Immune System Physiology Flashcards
Immune System - Function
Protects organisms from pathogenic agents and removes damaged component of the organism itself.
Complex collection of cells and organs that destroy or neutralize pathogens.
Types of Pathogens
Microorganisms that cause a specific disease. Virus Bacteria Fungi Parasites
Virus
Smallest, very specific. Either RNA or DNA.
Not living, cannot reproduce on their own (need a host).
Intracellular - has to enter the cell to reproduce (with cell’s metabolic machinery).
Infected cell lyses, releasing the virus to invade others.
Bacteria
Prokaryotic cells, generally harmless but some can cause infectious diseases.
Unicellular. Extracellular pathogen (grow in extracellular fluid). Reproduce on their own.
Gets eaten (phagocytosis).
Can release toxins, cause fever.
Fungi
Less common. Single or multi-cellular eukaryotic organism.
Mycoses: fungal infection in animals.
Causes infection such as athlete’s foot and ringworm.
Parasites
Less common. Invade host to obtain nutrients and harm it.
Protozoans: unicellular eukaryotic organisms.
Metazoans: multicellular animals.
Spread through vector or fecal-oral route.
Immune System - Composition
- Physical barriers: they prevent at all time pathogenic invasion into the body tissues.
- Lymphoid tissues: sites where leukocytes develop, reside and encounter foreign materials.
- Leukocytes or white blood cells.
Physical Barrier
• Non-specific defense • Prevent entry of pathogens • Hostile chemical environment (acidic pH discourages bacteria growth) Ciliated mucosa - Airway GI tract mucosa Skin
Lymphatic System - Functions
- Drain body fluids and return them to the bloodstream.
- Transport of dietary lipids and fat-soluble vitamins absorbed in the gut.
- Transportation and housing of the immune cells.
- Development of immune cells and of the immune response. (defense against pathogens)
Lymphatic System Circulation
Open system.
Capillaries leak → accumulation of interstitial fluid → interstitial pressure increases → spaces between cells open up → fluid enters lymphatic capillaries → becomes lymph → travels through lymph nodes → empty into larger lymphatic vessels.
Lymphatic Vessels
- Lymphatic trunks
- Lymphatic ducts
- Subclavian veins
Lymphatic capillaries empty into them.
Similar to veins, have valves.
Lymph Node - where?
Filter for lymph, where fluid can be exposed to immune cells.
Found near groin, armpit, neck, chest, and abdomen.
Central Lymphoid Tissue
Sites of leukocyte production and maturation:
- Bone marrow: all leukocytes developed here. B-cells
- Thymus: maturation site for T lymphocytes.
Peripheral Lymphoid Tissue
Where leukocytes contact pathogens and become activated.
- Lymph nodes: sites of adaptive immune responses & filters of lymph.
- Spleen: removes blood born pathogens.
- Lymphoid nodules: dense cluster of lymphocytes in areas routinely exposed to pathogens.
The 5 Types of Leukocytes
Granulocytes: - Neutrophil - Eosinophil - Basophil Lack granules: - Monocytes - Lymphocytes
Which immune cells are found in the tissue?
Macrophages, mast cells and dendritic cells.
Phagocytes
Neutrophils, eosinophils, monocytes, macrophage and dendritic cells.
Phagocytosis: removes extracellular pathogens and cell debris.
Lymphocytes
Provide immune system with diversity, specificity and memory!
Two Types of Immune Response
Innate immune response: relatively rapid but non-specific.
Adaptive immune response: slower, but highly specific.
Innate Immune Response - Function
- Prevent entry of pathogens
- Limit the spread of infection
- Eliminate pathogen (sometimes)
- Mediate start of adaptive immunity
- Contribute to the clearance of pathogen (phagocytosis always innate immunity)
Keep infection in check until adaptive immunity arrives.
Components of Innate Immunity
- Physical barriers
- Phagocytes
- Soluble mediators
- Natural killer cells
Cells of the Innate Immune System - Monocytes
Large mononuclear cells. 5-7% of WBC.
Differentiate into macrophages in tissue.
Phagocytic cells that act as a scavenger, can trigger inflammation.
Cells of the Innate Immune System - Dendritic Cells
Link between innate and adaptive immunity.
Antigen presenting cells. Call for help from t-cells.
Phagocytic cells.
Cells of the Innate Immune System - Neutrophils
Granulocytes → multilobed nuclei.
60% of WBC.
Phagocytic, extremely effective in killing bacteria.
Cells of the Innate Immune System - Eosinophils
0-5% of WBC.
Parasitic infections → release of granules kills pathogens too big to be eliminated by phagocytosis.
Cells of the Innate Immune System - Basophils and Mast cells
Involved in allergic reaction.
Contain granules with histamine and other inflammatory mediators.
Cells of the Innate Immune System - Natural Killer Cells
Lymphocytes that induce apoptosis in cells infected with intracellular pathogens, such as viruses or cancer
cells.
Soluble Mediators - Interferons
proteins involved in The Shut down and intense reduction of initiation translation, preventing virus production.
Soluble Mediators - Complement System
Composed of 30 plasma proteins that contribute to removal of pathogens (especially bacteria)
Activated in 3 ways:
- Formation of membrane attack complex (MAC).
- Opsonisation: Help phagocytes recognize pathogens.
- Increase inflammatory response.
Adaptive Immune Response
- Specificity: antigens are recognized by B and T cells. An infinite number of receptors to specifically
recognize every pathogen. - Immunological memory: protects the body from
getting diseases repeatedly from the same pathogen. - Self-recognition: capable of distinguish between self-antigens and foreign antigens.
What are the primary cells that control the adaptive immune response?
Lymphocytes, T cells and B cells (produce antibodies).
T - Cells Regions
Regulate B-cell activity. T-cells recognize antigens though t-cell receptors.
Constant region: similar among T-cells.
Variable region: assume extremely different and specific AA sequences, enabling recognition of multitude of antigens.
T - Cell Chains
Two chains.
Antigen-binding site: terminal end of both chains.
Each T-cell produces one type of receptor - specific for a single antigen or portion of antigen (epitope).
Pathogen Recognition by T - Cell
Do not recognize pathogens on their own.
The antigen needs to be processed and presented attached to specific protein: major histocompatibility
complex (MHC) molecule.
Major Histocompatibility Complex - Class I
Antigens derived from intracellular pathogens (viruses) are presented through MHC class I. Viruses infect nearly every tissue → almost all cells express MCH I. Cytotoxic T cells bind to MCH I.
Cytotoxic T Cells
Bind to class I MHC. Kill cells presenting those antigens by inducing apoptosis.
Major Histocompatibility Complex - Class II
Antigens derived from extracellular pathogens (bacteria, fungi) are presented through MHC class II.
Expressed by antigen-presenting cells - dendritic cells (eat it, chop it, show it to T cells in lymph nodes).
Helper T cells (Th) bind to MCH II.
Helper T Cells
Bind to MHC II, recognize antigens from extracellular pathogens.
Secrete cytokines (enhance other immune responses)
Th1 helps macrophages produce inflammatory response
Th2 help B cells produce antibodies.
B Cell
Can recognize native, unprocessed antigen, do not require participation of MHC and antigen-presenting cells.
B cell receptor are membrane bound antibodies.
Antibody
Recognize antigen on pathogen and bind to it. Phagocytes recognize antibody and perform phagocytosis.
Y -shaped. 4 protein chains: 2 identical heavy, 2 identical light.
Variable region (infinite), constant region (5).
Antigen
Protein (98% of the time) on pathogens that can be recognized by our immune system. Trigger immune response.
B Cell Proliferation
Stimulated when B cell binds to antigen.
Become either memory B cell or antibody synthesizing plasma cell.
Inactivation or Disposal of Antigen
- Neutralization: the antibody blocks an antigen’s activity just by binding to it.
- Agglutination: antigens are clumped together simultaneously by thousands of antibodies
- Opsonization: once bound to antibodies, an antigen is more susceptible to phagocytosis.
- Activation of NK cells: antibodies can mark cells or death by the killing action of NK cells
Generation of Diversity - Light Chain
Single exon codes for constant region.
Variable region coded by 2 exons Vk and Jk:
40 V genes joined to one of its 5 J genes.
Thousands of possible outcomes.
Generation of Diversity - Heavy Chain
Heavy chain is coded by 3 exons:
65 VH - 27 DH - 6JH → millions of possible outcomes.
How can there be infinite variables of receptors?
Thousands of possible outcomes for the light chain +
Millions of possible outcomes for the heavy chain.
In theory any heavy chain can be produced together with any light chain in a single B cell => 3.5 × 10(í 6. veldi) different antibody specificities.
Generation of Diversity - Somatic Mutation
Additional mutation during B-cell reproduction (successfully bound to antigen).
Generation of Diversity - Affinity Maturation
Mutated B cells that bind better will outcompete poorer binders.
Lymphocyte Development - Self Tolerance
Lymphocytes can be generated with specificity for any antigen, including self-antigens → dangerous, must be prevented from reacting → self tolarance.
Central Tolerance
Immature B cell recognizes self antigen → apoptosis or anergy.
T-Lymphocyte Development - Positive Selection
Only thymocytes able to bind self-MHC survive Recognition of MCH class I => CD8+ (Cytotoxic T cell) Recognition of MCH class II=> CD4+ (T helper cell)
T-Lymphocyte Development - Negative Selection
Dendritic cells present self-antigens to thymocytes.
Thymocytes that recognize self-antigens undergo apoptosis.
Loss of Self-Tolerance
The failure to inactivate or eliminate self-reactive cells leads to autoimmunity.
Immune system will attack our own tissue.
