89 terms

MICRO 1.04 - Introduction to immunology

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Immunology
A branch of biomedical science that covers the study of all aspects of the immune system in all organisms
Immunology
Deals with the physiological functioning of the immune system in states of both health and diseases;

malfunctions of the immune system in immunological disorder
Immunology
Deals with host defense reaction to foreign (non-self) entities known as antigens (ANTIbody GENerator), antigen recognition molecules, and cell-mediated host defense functions
Immunity
Refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body
Microorganisms or their products
Foods, chemicals, drugs, pollen, or animal hair
Dander
Environmental agents include:
Morphology
Histologic Staining
Immunologic Functions
Intracellular and Cell Surface Markers
White blood cells can be distinguished on the basis of:
Surface immunoglobulin for B cells
T-cell receptors for T cells
o B and T lymphocytes can be distinguished by expression of surface antigen receptors:
CD
MHC I
MHC II
o Monoclonal antibodies are used to distinguish subsets of the different types of cells according to their cell surface markers
CD
Cluster of Differentiation + Numbers
MHC I
- all nucleated cells express
MHC II
- antigen-presenting cells (APCs) express
Dendritic Cells
Macrophage Family Cells
B lymphocytes
o Cells that present antigenic peptides to T cells include:
Innate lymphoid cells (ILCs)
are non-B, non-T lymphocytes that resemble T cells in some characteristics and include the NK cells
IMMUNE RESPONSE
collective and coordinated response to the introduction of foreign substances
Normal Immune System
there is a balance between infection and immunity (immunocompetence)
chronic viral infections
An imbalance can lead to
Hypo-responsiveness
results to infection
Hyper-responsiveness
can cause loss of self-recognition (auto-immune diseases)
Immunodeficiency
infection > immunity
innate immunity
Following infection, response of _____________, or the first line of immunological defense is stimulated
a disease process will follow suit
If the innate immune system fails to defend the body,____________
specific immunity
The __________________will then take the responsibility for the elimination of microorganisms
immunologic memory
In cases of re-infections, the specific immune system will provide immunity through its
______________(e.g. in cases of viral diseases like measles)
death of the host
Failure of both immunities to eliminate the offending microorganism will lead to __________
o Protection from invaders
o Elimination of altered self
SIGNIFICANCE OF THE IMMUNE SYSTEM
• Beneficial
o Discomfort (inflammation)
o Damage to self (auto-immunity)
SIGNIFICANCE OF THE IMMUNE SYSTEM
• Detrimental
1. innate
a. humoral - complement interferon, TNF

b.cellular - macrophage, neutrophil

2. adaptive
a. humoral - antibodies

b. cellular - T cells, effector cells
Immune system

1.
a.
b.

2.
a.
b.
• Non-specific
• Natural, native, non-adaptive
• Response is antigen independent
• There is immediate maximal response (no lag time)

• Rapid response
• Not antigen-specific
• Exposure results in no immunologic memory
INNATE IMMUNITY
• Specific
• Acquired
• Response is antigen dependent
• There is a lag time between exposure and maximal response
• Slow response
• Antigen-specific
• Exposure results in immunologic memory
ADAPTIVE IMMUNITY
Physical Barriers
• Skin, gut villi, lung cilia etc.

Circulating Molecules
• Complements

Soluble Mediators
• Macrophage derived cytokines such as interferon ɣ & α, TNF

Immune Cells
• Phagocytes, NK cell
• Eosinophils, K cells
INNATE IMMUNITY
Physical Barriers
• Cutaneous and mucosal immune systems
• Antibodies in mucosal secretions

Circulating Molecules
• Antibodies

Soluble Mediators
•Lymphocyte-derived cytokines
• Such as interferon ɣ

Immune Cells
• T and B lymphocytes
ADAPTIVE IMMUNITY
• Non-specific, natural, and native
• First line of defense against infections
• Resistance that is already present at birth and not acquired through antigen contact
• It is non-specific - used virtually against every possible invaders
INNATE IMMUNITY (NON-SPECIFIC)
Papillomavirus and Dermatophytes
exception of innate immunty
o Physical barriers (i.e. Skin and mucous membranes)

o Antimicrobial substances present in mucous membranes

o Phagocytic cells and eosinophils in the blood and tissues

o A class of lymphocytes called natural killer (NK) cells

o Various blood-borne molecules
Healthy individuals protect themselves against microbes by means of many different nonspecific mechanisms:
Defensin:
Lysozyme:
Lactoferrin:
Antimicrobial substances present in mucous membranes
DEfensin
can disrupt bacterial, viral and fungal membranes
lysozyme
lysis of bacteria by cleaving the polysaccharide backbone of the peptidoglycan of G+ bacteria
lactoferrin
Deprives microbes of free iron by binding to them. Remember na limiting factor nila ang Iron?
o Present prior to exposure to infectious antigens or other forms of macromolecules
o Unlike acquired immunity, exposure to antigens does not enhance its functions
o Does not discriminate among most foreign substances
characteristics of innate immunity
PAMPRs
• Innate responses are constantly being stimulated by the normal flora

• ___________on the cells of the intestine continuously see the LPS, LTA, flagella, & other components of the bacteria within the lumen
equilibrium
a state maintained between innate immune regulatory responses and their microbial stimuli
• Stratified squamous cells
• Sweat glands
• Sebaceous glands

function:
Desquamation
• Flushing
• Fatty acids
Effector mechanisms of innate immunity.

skin
Columnar cells



function:

Peristalsis
Low ph
Bile salts
Digestive enzymes
Defensins
Fatty acids
Effector mechanisms of innate immunity.

gi tract
Tracheal cilia


funtion:

Mucociliary elevator
Surfactants
Defensins
Effector mechanisms of innate immunity.

respiratory tract
• Mucus
• Saliva
• Tears


function
• Flushing
• Lysozyme
Effector mechanisms of innate immunity.

nasopharynx
eye
• Phagocytes
• Killer (K), natural killer (NK) & lymphokine activated killer (LAK) cells

function:
• Phagocytosis and intracellular killing
• Direct and antibody dependent cytolysis
Effector mechanisms of innate immunity.

blood and lymph
• Lactoferrin
• Transferrin
• Interferons
• TNF-α
• Lysozyme
• Fibronectin
• Complement



FUNCTION:

• Iron deprivation
• Antiviral proteins phagocyte activation
• Peptidoglycan
• Hydrolysis
• Opsonization, enhanced phagocytosis, inflammation
Effector mechanisms of innate immunity.

serum ad serous organs
• Acquired or specific immunity
• Elicited by contact with antigens
• Second line of defense against infection
• Soluble forms of antibody in the blood, body fluids or secreted from mucosal membranes can inactivate and promote the elimination of toxins and microbes.
• Epitope:
• A monoclonal antibody recognizes a single epitope
ADAPTIVE IMMUNITY (SPECIFIC)
Epitope:
• A monoclonal antibody recognizes a single epitope
an antigenic determinant that interacts with a single antibody molecule or TCR.
1. Immunologic Memory

o Acquired immunity remembers and recognizes each encounter with a microbe or foreign antigens, so that subsequent encounters stimulate increasingly effective defense mechanism

o Basis of vaccination - small amount of microorganisms of a particular disease (ie. Measles, polio) are introduced to the individual and the body "remembers" the foreign antigen




2. Specificity

o Amplifies the protective mechanisms of natural immunity, directs or focuses these mechanisms to the site of antigen entry → lead to elimination of the foreign antigen
2 important properties of adaptive
active
passive immunity
types of adaptive
ACTIVE IMMUNITY
• Form of immunity induced when specific immune responses are stimulated upon exposure or contact with antigens
bility to defend against the said antigens
adaptive immunity

active

• Regardless of antigen introduced, the host actively produces antibodies, and lymphocytes will acquire the a
• Examples:
o Natural active: infection (clinical or subclinical)
o Artificial active: vaccination
o Live organisms (small pox vaccine)
o Attenuated/weakened organisms (BCG)
o Dead organism (cholera, typhoid)
o Toxoid (tetanus)
o Modified virus (polio)
• Examples of active immunity
o Natural active:
o Artificial active:
o Live organisms
o Attenuated/weakened organisms
o Dead organism
o Toxoid
o Modified virus
• Advantage:
o Long-term protection (based on memory of prior contact with antigen and the capacity to respond faster and to a greater extent on subsequent contact with the same antigen)
advantage of adaptive active immunity
• Disadvantages:
o Slow onset of protection and the need for prolonged or repeated contact with the antigen
o May cause the disease to appear in very few cases after vaccination
disadvantage of adaptive active immunity
PASSIVE IMMUNITY
• Specific immunity given to an individual by transferring whole cells or immunoglobulin-containing sera from a specifically immunized individual (adoptive transfer)



• Transmitted by antibodies or lymphocytes preformed in another host (Horses form the Ig used in anti-rabies: ERIg)

• Administrated to provide immediate immunity to prevent incubation of deadly viruses
• Examples:
o Natural passive: transfer in vivo, colostrum
o Artificial passive: administration of immune serum (anti-rabies)
examples of adaptive passive immunity
• Advantage:
o Prompt availability of large amounts of antibody



• Disadvantage:
o Short lifespan of antibodies and possible hypersensitivity reactions if antibodies (immunoglobulins) from other species are administered
benefits of adaptive passive immunity
humoral
cell-mediated
LASSIFICATION OF ADAPTIVE IMMUNE SYSTEM
(BASED ON THE COMPONENTS OF THE IMMUNE SYSTEM)
HUMORAL IMMUNITY

B-lymphocytes

blood

extracellular microbes

Helper (CD4) T lymphocytes

B cells
• In the form of "ANTIBODIES" produced by____________

• Mediated by molecules in the
_______and is responsible for specific recognition and elimination of antigens

• Can be transferred to immunized individuals by cell-free portions of the blood (plasma or serum)

• Principal defense against ________________

• _______________recognize the pathogen's antigens complexed with class II MHC proteins on the surface of an antigen-presenting cell (macrophage or B cell) and produce cytokines that activate B cells expressing antibodies that specifically match the antigen

• The ____________ undergo clonal proliferation and differentiate to form plasma cells, which then produce specific immunoglobulins (antibodies)
T-lymphocytes4

cells from immunized individuals

intracellular pathogen

macrophage

helper (CD4) T lymphocytes

cytotoxic (CD8) T lymphocytes


cytokines
CELL-MEDIATED IMMUNITY
• Mediated by _________

• Can be transferred to unimmunized (naïve) individuals with _____________ but not with plasma and blood

• Important in host defense against _____________

• T lymphocytes activate
______________to kill intracellular microbes or destroy infected cells

• The antigen-MHC class II complex is recognized by ________________, while the antigen-MHC class I complex is recognized by
___________________

• Each class of T cells produces ____________, becomes activated, and expands by clonal proliferation
HUMORAL IMMUNITY
Antigen - Extracellular pathogens

Responding lymphocyte - B lymphocyte

Effector mechanism - Secreted antibody that will result to
elimination of bacteria

Transferred by - Serum (antibodies)
humoral
CELL-MEDIATED IMMUNITY
Antigen - Intracellular microbes in macrophage and cell

Responding lymphocyte - T lymphocyte

Effector mechanism - Activation of macrophage that will result to lysis

Transferred by - Lymphocytes
cell mediated
specificity
diversity
memory
self limitation
discrimination
cardinal featured of immune system
SPECIFICITY
• Specific antigens elicit specific responses
• Specific for different structural components of complex protein, polysaccharide and other antigens
• Determinant or epitopes: portions of antigens specifically recognized by individual lymphocytes
• Membrane receptors of lymphocytes can distinguish minutes differences between antigens
DIVERSITY
• Total number of antigenic specificities of the lymphocytes in an individual: lymphocyte repertoire
• Able to distinguish at least 109 antigenic determinants
• Results of variability in the structures of the antigen binding sites of lymphocyte receptors
• Different clones differ in antigen receptors
MEMORY
• Exposure of the immune system to a foreign antigen enhances its ability to respond again to that antigen
• Secondary immune responses: responses to 2nd and subsequent exposures to the same antigen which are usually rapid, larger and often qualitatively different from the 1st response (immunologic memory)
SELF-LIMITATION
• All normal immune responses wane with time after antigen stimulation
• When antigens are eliminated, stimulus is likewise eliminated
• Lymphocytes perform these functions for brief periods after stimulation, then remain as memory cells
• Feedback regulation
DISCRIMINATION
• Ability to distinguish between foreign antigens and self-antigens
• Tolerance
o Immunologic unresponsiveness
o Ability to recognize and respond to many foreign antigens but are normally unresponsive to the potentially antigenic substances in the individual
• Autoimmune Disease: abnormalities in the induction of self-tolerance
Immune response
Recognition of antigen
Activation of lymphocytes
Development of mechanism that mediate the physiological effects
Elimination of antigen
phases of immune system
COGNITIVE/RECOGNITION PHASE


B lymphocytes

T lymphocytes
• Binding of foreign antigens to specific receptors on lymphocytes that exist prior to antigenic stimulation

• ________________
o Produce antibody molecules on their surfaces that can bind to antigenic proteins, polysaccharides or lipid in soluble form
• __________________
o Express receptors only for short peptide sequences in protein antigens
o Recognize and respond only to peptides present on the cell surface
ACTIVATION PHASE

• Antigen-recognizing B lymphocytes differentiate into antibody secreting cells, and the secreted antibody binds the soluble (extracellular) antigen and triggers the mechanisms that eliminate the antigen.
• Some T lymphocytes differentiate into cells that activate phagocytes to kill intracellular microbes and other T lymphocytes directly lyse cells that are producing foreign antigens (i.e. viral proteins)
All lymphocytes undergo two (2) major changes in response to antigen:
1. Proliferate leading to expansion of the clones of antigen-specific lymphocytes and amplification of the protective response
2. Differentiate from cells whose primary function is cognitive to cells that function to eliminate foreign antigens
ACTIVATION PHASE
All lymphocytes undergo two (2) major changes in response to antigen:
1. By the antigen
2. By helper or accessory cells
A general feature of lymphocyte activation is that it usually requires two (2) types of signals:

1. Antigen recognition triggers numerous amplification mechanisms that rapidly expand the specifically responding cells and bystander cells.
2. Lymphocytes preferentially migrate to sites of antigen administration and immune responses.
Two (2) aspects of lymphocyte activation:
EFFECTOR PHASE
• The stage at which lymphocytes that have been specifically activated by antigens perform the function of elimination of the antigen
• Effector cells include lymphocytes that function in the effector phase
phagocytosis (opsonization)

plasma proteins termed complement

degranulation of mast cells

cytokines
Effector Functions:
o Antibodies bind to antigens and enhance their ________ by neutrophils and mononuclear phagocytes

o Activate system of ___________, which also participate in phagocytosis and cell lysis

o Stimulate __________ and release of mediators, responsible to combat infections and responsible for vascular components of acute inflammation

o Activated T lymphocytes secrete ______which enhance the function of phagocytes and stimulate inflammatory responses
CLONAL SELECTION HYPOTHESIS
• Form the cornerstone of the current concept of lymphocyte specificity and antigen recognition
• There are 109 number of antigenic determinants recognized by the mammalian system
• Every individual contains numerous clonally derived lymphocytes - each clone having arisen from a single precursor and being able to recognize and respond to a distinct antigenic determinant
• Antigen selects a specific pre-existing clone and activates it
CLONAL SELECTION HYPOTHESIS
• Form the cornerstone of the current concept of lymphocyte specificity and antigen recognition
• There are ____________recognized by the mammalian system
• Every individual contains numerous clonally derived lymphocytes - each clone having arisen from _________ to a distinct antigenic determinant
• Antigen selects a_________ and activates it
b cells

tcells
ARC
antibodies
CELLULAR BASIS OF IMMUNE RESPONSE
b cells
o Develop in the bone marrow in mammals
o Rearrange their immunoglobulin genes and express a unique receptor for antigen on their cell surface
o Migrate to a secondary lymphoid organ (ex. spleen) and may be activated by an encounter with antigen to become antibody-secreting plasma cells
t-cells
o Require maturation in the thymus and form several subclasses with specific functions
antigen recognition cells
o System capable of precisely distinguishing self from non-self, important in establishing immune response
antibodies
o Immunoglobulins which react specifically with the antigen that stimulated their production
o Make up about 20% of plasma proteins
o Made up of light and heavy polypeptide chains
IgA
o Main immunoglobulin in secretions such as milk, saliva, and tears and in secretions of the respiratory, intestinal, and genital tracts
o Protects mucous membranes from attack by bacteria and viruses
IgD
o Acts as an antigen receptor when present on the surface of certain B lymphocytes
o In serum, it is present only in trace amounts
IgE
o Fc region of binds to a receptor on the surface of mast cells and eosinophils
o Antigen-antibody complex triggers allergic responses of the immediate (anaphylactic) type through the release of mediators
o Serum is typically increased during helminth infections
IgG

IgG2
o Predominant antibody in secondary responses
o Only antibody to pass the placenta and is therefore the most abundant immunoglobulin in newborns
o Four subclasses , based on antigenic differences in the H chains and on the number and location of disulfide bonds
o ____is directed against polysaccharide antigens and may be an important host defense against encapsulated bacteria
IgM
o Main immunoglobulin produced early in the primary immune response (M = mauuna)
o Present on the surface of virtually all uncommitted B cells
o Most efficient immunoglobulin in agglutination, complement fixation, and other antigen-antibody reactions
o Has the highest avidity (strength of binding with antigens) of all immunoglobulins