytes
Step 3 of mucosal immunity in intestine
B lymphocytes are then stimulated to differentate into plasma cells which secrete IgA antibodies
Step 4 of mucosal immunity in intestine:
IgA is transported into the gut lumen where it binds its antigen on the surface of microorganisms, neutralizing potentially harmful invaders before they penetrate the mucosa.
How are IgA antibodies able to survive in the gut lumen?
IgA antibodies are resistant to proteolytic enzymes, so it can coexist with proteases in gut lumen
Components of mucosal immunity in oral cavity:
- Epithelium
- Lamina propria
- Saliva
- Tonsils
Describe how the epithelium works as a component of mucosal immunity in the ORAL cavity:
- Physical barrier like the skin
- Cells slough off and prevent biofilm formation
- Contains langerhans cells and intraepithelial lymphocytes
Describe how the lamina propria works as a component of mucosal immunity in the ORAL cavity:
- Contains macrophages
- Contains dendritic cells which project “dendrites” into the epithelium to uptake antigens and migrate to secondary lymphoid tissue and draining lymph nodes
Describe how the saliva works as a component of mucosal immunity in the ORAL cavity:
- Lysozyme (cleaves bacterial cell walls)
- Lactoferrin (complexes with iron, deprives microbes of nutrient)
- Histatins (inhibits growth of Candida albicans, inhibit growth of Streptococcus mutans - cause of dental caries)
- Salivary IgA (aggregates oral bacteria, prevents formation of dental plaques)
Pemphigus vulgaris:
- Acantholytic disorder in persons 30-60,
- Formation of severe intraepidermal bullae starting in oral cavity and spreading to skin,
- Autoimmune attack of desmosomes,
- Can be fatal
Bullous pemphigoid:
- Resembles pemphigus vulgaris but is much less severe,
- Features subepidermal bullae with characteristic inflammatory infiltrate of eosinophils,
- Autoimmune attack of hemidesmosomes
What are the two forms of diffuse lymphoid tissue:
- loose clusters of lymphoid cells,
- lymphoid nodules
Where is diffuse lymphoid tissue located?
Located in the mucosa (unless seen in enlarged form in submucosa known as Peyer’s patch)
Describe what you see in this image:
This is BALT tissue (bronchus-associated lymphoid tissue)
The arrow indicates the section of lymphoid tissue
Describe what you see in this image of a palatine tonsil:
See numerous aggregates of B cells. The tonsil is almost completely composed of lymphoid tissue
What is shown in this slide of the ileum?
__________ and ________ cause large particles to land on mucosal surfaces of the respiratory tract
TURBULENT AIRFLOW and HUMIDIFICATION cause large particles to land on mucosal surfaces of the respiratory tract
Mucus clearance in the respiratory tract is aided by:
- Coordinated secretion of mucins and proteins,
- Sufficient water for hydration,
- Beating cilia,
- Sneezing and coughing (soemtimes).
[A layer of mucus flows toward pharynx for expectoration or swallowing (a cleansing mechanism)]
What are 4 antimicrobial factors in the respiratory tract?
- Antioxidants,
- Defensins,
- Lactoferrins,
- Lysozyme
Vaginal epithelium secretes _________ that normal flora convert into _________, creating an acidic environment that is unfavorable for pathogenic microorganisms.
Vaginal epithelium secretes GLYCOGEN that normal flora convert into LACTIC ACID, creating an acidic environment that is unfavorable for pathogenic microorganisms.
The vagina contains some ___________ that form a protective biochemical barrier to infection
The vagina contains some ANTIMICROBIAL FACTORS that form a protective biochemical barrier to infection
Is normal urine sterile or unsterile?
Sterile
Normal urine is ______ for some bacteria due to its pH and factors such as urea
Normal urine is BACTERICIDAL for some bacteria due to its pH and factors such as urea
Tamm-Horsfall protein:
Protein from the kidney that binds bacteria and prevents attachment to urinary tract lining.
Host protection via frequent urination:
-Lower urinary tract is rinsed with urine 4-8 times a day, eliminating pathogenic organisms. (Neisseria gonorrhoeae and some strains of E. coli have virulence factors that allow them to bind to urinary tract epithelial cells)
The eye’s host barrier response to pathogens:
- Blinking,
- Lacrimal glands,
- Meibomian glands,
- Ciliary gland,
- Bacteriostatic/cidal tear film
Describe the bacteriostatic/cidal tear film and how it pertains to host barrier protection:
- Forms glandular secretions of conjunctiva and cornea; epithelium,
- Constant bathing of eyes with tears dilutes and clears foreign substances via tear ducts into the nasal passage
- tears contain lysozyme and other antimicrobial substances
