Immunology (Body defenses)
Immunology
Immunity
❑ Immunity => the body’s ability to resist or eliminate potentially
harmful foreign material or cells
❑ Immune system
= internal defence system that can recognise, neutralise or
destroy “not normal self” material
= WBC and their derivative, + a variety of plasma proteins
Immunology
Functions of the Immune system
❑ Recognise and defend the body against foreign substances
❑ Immuno-surveillance => the recognition and destruction of
abnormal / mutant cells that arise within the body
❑ Removes old or dead cells
Immunity can either provide general resistance:
=> Non-specific, without memory, preformed, 1st line of def.
Or specific immunity:
=> Specific, has memory, inducible, diverse, and can
distinguish self from non-self
Immunology
Immunology
Leukocyte / White Blood Cells (WBC)
❑ Play a key role in body defence
❑ Classified into two groups (according to the appearance of the
nuclei and the presence/absence of granules)
1. Agranular WBC = lymphocytes (T- , B- ,and NK Cells)
= Monocytes
2. Granular WBC = Basophils
= Neutrophils
= Eosinophils
Immunology
Immunology
Functions of granulocytes
❑ Neutrophils => Phagocytic; first defenders against bacterial
invasion. Also use neutrophil extracellular traps (NETs)
❑ Eosinophils => regulate immediate-type hypersensitivity, so play
a role in allergic conditions such as asthma and hay fever.
> also attach to parasitic worms, then secrete
deadly substances to destroy them
❑ Basophils => Secrete histamines (for allergic reactions) and
heparin.
> Do not circulate, rather, dispersed in connective
tissue throughout the body
❑ These remain in blood for <1 day, then, 3-4 days in tissues
Immunology
Agranulocytes
❑ Monocytes => Phagocytic
=> Stay in blood for a day or two, then settle in
various tissues
=> mature into macrophages, live for months to yrs
❑ Lymphocytes => Involved in immune responses and production of
haemopoietic growth factors
=> B-lymphocytes = produce antibodies (markers)
antibody-mediated / humoral immunity
=> T-lymphocytes = destroy target cells directly
through cell-mediated immunity,
Immunology
Lymphoid Tissues
❑ All WBCs originate from a common precursor stem cell in the
bone marrow
❑ Except lymphocytes, which arise from lymphocyte colonies in
lymphoid tissue
❑ Lymphoid tissues => collection of tissues that produce, store, or
process lymphocytes
❑ incl. bone marrow, lymph nodes, spleen, thymus, tonsils, adenoids,
appendix and also aggregates of lymphoid tissue in the lining of the
digestive tract called:
Peyer’s patches, or gut-associated lymphoid tissue (GALT)
Immunology
Lymphoid Tissues
❑ intercept invading microbes early before they can spread
❑ e.g. lymphocytes in tonsil and adenoids
❑ respond to inhaled microbes
❑ E.g. In appendix and GALT
❑ Intercept microbes invasions in the digestive tract
❑ Lymph invaders are filtered through lymph nodes
❑ Spleen (largest lymphoid tissue) performs immune functions on
blood, similar to what lymph nodes do on lymph
❑ Spleen rids blood of microbes, worn out RBCs and foreign matter
❑ Thymus and bone marrow process T- and B-cells respectively
Immunology
Abnormalities in WBC production caused by:
❑ Toxic chemicals or excessive radiation
❑ slowed or stopped production, thus compromised defence
❑ Leukaemia (Blood cancer)
❑ Uncontrolled proliferation of WBCs, with inadequate defence ability
❑ results in inadequate immune capabilities
❑ Displacement of other blood cell lines in the bone marrow; anaemia
Immunology
REMEMBER!
Immunity can be General / innate:
❑ The body’s initial defense mechanisms against foreign invasion
(whether internal or external)
❑ Rapid, Non-specific; holds no memory of exposure; non-
adaptive, present at birth
❑ e.g. anatomical barriers and secretions (skin, nasal hairs, and
mucous membranes)
❑ e.g. chemical barriers (stomach acid, lysozymes in mucous,
nasal secretions, tears, saliva, etc)
❑ e.g. cellular responses (phagocytes, NK cells)
Immunology
REMEMBER!
Immunity can be Specific (acquired / adaptive):
❑ The body’s ability to recognize and remember specific pathogens
❑ develops as a result of exposure to pathogens
❑ Specific; holds memory of exposure; adaptive
❑ e.g. antibodies; memory cells such as B- and T-lymphocytes,
Check Yourself
What type of cell is primarily involved in the adaptive immune
response?
A. Neutrophils
B. Eosinophils
C. Lymphocytes
D. Basophils
Check Yourself
Innate immunity is present from birth.
A) True
B) False
Immunology
Immune responses
Two major components of the immune system’s response to
foreign invaders and other target:
❑ Innate immunity (General)
❑ Adaptive / acquired immunity
Check Yourself
Which of the following is a component of the innate immune
system?
A. B cells
B. T cells
C. Macrophages
D. Antibodies
Immunology
Innate defense includes
❑1. inflammation = non-specific response to tissue damage
and/or foreign invasion
❑2. Interferons = a family of proteins that non-specifically defend
against viral infections
❑3. The complement system = group of inactive plasma proteins
that destroy foreign cells by attacking their plasm membranes
❑4. Natural Killer Cells = specialised class of lymphocyte-like
cells that spontaneously and non-specifically lyse (rupture) and
destroy virus-infected cells and cancer cells
Immunology
Threat-associated agents that trigger innate immunity
Two patterns activate the innate response:
❑ PAMPs = Pathogen-associated molecular patterns (usually exogenous)
e.g. carbohydrate chains found on cell wall of bacteria
❑ DAMPs = Damage-associated molecular patterns (usually endogenous)
e.g. ATP released by trauma-damaged cells
Both trigger identical innate pathways to inflammation, tissue debris
removal and repair
Immunology
PAMPs (on bacterial cell wall) recognized by phagocytes
❑ are bound to pattern recognition receptors found on phagocytes
❑ Toll-like Receptors (TLRs) = receptors on phagocytes that match
threat-associated patterns (i.e. PAMPs)
❑ different kinds of TLRs for different kinds of threat-associated
molecular patterns
❑ TLRs allow phagocytes to ‘see’ pathogens, and recognise them as
non-self cells
❑ This recognition triggers phagocytosis; followed by recruitment of
other immune cells (often adaptive immunity related WBCs)
❑ thus, TLRs link innate immunity to adaptive immunity
❑ RLRs recognise viral D/RNA in host cell cytosol
❑ NLRs recognise bacterial fragments or paracytes
Immunology
1. Inflammation
❑ the goal => bring phagocytes and plasma protein to invaded /
injured site
❑1) isolate, destroy or inactivate invaders
❑2) remove debris
❑3) prepare tissue for healing and repair
❑ The inflammatory response typically happens in 5 steps
Immunology
Inflammation steps in response to injury and/or bacterial invasion
1. Defense by resident macrophages (phagocytosis and
chemotaxin secretion) in response to bacterial invasion
2. Localized vasodilation by means of mast cell-released
histamine to increase blood flow
3. Increased capillary permeability, arrival and entry of plasma
proteins into interstitial space and localized oedema, pain,
redness and heat
4. Diapedesis = the process whereby chemotaxins attract
neutrophils and monocytes, causing them to migrate from
blood vessels, through capillary pores, into the microbe-
infested interstitial space
5. Monocytes enlargement into macrophages, and opsonin-
marked bacterial destruction
Immunology
Recognition and destruction of bacteria
❑ Phagocytes don’t only use TLRs
❑ Opsonins = chemical mediators generated by the immune
system that mark foreign particles for phagocytic ingestion
❑ e.g. antibodies, complement molecules such as C3b
❑ Opsonins bind non-specifically to bacterium and specifically to
phagocyte, thereby enhancing phagocytosis
❑ This is called opsonization
Immunology
Destruction of bacteria by WBCs
❑ Use phagocytic and non-phagocytic means to clear area of
bacteria and cellular debris
❑ Pus is the collection of living and dead phagocytes, and liquified
necrotic tissue by lysosomal enzymes released from phagocytes
❑ Leukocytes secrete cytokines, which can recruit other immune
cells
❑ Phagocyte-secreted chemicals can:
❑ directly kill microbes (e.g. Nitric oxide)
❑ stimulate histamine release
❑ trigger both clotting and anti-clotting mechanisms
❑ stimulate synthesis and release of more neutrophils and lymphocytes
Immunology
Tissue Repair
❑ in regenerative tissue, cell division replaces lost cells
❑ in nonregenerative tissue, scar tissue formed by fibroblasts
❑ fibroblast divide rapidly and secrete collagen
❑ scars can form if complex underlying structure like hair follicles
and sweat glands are permanently destroyed
Immunology
Inflammation suppressing drugs
❑ Non-steroidal anti-inflammatory drugs (NSAIDs)
❑ e.g. Aspirin, Ibuprofen => these decrease histamine release and
inhibit prostaglandin production
❑ thus, reduce pain, swelling and redness
❑ Glucocorticoids
❑ Suppress nearly all aspects of inflammation
❑ Effective against undesirable immune reaction, like allergic reactions
❑ Work by destroying lymphocytes within lymphoid tissue and reduce
antibody production
❑ Downside = reduce the body’s ability to resist infection
Immunology
Innate defense includes
❑1. inflammation = non-specific response to tissue damage and/or
foreign invasion
❑2. Interferon = a family of proteins that non-
specifically defend against viral infections
❑3. The complement system = group of inactive plasma proteins
that destroy foreign cells by attacking their plasm membranes
❑4. Natural Killer Cells = specialised class of lymphocyte-like cells
that spontaneously and non-specifically lyse (rupture) and destroy
virus-infected cells and cancer cells
Immunology
2. Interferon
❑ released from virus-infected cells after exposure to viral nucleic
acid
❑ briefly provide non-specific resistance to viral infections by
interfering with the replication of the same or unrelated virus in
host cells
❑ bind to plasma membrane receptors of healthy neighbouring
cells
❑ this triggers production of virus-blocking enzymes, which can
break down viral mRNA, thus inhibit protein synthesis
❑ enzymes inactive until activated by viral nucleic acid
Immunology
Innate defense includes
❑1. inflammation = non-specific response to tissue damage and/or
foreign invasion
❑2. Interferons = a family of proteins that non-specifically defend
against viral infections
❑3. The complement system = group of inactive
plasma proteins that destroy foreign cells by
attacking their plasm membranes
❑4. Natural Killer Cells = specialised class of lymphocyte-like cells
that spontaneously and non-specifically lyse (rupture) and destroy
virus-infected cells and cancer cells
Immunology
3. The Complement System
❑ Activated in two ways,
❑1. Exposure to antibodies produced for and bound to a specific
invader (follows specific adaptive immunity pathway)
known as the classical complement pathway
❑2. Exposure to a particular microbial membrane-surface carbohydrate
pattern (follows non-specific immunity pathway)
known as the alternate complement pathway
❑ System has the ability to complement the actions of antibodies
❑ Forms membrane attack complexes (MACs) that punch holes
into victim cells
Immunology
MACs
❑ consists of liver-produced, inactive plasma proteins.
❑ Follows similar cascade-like activation as clotting factors
❑ C1 activated, then C2…… up to C9
❑ C5 to C9 assemble into doughnut-shaped protein complex, MAC
❑ MAC embeds itself in the surface membrane of nearby microbes
❑ Holes resulting from this cause influx of water into microbe cell,
resulting in it bursting.
❑ Takes 30 seconds
MACs
Immunology
Complement system augments inflammation
❑ its activated proteins
❑ serve as chemotaxins
❑ act as opsonins
❑ promote vasodilation and vascular permeability
❑ stimulate histamine release
❑ activate kinins
❑ Most of the activated proteins are unstable…
❑ they carry out the sequence only in the immediate area in which
they were activated, then decompose
Immunology
Innate defense includes
❑1. inflammation = non-specific response to tissue damage and/or
foreign invasion
❑2. Interferons = a family of proteins that non-specifically defend
against viral infections
❑3. The complement system = group of inactive plasma proteins
that destroy foreign cells by attacking their plasm membranes
❑4. Natural Killer Cells = specialised class of
lymphocyte-like cells that spontaneously and non-
specifically lyse (rupture) and destroy virus-
infected cells and cancer cells
Immunology
Natural Killer Cells (NK cells)
❑ Non-specifically destroy virus-infected cells and cancer cells
❑ lyse the membranes of these cells using chemicals
❑ similar in function to cytotoxic T cells, but act non-specifically
and are immediately available
Check Yourself
Which of the following is not a physical barrier in innate
immunity?
A. Skin
B. Mucous membranes
C. Antibodies
D. Stomach acid
Check Yourself
Which is not a characteristic of innate immunity?
A. Specificity
B. Immediate response
C. Involves barriers like skin
D. Involves cells like natural killer cells
Check Yourself
The innate immune system has the ability to recognize and
remember specific pathogens.
A) True
B) False