Lecture 21 Immune system Flashcards
innative immunity
Each of a small set of receptors recognize a molecule absent from animals, but common to a type of pathogen
all animals have innative immunity, a defense active immediately upon infection
innate immuity includes barrier defenses (slide 6)
adaptive immunity
a sophisticated and precise defense mechanism in vertebrates, including humans, that provides a tailored response to specific pathogens or antigens. This type of immunity is highly specialized and develops throughout an individual’s life as a response to exposure to various pathogens, vaccines, or environmental factors.
(specificality and memory)
Each of a vast number of receptors is specific for a particular part of a protein in one pathogen, such as a surface protein of the influenza virus
The adaptive immune response is activated after the innate response and develops more slowly. (slide 6)
immune system functions
● Protects against pathogens:
○ Bacteria
○ Viruses
○ Parasites
● Protects against foreign molecules (e.g., toxins)
● Removes dead or damaged cells
● Attempts to recognize and remove abnormal cells
nonspecific immunity
does not target specific pathogen
-physical barriers
-inflammatory process
specific immunity and what types are there
identifies specific pathogen
-natural immunity: (innate) like allergies
recognition of traits shared by broad ranges of pathogens, using a small set of receptors
rapid response
-acquired immunity: active or passive
recognition of traits specific to particular pathogens, using a vast array of receptors
slower response
innate immunity defenses
barrier defenses: skin, mucous membranes, secretions
internal defenses: phagocytic cells natural killer cells, antimicrobial proteins, inflammatory response
what are the 2 adaptive immunity responses
humoral response: antibodies defend agains infection in body fluids
cell-mediated response: cytotoxic cells defend agains infection in body cells
innate immunity overview
● First-line defenses are barriers blocking entry If invaders breach, sensor systems detect
*Physical barriers - Skin and mucous membranes
● Sensor systems –
○ Sentinel cells use PRR (Pattern Recognition
Receptors) in cell membrane and cytoplasm
○ Complement system
● Innate defenses effectors work to destroy invaders
○ Interferons
○ Phagocytosis
○ Fever
Barrier defenses
● Skin and mucous membranes of the
respiratory, urinary, and reproductive tracts.
● Mucus traps and allows for the removal of microbes.
● Many body fluids including saliva, mucus, and tears are hostile to many microbes.
● The low pH of skin and the digestive system prevents growth of many bacteria.
Cellular Innate Defenses
Innate immune cells in mammals detect, devour, and destroy invading pathogens.
These cells recognize groups of pathogens using TLRs, or Toll-like receptors.
TLRs recognize fragments of molecules characteristic of a set of pathogens.
Hematopoietic stem cells (HSC found in bone marrow)
precursors where blood cells originate from
HSC maturing
Cytokines induce HSC to mature - Colony-Stimulating Factors (CSFs)
● Move around body, travel through circulatory systems
● Always found in normal blood increase during infections
● Some reside in various tissues
general categories for cells of the immune system
● Red blood cells (erythrocytes) carry O2
● Platelets (from megakaryocytes) involved in clotting
● White blood cells (leukocytes) important in host defenses
what are the 4 types of Leukocytes (white blood cells)
● Granulocytes
● Mononuclear Phagocytes
● Dendritic Cells
● Lymphocytes
granulocytes
contains cytoplasmic granules
● Neutrophils highest numbers, engulf and destroy bacteria,
other material (phagocytes)
● Basophils involved in allergic reactions, inflammation
– Mast cells similar; found in tissues, release histamines
● Eosinophils fight parasitic worms
– Also involved in allergic reactions
Monocytes
● Comprise mononuclear phagocyte
system (MPS)
● Monocytes (circulate in blood) and
cell types that develop as they
leave blood stream
● Dendritic cells and Macrophages
differentiate from monocytes
Lymphocytes
● Responsible for adaptive immunity
● B cells, T cells - specific in recognition of antigen
● Generally reside in lymph nodes, lymphatic tissues
● Natural killer (NK) destroy certain types of cells
Phagocytosis
the ingestion and digestion of foreign
substances including bacteria.
what are the 2 main types of phagocytic cells
these cells engulf and destroy pathogens, in mammalian body
- Neutrophils circulate in the
blood - Macrophages migrate
through the body or reside
permanently in organs and
tissues (slide 19)
Toll-like receptors: TLR
TLRs recognize fragments of
molecules characteristic of a set
of pathogens.
Inflammatory response
as pain and swelling, is brought
about by molecules released upon
injury or infection.
Mast cells
immune cells found tissues, release histamine, which triggers blood vessels to dilate and become more permeable (part of inflammatory response)
Local inflammatory response
1.Mast cells release histamines.
Capillaries dilate.
2.Neutrophils and anti- microbial
peptides enter tissue.
3.Neutrophils digest
pathogens and cell debris.
Tissue heals.
Inflammation - Cascade of events
- Dilation of small blood vessels
● Greater blood flow (heat, redness); slower flow rate
● Leakage of fluids (swelling, pain) - Migration of leukocytes from bloodstream to tissues
● Endothelial cells “grab” phagocytes, slow them down
● Phagocytes squeeze between cells of vessel (diapedesis) - Clotting factors wall off site of infection
- Dead neutrophils, tissue debris accumulate as pus
what causes inflammation?
Tissue damage results in inflammation
● Purpose is to
○ contain site of damage,
○ localize response,
○ eliminate invader
○ restore tissue function
what are the 5 signs of inflammation
Results in 5 signs
○ swelling,
○ redness,
○ heat,
○ pain,
sometimes loss of function
Cardinal signs of inflammation
- Rubor (redness) - increased blood flow
- Tumor (swelling) - exudation of fluid
- calor (heat) - increased blood flow, exudation of fluid, release of inflammatory mediators
4.Dolor(pain) - stretching of pain receptors and nerves by inflammatory exudates, chemical mediators - Functio laesa (loss of function) - pain, disruption of tissue structure, fibroplasia and metaplasia
local vs systemic inflammation
Acute inflammation
● short term
● mainly neutrophils
● macrophages clean up damage by ingesting dead cells and debris
If acute fails
Chronic inflammation
● macrophages, giant cells accumulate,
● granulomas form
Fever - an important host defense mechanism
Strong indicator of infectious disease, especially bacterial
● Temperature-regulation center in brain normally holds at 37°C but raises during infection in response to pyrogens (fever inducing substances)
● Growth rates of bacteria optimized for 37°C typically drop sharply above optimum, allows more time for defenses
● Moderate temperature rise increases rates of enzymes
● Enhances inflammatory response, phagocytic killing, multiplication of lymphocytes, release of attractants for neutrophils, production of interferons and antibodies, release of leukocytes from bone marrow
● White blood cells (macrophages) release chemicals that increase body’s temperature
● Divert blood from superficial blood vessels to body core – increase To
● 102-104oF (39-40oC)
Adaptations - Evasion of Innate Immunity by Pathogens
Modifying their surface to prevent recognition or phagocytosis
- Streptococcus pneumonia (meningitis) - outer capsule
Resisting breakdown following phagocytosis
- Mycobacterium tuberculosis -Tuberculosis (TB), another such disease, kills more than a million people a year
Adaptive Immunity
aka Acquired immune response
● activated later
● slow response
● Relies on lymphocytes
Receptors provide pathogen-specific recognition (what cells relate to this)
The adaptive response relies on two types of
lymphocytes, or white blood cells:
● T-cells - mature in the thymus, above the heart
● B cells -mature in bone marrow
What are antigens?
● substances that can elicit a B or T cell response
● T or B cells bind to antigens via antigen receptors specific to part of one molecule of that pathogen.
● The small, accessible part of an antigen that binds to an antigen receptor is called an epitope.
Antigen Recognition by B Cells and Antibodies
Each B cell antigen receptor is a Y-shaped molecule
● 2 identical heavy chains
● 2 identical light chains.
2 regions
● Constant (C) regions of
the chains vary little
● Variable (V) regions
differ greatly. Provide
antigen specificity.
Binding of an antigen activated B cells.
● B cell binds to epitope
● This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig).
● Different Ab recognize different epitopes
T cell antigen receptor
T cells bind to antigen fragments
displayed or presented on a host
cell.
These antigen fragments are
bound to cell-surface proteins
called major histocompatibility
complex (MHC) molecules.
MHC molecules are host
proteins that display the antigen
fragments on the cell surface.
Adaptive immunity has 2 components
the humoral immune response: (b cell) protects blood
the cell-mediated immune response: (t cell) destroy infected host cells
Cytotoxic T cells (type of T cell)
–TC induces apoptosis: proteases, cytotoxins (perforin)
–Releases cytokines to alert other cells
–Example - CD8
Helper T cells (type of T cell)
–Activates macrophages – giant cells
–Activate B cells
–Produce cytokines to direct and support T cells
–Example - CD4
CD4 is receptor for HIV, which infects TH
cells
Natural killer cells (type of T cell)
–Killing of infected cells tagged with antibodies
–Secrete IFN-gamma that stimulates macrophages
Cytotxic T cells
use toxic proteins to kill cells infected by viruses or other intracellular
pathogens before pathogens fully mature
Activation requires:
● signals from helper T cells
● interaction with an antigen-presenting cell (APC). Fragments of foreign proteins produced in infected host cells associate with class I MHC molecules and are displayed on the cell surface, where they can be recognized by activated cytotoxic T cells.
What do T-Helper Cells do (steps)
activates humoral and cell-mediated immune responses.
1. a foreign molecule must be present that can bind specifically to the antigen receptor of the helper T cell.
2. this antigen must be displayed on the surface of an antigen-presenting cell (APC) ie dendritic cell, macrophage, or B cell.
Activation of B Cells
Activation of B cells involves helper
T cells and proteins on the surface
of pathogens.
When an antigen binds a B cell, the
cell takes in a few foreign molecules
by receptor-mediated endocytosis.
The class II MHC protein of the B
cell then presents an antigen
fragment to a helper T cell, a
process that is critical to B cell
activation.
Antibody Function
● Antibodies do not kill pathogens; instead, they mark pathogens for
inactivation or destruction.
● In neutralization, antibodies bind to viral surface proteins,
preventing infection of a host cell.
● Opsonization - promotion of phagocytosis
Activation of B cells
slide 46
Humoral and Cell-Mediated Immune Responses
Both the humoral and cell-mediated responses can include primary and secondary immune responses.
Memory cells enable the secondary response.
Immunological Memory
Immunological memory is
responsible for long-term protections against
diseases.
Primary immune response
represents the first exposure to a specific antigen
a clone of lymphocytes
Secondary immune response
memory cells facilitate a faster, more efficient response
types of adaptive immunity
slide 54
immunization
Passive artificial
The projection provided by a second immune
response provided the basis for immunization.
Antigens are artificially introduced into the body to generate adaptive immune response and memory cell formation.
Immunizations are carried out with vaccines,
preparations of antigens from many sources.
Vaccination programs have been successful
against many infectious diseases.
Not all cells have the saem genome
slide 59 and 60
Generation of B and T Cell Diversity
● By combining variable elements, the immune
system assembles millions of different antigen
receptors from a small number of parts.
● An immunoglobulin (Ig) gene encodes the light
chain of the B cell receptor.
● Many different chains can be produced from the same gene by rearrangement of the V, J, and C regions.
Immunoglobulin (antibody) gene rearrangement
slide 62
adult stem cells
Many early embryos contain stem
cells capable of giving rise to
differentiated embryonic cells of any
type.
Adult stem cells can generate
multiple (but not all) cell types and
are used in the body to replace
nonreproducing cells as needed. (slide 64)
- Adaptive immunity is blocked or misregulated (allergies)
Exaggerated
(hypersensitive)
responses to
certain antigens
called allergens.
Adaptive immunity is blocked or misregulated (autoimmune disease)
● Immune system is active against particular
molecules of the body
● Loss of self-tolerance has many form
○ Lupus - histones and DNA released by the normal breakdown of body cells. These self-reactive antibodies cause skin rashes, fever, arthritis, and kidney dysfunction.
○ Type 1 diabetes - insulin-producing beta cells of the pancreas
○ Multiple sclerosis - myelin sheaths that encase many neurons
Adaptive immunity is blocked or misregualted (HIV Virus)
slide 69 ad 70
natural immunity:
-natural immunity: (innate) like allergies
recognition of traits shared by broad ranges of pathogens, using a small set of receptors
rapid response
acquired immunity:
active or passive
recognition of traits specific to particular pathogens, using a vast array of receptors
slower response
