4c human body defences Flashcards
First line of defence the body has against disease
Skin and mucous membranes
Both physical and chemical barrier
Innate immunity is
Nonspecific immunity, includes external physical and chemical barriers by skin and mucous membrane
Includes antimicrobial substances, NK cells, phagocytes, inflammation and fever
Epidermis defense against disease
Closely packed keratinized cells is a great physical barrier
Shedding helps remove microbes
Bacteria can rarely get through without break in skin
Mucous membranes defense
Produce mucous to trap microbes and foreign substances
Contain cilia to clear mucous after
Coughing or swallowing ejects or destroys them
Lacrimal apparatus defense
Makes and drains tears
Blinking spreads tears, washing eyes with movement
Tears have lysozyme
Lysozyme locations
Saliva, perspiration, nasal secretions, tissue fluid
Saliva defense
Washes microbes from teeth and mucous membrane of mouth. Flow reduces colonization
Flow of urine defense
Retards microb colonization
Vagina juice defense
Move microbes out by washing and is acidic
Defecation vomiting defense
Expels bacteria. Smooth muscle contracts vigorously in response to toxins
Chemical protection in skin and mucous membranes
Sebum forms protective film, and unsaturated fats in it inhibit growth of some fungi and bacteria Fatty and lactic acids make skin pH 3-5 Sweat flushes microbes Gastric juice pH 1.2-3 (2.0) and has enzymes and mucous
Second line of defenses
Internal antimicrobial substances, phagocytes, NK cells, inflammation and fever
4 types of antimicrobial substances
Interferons
Complement
Iron-binding proteins
Antimicrobial proteins
Interferons
Alpha, beta, gamma IFN
Released by virus infected cells, diffuse to uninfected neighbours, and induce synthesis of antiviral proteins that interfere with virus replication.
Does not prevent them from entering cells
Complement system
Normally inactive proteins, when activated they enhance certain immune reactions
Iron-binding proteins
Reduce amount of iron for bacterial growth
Examples - transferrin (blood and fluid) lactoferrin (milk, saliva, mucus) ferritin (liver spleen red marrow) and hemoglobin (RBCs)
Antimicrobial proteins AMP
Short peptides, kill wide range of microbes, attract dendritic and mast cells. Microbes don’t develop tolerance to.
Antimicrobial proteins
Dermicidin (sweat)
Defensins and cathelicidins (by neutrophils, epithelia and macrophages)
thrombocidin (by platelets)
Natural Killer cells
Make up 5-10% of lymphocytes
Lack membrane molecules that identify B and T cells, but have ability to kill wide variety of infected cells and tumor cells
Attack any cells that display abnormal or unusual plasma membrane
Where are NK cells found
Spleen, lymph nodes, red bone marrow
How NK cells kill
Bind and release granules containing toxic substances
Perforin (a granule) inserts into plasma membrane and creates perforations for ECF to flow in and burst cell
Granzymes (a granule) Protein digesting enzymes that induce target to kill itself (but doesn’t kill microbes inside, phagocytes do)
Phagocytes
Neutrophils and macrophages (travel as monocytes and turn into an ultra robot enroute, called wandering macrophages)
There are also fixed macrophages which guard certain tissue
Where are fixed macrophages found
Histicocytes (connect tissue)
Stellate reticuloendothelial cells (kupffer cells) in liver
Alveolar in lungs
Microglial in nervous system
Tissue macrophages in spleen, lymph, red bone marrow
5 phases of phagocytosis
Chemotaxis Adherence Ingestion Digestion Killing
Activities of phagocytic cells
Marignation (selectins on endothelial cells bind to integrins on neutrophil as it rolls by)
Diapedsis (squeezing between endothelial cells)
Chemotaxis (directed migration to site of damage) where it then undergoes 5 phases of phagocytosis
Chemotaxis phase
Chemicals from invading microbes, white blood cells, damaged tissue, or activated complement proteins attract phagocytes
Adherence phase
Phagocyte binding to material
Enhanced by complement proteins binding to invading pathogen
Ingestion phase
Phagocyte plasma membrane forms pseudopod to ingest.
Pseudopod surrounds and fuses around invader, called phagosome
Digestion phase
Phagosome enters cytoplasm and merges with lysosomes (phagolysosome)
Lysosome releases lysozyme to break down microbial wall and other digestive enzymes that degrade carbs proteins fats and nucleic acids
Oxidative burst
Par of digestion, phagocye forms O2- (superoxide anion) hypochlorite (OCl-) and hydrogen peroxide h2o2 in process called oxidative burst
Killing phase
Everything is degraded, if it can’t be it remains as residual bodies
4 + 1 inflammation
Pain Heat Redness Swelling \+1 LOF
3 main stages of inflammation
Vasodilation and increased perm
Emigration of phagocytes from flood to ICF
Tissue repair
Histamine
Released by mast cells in CT, basophils, and platelets and also neutrophils and macrophages
Causes vasodilation and increased cap perm
Kinins
Polypeptides, from inactive precursor kininogens
Cause vasodilation, increased cap perm but also chemotactic properties.
E.G bradykinin
Prostaglandins
Released by damaged cells and intensify effect of histamine and kinin.
Stimulate emigration of phagocytes
Intensify and prolong pain caused by kinins
Leukotrienes
Produced by basophils and mast cells.
Cause increase perm, chemotactic properties for phagocytes
Complement
Different components of complement system release histamine, attract neutrophils, promote phagocytosis. Some can also destroy bacteria
Causes of pain in inflammation
Injury to neurons
Release of toxins from microbes
Kinins cause it
Prostaglandin gets the party wild and keeps the party going
Increased perm for clotting
Allows clotting factors through.
Fibrinogen ultimately converted to an insoluble, thick mesh of fibrin that localizes and traps invading microbes and blocks spread
Exudate
Fibrin, dead phagocytes, dead tissue, and serum
Fever definition
Abnormally high temp that occurs from hypothalamus being reset.
Triggered by cytokines like interleukin-1 released from macrophages
Intensifies interferons, inhibits microbe growth, speeds up reactions that aid repair
Adaptive immunity
Ability to defend self against specific invaders
Different than innate in:
Specificity for particular foreign molecules
Memory for most previously encountered antigens so that a second response is more rapid and vigorous
Antigens
In adaptive immunity
Antigen means antibody generator
They are recognized as foreign and provoke immune responses
B and T cells
Lymphocytes
Developed in red bone marrow and thymus from pluripotent stem cells that originate in red bone marrow
B cells mature in marrow
T cells come as pre-T and matured in thymus
Immunocompetence
The mark of a mature T or B cell
They have distinct proteins inserted into their plasma membranes, some are antigen receptors (for recognizing specific antigen)
Two types of adaptive immunity
Cell-mediated and antibody-mediated. Both triggered by antigens. Helper T’s help both
Cell-mediated adaptive immunity
Cytotoxic T cells directly attack invading antigens
Called humoral since it happens in fluids
Antibody mediated adaptive immunity
B cells turn into plasma cells which make antibodies (immunoglobulins)
Cell mediated best against
Pathogens (virus, bact, fungi) (and also what antibody mediated attacks)
Cancer cells
Foreign tissue transplants
*Always involves cells attacking cells
Clonal selection
Lymphocyte proliferates and differentiates in response to specific antigen.
Figures out how to fight invader, gets cloned many times (the huge number is what causes swelling of lymph)
Gives rise to effector and memory cells
Effector cells
Clones of a lymphocyte that destroy antigens
Include helper T, active cytotoxic T, plasma cells
Memory cells
Don’t actively participate, but if the same antigen is later noted clones more effector and memory cells
Same as effector, helper t, cytoxic t, plasma cells
Antigens two important characteristics
Immunogenicity (ability to provoke immune response)
Reactivity (ability of antigen to react specifically with the antibodies or cells provoked.
Immunologist definition
Antigens are substances with reactivity
Complete antigens have immunogenecity AND reactivity
Small part of antigen responsible for triggering response
Epitopes or antigenic determinants
Most antigens have many, each induces production of a specific antibody or activates a specific T cell
Chemical nature of antigens
Large, complex, usually proteins, but can be nucleic acids, lipo,glyco proteins and polysaccharides.
Large molecules with simply, repeating subunits(cellulose and most plastic)
Can use plastic in heart valves or joints
Hapten
Reactivity but not immunogenicity.
Can only stimulate immune response if attached to larger carrier molecule
E.g poison ivy and penicillin
Diversity of antigen receptors
Takes 35,000 genes and rearranges them (usually into 5-7 amino acids), can recognize a billion epiptopes doing this
Can also recognize epitopes not found in nature
Major histocompatibilty complex (MHC)
Transmembrane glycoproteins also called human leukocyte antigens (HLA)
Class 1 in all but RBCs and on body cell wall
Class 2 on antigen presenting cells only on surface
Urushiol
Substance on poison ivy, oxidized to quinone which is a hapten
Hapten drugs
Hydralazine (antihypertensive), causes lupus
Halothane (anaesthetic gas) - life threatening hepatitis
Antigen processing
Antigenic proteins broken down into peptide fragments, bind with MHC to tag for destruction
Exogenous and endogenous processing
Exogenous processing
APC cells recognize exogenous intruders (dendritic cells, macrophages, B cells)
APC eats antigen, breaks it down, mixes with MHC-II, presents antigen to T cells in lymh tissue saying go kill this fucker
Endogenous processing
Happens in a different order and with MHC-I but pretty similar to exogenous processing
For when virus make the cell shit bad stuff out, cancer, or toxins from bacteria
B and T location
T cells leave lymph to look for baddies
B cells stay put in lymph, spleen, mucosa associated lymph
Types of T cells in adaptive immunity
Helper T
Memory T
Cytotoxic T
Memory Cytotoxic T
Types of B cells in adaptive immunity
B cell
Plasma Cell
Memory B
APCs and T cells are also adaptive immunity
Characteristics of mature T and B cells
Immunocompetence (can recognize and respond to foreign antigens)
Immunotolerance (doesn’t kill you)
Helper Ts
APC brings antigen and MHC-II to inactive helper T
Cytoxic Ts
Infected body cell brings MHC-1 to inactivated cytotoxic T cell
Cell-mediated
Pathogens, some cancer, tissue transplants (CD4 helper Ts telling CD8 cytotoxic to muck shit up
Anti-body mediated
Extracellular pathogens (B cells to plasma cells)
CD 4 T cells
Helper Ts
Remain inactive until exogenous antigen fragments associated with MHC-II and CD4 stimulate to activate T
Makes active and memory T s
Active helper Ts
Produce cytokines
E.g interleukin-2 which is needed for all immune responses and prime trigger of T cell proliferation
IL-2 can be sostimulator for helper Ts or cytoxic Ts and NK cells
This is positive feedback
Memory Ts
Chill out until next attack where they rapidly proliferate into helper and memory Ts
Cytoxic T cells
CD8
Recognize those compatible with MHC-I
Attacks foreigners plus tumors and transplants
Activated by cytokines released from active helper Ts like IL-2
Cytotoxic T cells killing mechanism
Like NK cells, but they are targeted
Bind then release granzymes which are protein digesting that trigger apoptosis
Or bind an release perforin which creates channels for ECF
Or granulysin which enters through channels and creates holes in plasma membrane
Or lymphotoxin which activates enzymes in target cell which fragment DNA
Also cyto t’s release gamma-interferone to attract phagocytes and macrophage inhibiting factor to keep phagocytes there.
Immunological surveillance
If a cell produces a tumor antigen it can be destroyed by cytotoxic Ts, NK, and macrophages
Usually to kill cancer from cancer causing viruses
Immunosuppresive drugs from transplants make you ONLY more prone to virus cancers
Cell mediated vs humoral
Cell mediated is Ts humoral Bs
Activation and clonal selection of B cells
Can respond to unprocessed antigen but much better if its processed
Antigen taken into B cell, bind with MHC-II self antigen and moved to cell membrane where T cells produce interleukin-2 and other cytokines that function as a costimulator to activate B cells
Turn into plasma cells or memory cells
Plasma cells
A few days after exposure secrete hundreds of millions of antibodies till death 4-5 days later.
IL-4 and 6 (from helper Ts) helps proliferation, differentiation and secretion of antibodies from plasma cells
Each one recognizes only one antigen
Antibody
Secreted by plasma cells. Work lock and key like.
Glycoproteins called immunoglobulins, usually 4 polypeptide chains
Anti body polypeptide chains
Two heavy are identical to each other as are the two light chains
Disulfide bond holds each light chain to a heavy chain, and heavy chains together
Tips of H and L produce variable region where antigens bind
Remainder is called constant which differs between golf a m d and e and is a complement binding site and membrane binding site
IgM indicates recent invasion
IgG
80-85%, longest lasting
Blood, lymph, intestines
Bacteria and viruses by enhancing phagocytosis, neutralizing toxins, and triggering complement system
CAN cross placenta
IgM
5-10%, the biggest, found in saliva, reason for RBC ABO incompatability
First on scene
Activates complement, causes agglutination, and lysis of microbes
Agglunation
Process of an antigen mixing with its corresponding antibody
IgA
Predominant in normal secretions - tears, saliva, mucous, milk, intestinal secretions,
Prevents bacteria and viral attachement and invasion via mucous membranes
REDUCED during stress!
IgD
Detector
0.2%
Found on B cell surfaces and antigen receptor, it activatesB cells
IgE
Allergic response
Attaches to mast cells and causes histamine release
For parasytic worms
Systemic leads to anaphylaxis
Complement system
Involves a group of 30+ inactive proteins produced in the liver and activated by IgG and IgM
They cause phagocytosis, inflammation, cytolysis and prevent excessive damage to body tissues
C3 being activated
1 Inactivated 3 splits into C3a and C3b
C3b coats microbe (opsonization) which promotes attachment of phagocyte
C3b also splits C5 where C5b binds to C6 and C7 which attach to membrane of microbe
C8 C9 join the others and form a cylinder shaped membrane attack complex which inserts into plasma membrane
MAC creates channels resulting in cytolysis (blow it up with water)
C3a and C5a bind to mast cell for histamine release
C5a has chemotactic properties
How can C3 be activated
Classic - antibodies binding to antigens activates C1 which activates C3
Alternative - Lipid-carb molecules on surface of microbes and complement proteins B D and P interact to activate C3
Lectin - Macrophages digest microbes and produce chemicals telling liver to make lectin which binds to carbs on surfaces and activates C3
C3 inactivation
C3 is quickly broken down by proteins in blood and body cells to limit damage
Immunological memory
First time IgM quickly peaks, then a bit later IgG.
Second exposure IgG skyrockets rapidly (secondary response)
Self tolerance and recognition
T cells need to recognize MHC and (recognition)
lack reactivity from peptide fragments of own proteins (tolerance)
Positive selection
Some Pre T cells express TCRs that interact with self MHC on epithelial cells in thymic cortex, if not they undergo apoptosis
Negative selection
T cells interact with dendritic cells in thalamus, T cells survive if they do not respond to self antigens.
Negative selection occurs with deletion and anergy
Deletion
Self-reactive T cells undergo apoptosis and die
Anergy
Self reactive t cells survive but are unresponsive
only 1-5% percent survive this and deletion
B cell tolerance
through deletion and anergy as well. Usually a b cell released that binds with a self-protein lacks a cofactor and undergoes anergy
