6. immune responses

IMMUNE RESPONSES
PHYSIOLOGY: IMMUNO & HEME

ACUTE INFLAMMATION
OVERVIEW
‣ Inflammation describes the tissue response to injury and is a
series of processes initiated to limit tissue damage
‣ Acute inflammation is an innate and immediate response in the
short term following tissue injury
‣ Learning Goal
‣ To discuss the potential causes and signs of acute
inflammation, relevant tissue changes and immune cells
involved as well as outline some clinical conditions in which
this process occurs

ACUTE INFLAMMATION
CAUSES AND FEATURES
‣ Acute inflammation occurs in response to a variety of situations where there may be
tissue damage
‣ Common causes include infection, hypersensitivity reactions, physical or chemical
agents and tissue necrosis
‣ Acute inflammation has five main features:
‣ Rubor (redness)
‣ Tumour (swelling)
‣ Calor (heat)
‣ Dolor (pain)
‣ Loss of function

ACUTE INFLAMMATION
TISSUE CHANGES
‣ Blood flow changes
‣ In the first few seconds following injury, there is transient arteriolar vasoconstriction to control
any blood loss followed by arteriolar vasodilation to enhance blood flow in nearby capillaries
and tissues
‣ This provides blood components for managing the primary injury and initiating repair
‣ The higher blood flow causes the signs of rubor and calor
‣ Mast cells, basophils and platelets at the injury site release histamine
‣ This leads to the blood vessels becoming more permeable and the formation of
an exudate (protein-rich fluid) within the tissues
‣ The circulation is also slowed which, in combination with fluid exudation, increases the
concentration of red blood cells within circulation near the injury site
‣ These two changes lead to the sign of tumour

ACUTE INFLAMMATION
TISSUE CHANGES
‣ Exudation of fluid
‣ Exudation of fluid occurs due to Starling’s Law
‣ Vasodilation of arterioles leads to increased hydrostatic pressure and,
as a result, higher fluid movement out of vessels
‣ In addition to this, increased vessel permeability allows proteins to
move into the interstitium, leading to increased colloid pressure and
further increasing fluid movement out of vessels
‣ This increase in tissue fluid also leads to increased lymphatic
drainage, which can help remove damaging substances and causative
microbes

ACUTE INFLAMMATION
TISSUE CHANGES
‣ Exudation occurs as a result of several mechanisms:
‣ Endothelial contraction, mediated by histamine and leukotrienes
‣ Cytoskeletal reorganization, mediated by cytokines, IL-1 and TNF-α
‣ Direct injury, from toxic burns or chemicals
‣ Leukocyte-dependent injury, due to toxic oxygen species or enzymes from
leukocytes
‣ Increased transcytosis (channels across endothelial cytoplasm), mediated
by VEGF
‣ This fluid allows plasma proteins, such as fibrin, to be delivered directly to the
injury site

ACUTE INFLAMMATION
CELLULAR PHASE OF ACUTE INFLAMMATION
‣ The main immune cells involved in acute inflammation
are neutrophils
‣ The stasis of circulation allows neutrophils to line up along the
endothelium near the injury site, known as margination
‣ Next, they roll along the endothelium, sticking intermittently
‣ Following rolling, they attach more avidly to the endothelium,
known as adhesion
‣ Finally, the neutrophils migrate through the blood vessel walls

ACUTE INFLAMMATION
CELLULAR PHASE OF ACUTE INFLAMMATION
‣ Neutrophils can leave blood vessels through relaxation of
inter-endothelial cell junctions and digestion of the vascular
basement membrane
‣ Neutrophils move to areas of damage via chemotaxis
‣ This is often following a concentration gradient of
chemotaxins, including C5a, LTB4 and bacterial peptides
‣ Neutrophils are necessary as they can phagocytose pathogens
and cellular debris to remove them, facilitated by opsonins

ACUTE INFLAMMATION
HOW DOES ACUTE INFLAMMATION HELP?
‣ The changes that occur in acute inflammation help with controlling the
infection and restoring tissues to their normal state:
‣ Exudation of fluid helps deliver plasma proteins to injury sites and
also dilutes toxins and increases lymphatic drainage
‣ Infiltration of neutrophils leads to the removal of pathogens and
cellular debris
‣ Vasodilation, much like exudation, helps to increase the delivery of
necessary proteins and cells and to increase tissue temperature
‣ Pain and loss of function help to enforce rest and lower the risk of
further tissue damage

https://teachmephysiology.com/immune-system/immune-responses/acute-inflammation/

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following is NOT a chemotaxin?
‣ C5a
‣ VEGF
‣ LTB4
‣ Bacterial peptides

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following is NOT a chemotaxin?
‣ C5a
‣ VEGF
‣ LTB4
‣ Bacterial peptides
‣ VEGF is responsible for mediating increased transcytosis
in acute inflammation.

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following is NOT a clinical feature of acute
inflammation?
‣ Improved function
‣ Rubor
‣ Tumor
‣ Calor

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following is NOT a clinical feature of acute
inflammation?
‣ Improved function
‣ Rubor
‣ Tumor
‣ Calor
‣ Loss of function is found in acute inflammation.

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ What is the definition of chemotaxis?
‣ Directional movement of a phagocyte towards a chemical
attractant
‣ Activation of resting phagocytes by inflammatory
mediators
‣ Leucocytes assume marginal positions in blood vessels
‣ Production of collagenase by leucocytes to allow them to
exit blood vessels

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ What is the definition of chemotaxis?
‣ Directional movement of a phagocyte towards a chemical attractant
‣ Activation of resting phagocytes by inflammatory mediators
‣ Leucocytes assume marginal positions in blood vessels
‣ Production of collagenase by leucocytes to allow them to exit blood vessels
‣ The first option is the correct definition. "Activation of resting phagocytes by
inflammatory mediators" describes the process of activation of phagocytes.
"Leucocytes assume marginal positions in blood vessels" describes the process
of margination and "Production of collagenase by leucocytes to allow them to
exit blood vessels" describes the process of diapedesis.

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which mediator is responsible for increased blood vessel
permeability in acute inflammation?
‣ IgG
‣ C5a
‣ Histamine
‣ Opsonins

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ What is the main cell type found in acute inflammation?
‣ Eosinophils
‣ B cells
‣ Giant cells
‣ Neutrophils

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following is NOT a role of tissue exudate
formation in acute inflammation?
‣ Delivery of plasma proteins to the site of injury
‣ Dilution of toxins
‣ Reduces risk of further tissue damage
‣ Increases lymphatic drainage

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following describes the correct changes in pressures
leading to exudation of fluid in acute inflammation?
‣ Increase in hydrostatic pressure. Increase in colloid osmotic pressure.
‣ Decrease in hydrostatic pressure. Decrease in colloid osmotic
pressure.
‣ Increase in hydrostatic pressure. Decrease in colloid osmotic
pressure.
‣ Decrease in hydrostatic pressure. Increase in colloid osmotic
pressure.

ACUTE INFLAMMATION
REVIEW QUESTIONS
‣ Which of the following describes the correct changes in pressures leading to
exudation of fluid in acute inflammation?
‣ Increase in hydrostatic pressure. Increase in colloid osmotic pressure.
‣ Decrease in hydrostatic pressure. Decrease in colloid osmotic pressure.
‣ Increase in hydrostatic pressure. Decrease in colloid osmotic pressure.
‣ Decrease in hydrostatic pressure. Increase in colloid osmotic pressure.
‣ An increase in hydrostatic pressure leads to increased fluid movement out of
vessels. An increase in colloid osmotic pressure also occurs as proteins move
into the interstitium due to the increased permeability of vessels - this also
leads of increased movement of fluid out of vessels.

CHRONIC INFLAMMATION
OVERVIEW
‣ Inflammation is the tissue’s response to injury
‣ It describes a series of processes initiated to limit damage to tissue
‣ Chronic inflammation also arises as a response to injury but takes place
over a longer period of time than acute inflammation
‣ The process is more flexible than acute inflammation and has an
overlap with host immunity
‣ Learning Goal
‣ To discuss how chronic inflammation arises, the cell types involved
and clinical examples

HOW CAN IT ARISE?
‣ Chronic inflammation is a combination of inflammation, tissue injury and
repair
‣ There are a number of situations in which chronic inflammation may arise:
‣ Chronic inflammation may ‘take over’ from acute inflammation if the
damage does not resolve or the immune system fails to eradicate the
causative agent
‣ It may arise de novo, e.g. in autoimmune conditions such as rheumatoid
arthritis and lead to excessive or inappropriate immune system activation
‣ It may develop alongside acute inflammation in severe and persistent
irritation such as during recurrent episodes of acute inflammation

HALLMARKS OF CHRONIC INFLAMMATION
‣ Infiltration with mononuclear cells
‣ Macrophages, lymphocytes and monocyte replace neutrophils
‣ These cells have longer life-spans than neutrophils and so persist in the
tissue
‣ Tissue destruction
‣ This can be a result of prolonged exposure to pathogens, toxins or
immune cell activation
‣ Healing
‣ Damaged tissue attempts to heal through fibrosis and angiogenesis

CELLS INVOLVED
‣ The microscopic appearance of chronic inflammation is more varied than that of acute inflammation
‣ It is generally described in terms of the cells that are present:
‣ Macrophages
‣ Are present in acute and chronic inflammation
‣ They are important for phagocytosis, antigen presentation and cytokine synthesis
‣ Lymphocytes
‣ Have many immunological functions
‣ B cells differentiate to produce antibodies and T-cells have cytotoxic functions
‣ T-cells can also produce interferon-ϒ which recruits monocytes and activates macrophages
‣ Plasma cells
‣ Are differentiated antibody-producing B lymphocytes
‣ Their presence indicates that inflammation has been present for a considerable amount of time

CELLS INVOLVED
‣ Eosinophils
‣ Are often found in allergic reactions and parasitic infections
‣ Eotaxin recruits eosinophils which have granules containing major basic protein
‣ This is toxic to parasites and host epithelial cells
‣ Fibroblasts/Myofibroblasts
‣ Are recruited by macrophages
‣ They produce collagen to assist in healing and repair
‣ The morphology of chronic inflammation is fairly non-specific and the proportions of each cell
type will vary depending on the condition
‣ Eg. Plasma cells are prevalent in rheumatoid arthritis, whereas in chronic gastritis,
lymphocytes are typically more abundant

https://teachmephysiology.com/immune-system/immune-responses/chronic-inflammation/

GIANT CELLS
‣ Giant cells are multi-nucleated cells, made by the fusion of multiple
macrophages
‣ They form as a result of frustrated phagocytosis, which is when a
phagocyte fails to engulf its target
‣ There are several types, with some recognized in different conditions:
‣ Langhans Giant Cell in tuberculosis
‣ Foreign-body Type Giant Cell
‣ Touton Giant Cell in fat necrosis

GRANULOMAS
‣ Granulomas are a collection of epithelioid histiocytes (macrophages) that
may form in chronic inflammation
‣ They may also have associated lymphocytes or an area of central necrosis
‣ They arise as a result of persistent, low-grade antigenic stimulation
or hypersensitivity
‣ The immune system is unable to eliminate the substance and,
subsequently, attempts to ‘wall it off’ from the surrounding tissues
‣ Some examples of diseases which feature granulomatous inflammation
include: tuberculosis, leprosy and Crohn’s disease

EFFECTS OF CHRONIC INFLAMMATION
‣ Chronic inflammation can have several complications depending on
the area and underlying disease process
‣ These include:
‣ Fibrosis, e.g. chronic cholecystitis can lead to fibrosis of the gall
bladder wall
‣ Impaired function, e.g. inflammatory bowel disease
‣ Atrophy, e.g. atrophy of gastric mucosa in gastritis
‣ Stimulation of immune response, e.g. local and systemic immune
effects of rheumatoid arthritis

CLINICAL RELEVANCE - PULMONARY TUBERCULOSIS
‣ Tuberculosis (TB) is an infection typically caused
by mycobacterium tuberculosis
‣ It normally affects the lungs but TB can infect other areas
of the body
‣ Most cases are asymptomatic -> latent TB
‣ Around 10% of latent infections will progress to active
disease

‣ Common symptoms of active pulmonary TB include:
‣ Chronic cough
‣ Hemoptysis
‣ Fever
‣ Night sweats
‣ Weight loss

‣ Diagnosis of active TB is based on chest X-ray and Ziehl-Neelsen
staining of sputum (as mycobacteria do not grow on other stains)
‣ Tuberculin skin test identifies latent TB
‣ Treatment is complex and long-term
‣ Patients take a combination of Rifampicin, Isoniazid, pyrazinamide
and ethambutol for the first 2 months then continue on rifampicin
and isoniazid for the following 4 months
‣ Hint: use the mnemonic ‘RIPE’ to remember the above drug
combination

REVIEW QUESTIONS
‣ Which of the following conditions may feature
granulomatous inflammation?
‣ Ulcerative Colitis
‣ Crohn's Disease
‣ Rheumatoid Arthritis
‣ Osteoarthritis

REVIEW QUESTIONS
‣ Why do giant cells form in chronic inflammation?
‣ Tissue repair
‣ Hypersensitivity
‣ Frustrated phagocytosis
‣ To impair function

REVIEW QUESTIONS
‣ Which of the following stains is used to detect
mycobacterium?
‣ Ziehl-Neelsen staining
‣ Gram staining
‣ Haematoxylin and eosin staining
‣ Silver nitrate staining

REVIEW QUESTIONS
‣ What cell type are granulomas typically a collection of?
‣ Dendritic cells
‣ Plasma cells
‣ Myofibroblasts
‣ Epithelioid histiocytes

REVIEW QUESTIONS
‣ What cell type is typically most abundant in the
inflammation seen in Rheumatoid Arthritis?
‣ Macrophages
‣ Eosinophils
‣ Plasma cells
‣ Lymphocytes

REVIEW QUESTIONS
‣ Which of the following cells are NOT typically seen in
chronic inflammation?
‣ Macrophages
‣ Plasma cells
‣ Neutrophils
‣ Fibroblasts

REVIEW QUESTIONS
‣ Which of the following cells are NOT typically seen in chronic
inflammation?
‣ Macrophages
‣ Plasma cells
‣ Neutrophils
‣ Fibroblasts
‣ Neutrophils are typically seen within acute inflammation rather
than chronic inflammation and have a short lifespan of a few days.

REVIEW QUESTIONS
‣ What is the name for the type of giant cell found in fat
necrosis?
‣ Touton giant cell
‣ Langhans giant cell
‣ Foreign body type giant cell
‣ Osteoclastic tumour giant cell

AUTOIMMUNITY
OVERVIEW
‣ In order for the immune system to protect the body from pathogens, immune cells interact
to identify the presence of foreign antigens
‣ These foreign antigens act as red flags
‣ Normally, immune cells only react against foreign antigens, and healthy cells displaying
self-antigens do not trigger an immune response
‣ Immune tolerance refers to the unresponsiveness of the immune system to self-antigens
‣ This is crucial in order to avoid inflammatory reactions against healthy tissue
‣ Autoimmunity arises when there is a breakdown of immune tolerance
‣ Learning Goal
‣ To consider the mechanisms which maintain immune tolerance, and to discuss the
consequences of these mechanisms failing

AUTOIMMUNITY
MECHANISMS OF IMMUNE TOLERANCE
‣ The innate immune system provides non-specific protection
against anything it identifies as foreign by recognizing common
pathogenic features
‣ Conversely, the adaptive immune system is specific, with each B
and T lymphocyte receptor recognizing a unique foreign antigen
‣ The vast diversity of B and T lymphocyte receptors enables the
immune system to recognize a wide range of pathogens
‣ However, it inevitably results in the generation of self-reactive
lymphocytes

AUTOIMMUNITY
CENTRAL TOLERANCE
‣ To prevent self-reactive lymphocytes from causing damage, there are various checkpoints that
maintain immune tolerance
‣ Central tolerance is the first checkpoint
‣ This is the process by which self-reactive B and T lymphocytes are destroyed in the primary
lymphoid organs, namely the bone marrow and the thymus)
‣ For example, T lymphocytes developing in the thymus are exposed to self-antigens from a
range of tissues, such as proteins from the liver, pancreas and thyroid gland
‣ This ‘educates’ them about self-antigens
‣ T lymphocytes with receptors that react strongly with self-antigens are destroyed through a
process called negative selection
‣ Only those that do not react strongly with self-antigens are able to proliferate and leave the
thymus to circulate throughout the body

https://teachmephysiology.com/immune-system/immune-responses/autoimmunity/

AUTOIMMUNITY
PERIPHERAL TOLERANCE
‣ While central tolerance destroys most self-reactive lymphocytes, it is not a flawless process
‣ Some self-reactive lymphocytes escape negative selection and enter the circulation, where
they can cause tissue injury unless they are destroyed or suppressed in the peripheral tissues
‣ Therefore, peripheral tolerance is the next checkpoint in an attempt to prevent autoimmunity
‣ It includes deletion of self-reactive lymphocytes by apoptosis, suppression of self-reactive
lymphocytes by…
‣ Regulatory T cells -> Tregs: a specific type of T lymphocyte with immunosuppressive
effects
‣ Induction of anergy -> rendering lymphocytes unresponsive to self-antigens
‣ Interestingly, Tregs also play a crucial role in protecting the fetus, which has foreign paternal
antigens, from immune attack by maintaining maternal immune tolerance during pregnancy

AUTOIMMUNITY
LOSS OF IMMUNE TOLERANCE
‣ Despite all of these checkpoints, some people still develop autoimmune diseases
‣ These are thought to arise due to a combination of genetic and environmental factors
‣ Some of the main risk factors include:
‣ Genetic predisposition – autoimmunity often run in families, with the human leukocyte antigen
(HLA) gene family contributing to half of genetic predispositions
‣ Female sex – many autoimmune diseases are much more common in females of childbearing
age, suggesting that estrogen may affect the immune response
‣ Impaired Treg response – in certain autoimmune diseases, Treg numbers may be low or have
impaired function
‣ Infection – autoimmune conditions may be triggered by infection
‣ One interesting mechanism for this is molecular mimicry, in which the immune system fails
to distinguish between certain foreign antigens that are structurally similar to self-antigens
and attacks the self-antigens as well

AUTOIMMUNITY
CLINICAL RELEVANCE: MOLECULAR MIMICRY
‣ Clinical examples of molecular mimicry include:
‣ Rheumatic fever
‣ This develops after group A streptococcal infection such as strep
throat or scarlet fever
‣ This is due to antibodies made against the bacteria cross-reacting
with structurally similar self-proteins in the heart
‣ Guillan-Barré syndrome
‣ Often follows gastroenteritis with Campylobacter jejuni, with
antibodies cross-reacting with components of nerve cell membranes

AUTOIMMUNITY
FEATURES OF AUTOIMMUNITY
‣ Autoimmune diseases/autoimmunity affect around 5% of the population and include a diverse
range of more than 80 conditions, from rheumatoid arthritis to pernicious anemia
‣ While there are notable exceptions, autoimmune diseases tend to have certain features in
common
‣ These include:
‣ HLA genetic association
‣ Higher incidence among females
‣ Onset in young adulthood or middle age
‣ Detectable autoantibody levels
‣ Positive response to immunosuppressive treatments
‣ Fluctuations in symptom severity, with flare-ups and remissions

AUTOIMMUNITY
FEATURES OF AUTOIMMUNITY
‣ The spectrum of autoimmune diseases ranges from organ specific to non-organ specific
conditions, based on whether the self-antigen that the immune system is attacking is only
present in specific tissues or widely distributed throughout the body
‣ For example, Hashimoto’s thyroiditis is a classic organ specific condition, with the
autoimmune response limited to the thyroid gland
‣ In this condition, there are anti-TPO antibodies
‣ On the other end of the spectrum is systemic lupus erythematosus (SLE)
‣ Systemic lupus erythematosus (SLE) is a systemic condition caused by autoantibodies
‣ These target structures found in nearly all cell types, such as double stranded DNA
‣ For this reason, SLE can cause an array of seemingly unrelated and non-specific
symptoms, which can make it difficult to diagnose

AUTOIMMUNITY
REVIEW QUESTIONS
‣ In the context of autoimmunity, where does central
tolerance take place?
‣ Central nervous system
‣ Primary lymphoid organs
‣ Secondary lymphoid organs
‣ The systemic circulation

AUTOIMMUNITY
REVIEW QUESTIONS
‣ Rheumatic fever is a complication of which infection?
‣ Neisseria meningitides
‣ Haemophilus influenzae
‣ Group A streptococcus
‣ Staphylococcus aureus

AUTOIMMUNITY
REVIEW QUESTIONS
‣ What is the incidence of autoimmune diseases in the
general population?
‣ 0.5%
‣ 5%
‣ 15%
‣ 25%

AUTOIMMUNITY
REVIEW QUESTIONS
‣ Which of the following autoantibodies are found in in
systemic lupus erythematosus (SLE)?
‣ Anti-double stranded DNA antibodies
‣ Anti-parietal cell antibodies
‣ Anti-islet cell antibodies
‣ Anti-21-hydroxylase autoantibodies

AUTOIMMUNITY
REVIEW QUESTIONS
‣ Pernicious anaemia causes deficiency of which vitamin?
‣ Vitamin B1
‣ Vitamin B6
‣ Vitamin B9
‣ Vitamin B12

AUTOIMMUNITY
REVIEW QUESTIONS
‣ Which type of T cells are involved in maintaining
peripheral tolerance?
‣ T helper 1 cells
‣ T helper 2 cells
‣ Cytotoxic T cells
‣ Regulatory T cells

HYPERSENSITIVITY REACTIONS
OVERVIEW
‣ Hypersensitivity reactions are an overreaction of the
immune system to an antigen which would not normally
trigger an immune response
‣ The antigen may be something which would in most people
be ignored – peanuts, for example, or it may originate from
the body
‣ In either case, the damage and clinical symptoms result
from the body’s response to the substance rather than
damage caused by the substance itself

OVERVIEW
‣ The vulnerability of an individual to these reactions can
have a genetic link
‣ Overreaction to innocuous antigens are linked to changes
in the CD regions of T-helper cell membranes, explaining
why reactions like peanut allergies can commonly run in
families
‣ Overreaction to self-antigens is normally due to a failure in
central tolerance, and this failure can also have genetically-
inheritable features

OVERVIEW
‣ As is the case for many immune reactions, hypersensitivity reactions require
two separate interactions of the immune system with the antigen
‣ The first time an antigen enters the body, it is picked up by antigen-
presenting cells (such as macrophages or dendritic cells) and taken to the
nearest lymph node, where it is presented to naïve T-cells
‣ Cross-linking of the antigen with T-cells, as well as co-stimulatory molecules,
can lead to activation of that T-cell and subsequent differentiation into
“primed” Th1, Th2, or Th17 cells, which are specific to that antigen and can
stimulate further immune responses if they meet the antigen again
‣ It is this second meeting that could result in a hypersensitivity reaction

TYPES OF HYPERSENSITIVITY REACTION
‣ According to the Coombs and Gell classification, there are four main
types of hypersensitivity reaction
‣ Type 1
‣ In Type 1 hypersensitivity reactions mast-cell activation is induced by
secretion of IgE antibodies
‣ Initial exposure to the antigen causes the priming of Th2 cells, and
their release of IL-4 causes the B cells to switch their production of
IgM to IgE antibodies which are antigen-specific
‣ The IgE antibodies bind to mast cells and basophils, sensitizing them
to the antigen

‣ Type 1…
‣ When the antigen enters the body again, it cross links the IgE bound to
the sensitized cells, causing the release of preformed mediators
including histamine, leukotrienes and prostaglandins
‣ This leads to widespread vasodilation, bronchoconstriction, and
increased permeability of vascular endothelium
‣ The reaction can be divided into two stages – immediate, in which
release of pre-formed mediators causes the immune response, and
the late-phase response 8-12 hours later, where cytokines released in
the immediate stage activate basophils, eosinophils, and neutrophils
even though the antigen is no longer present

https://teachmephysiology.com/immune-system/immune-responses/hypersensitivity-reactions/

‣ Type 2
‣ Type 2 hypersensitivity reactions are mediated by antibodies
targeting antigens on cell surfaces
‣ When cell surface antigens are presented to T cells, an immune
response is started, targeting the cells to which the antigens are
attached
‣ Antibodies binding to cells can activate the complement system,
leading to degranulation of neutrophils, a release of oxygen
radicals, and eventual formation of membrane attack complex – all
of which lead to destruction of the cell

‣ Type 2 cont…
‣ Parts of the complement activation can also opsonise the target cell,
marking it for phagocytosis
‣ The destruction of host cells in this way can lead to tissue-specific
damage
‣ Type 2 hypersensitivity reactions may occur in response to host cells (i.e.
autoimmune) or to non-self cells, as occurs in blood transfusion reactions
‣ Type 2 is distinguished from Type 3 by the location of the antigens – in
Type 2, the antigens are cell bound, whereas in Type 3 the antigens are
soluble

‣ Type 3
‣ Type 3 hypersensitivity reactions are mediated by antigen-antibody complexes
in the circulation that may be deposited in and damage tissues
‣ The complexes may become lodged in the basement membranes of tissues
which have particularly high rates of blood filtration
‣ For example, the kidney and synovial joints being common targets
‣ Once lodged, the immune complexes rapidly and significantly activate
the complement chain, causing local inflammation and attraction of leucocytes
‣ Activation of complement results in increased vasopermeability, the attraction
and degranulation of neutrophils, and the release of oxygen free radicals
which can severely damage surrounding cells

‣ Type 4
‣ Type 4 hypersensitivity reactions are mediated by antigen-specific activated T-cells
‣ When the antigen enters the body, it is processed by antigen-presenting cells and
presented together with the MHC II to a Th1 cell
‣ If the T-helper cell has already been primed to that specific antigen, it will become
activated
‣ Subsequently, it releases chemokines to recruit macrophages and cytokines such as
interferon-γ to activate them
‣ Activated macrophages release pro-inflammatory factors, leading to local swelling,
oedema, warmth, and redness
‣ They also secrete lysosomal elements and reactive oxygen species, again leading to local
tissue damage

‣ Type 4 cont…
‣ CD8+ T cells may be involved in type 4 reactions where a foreign
antigen is detected on a cell, such as in organ rejection
‣ This is known as cell mediated cytotoxicity, and also results in
recruitment and activation of macrophages
‣ This reaction is also known as delayed-type hypersensitivity due to its
characteristic longer time period to appear following antigen exposure
‣ The reaction takes longer than all other types because of the length of
time required to recruit cells to the site of exposure – around 24 to 72
hours

REVIEW QUESTIONS
‣ What type of hypersensitivity reaction is anaphylaxis?
‣ Type 1
‣ Type 2
‣ Type 3
‣ Type 4

REVIEW QUESTIONS
‣ What is the typical amount of time taken for a Type 4
hypersensitivity reaction to develop?
‣ Seconds
‣ Minutes
‣ Days
‣ Weeks

REVIEW QUESTIONS
‣ Which cell is mainly responsible for mediating Type 1
hypersensitivity reactions?
‣ Mast cells
‣ Neutrophils
‣ Macrophages
‣ Monocytes

REVIEW QUESTIONS
‣ Which of the following cell types mediates Type 4
‣ Mast cells
‣ Neutrophils
‣ T cells
‣ B cells

REVIEW QUESTIONS
‣ Which of the following conditions is an example of a Type
3 hypersensitivity reaction?
‣ Anaphylaxis
‣ Acute Transfusion Reaction
‣ Contact Dermatitis

REVIEW QUESTIONS
‣ Which of the following conditions is an example of a Type 3
hypersensitivity reaction?
‣ Anaphylaxis
‣ Acute Transfusion Reaction
‣ Contact Dermatitis
‣ Anaphylaxis is a Type 1 hypersensitivity reaction. Acute Transfusion
Reactions are a Type 2 hypersensitivity reaction. Contact Dermatitis is a
Type 4 hypersensitivity reaction.

REVIEW QUESTIONS
‣ Which of the following is true regarding Type 2
‣ The antigens are soluble
‣ The antigens are cell bound
‣ The antigens are always foreign
‣ The antigens activate T cells

REVIEW QUESTIONS
‣ Which of the following is true regarding Type 2 hypersensitivity reactions?
‣ The antigens are soluble
‣ The antigens are cell bound
‣ The antigens are always foreign
‣ The antigens activate T cells
‣ The antigens are cell bound in Type 2 hypersensitivity reactions. They are
soluble in Type 3 reactions. Type 2 hypersensitivity reactions can occur to
both self and foreign antigens and involve the activation of neutrophils
rather than T cells.

REVIEW QUESTIONS
‣ Which of the following is NOT part of standard treatment
for anaphylaxis?
‣ Adrenaline
‣ Corticosteroids
‣ Non-steroidal anti-inflammatories
‣ Anti-histamines

REVIEW QUESTIONS
‣ Which of the following blood types could a patient with A
type blood receive in an emergency?
‣ A only
‣ A, B or O
‣ O only
‣ A or O

REVIEW QUESTIONS
‣ Which blood type is known as the “universal donor”?
‣ O
‣ A
‣ B
‣ AB

REVIEW QUESTIONS
‣ Which of the following hypersensitivity reactions occurs in
response to IgE?
‣ Type 1
‣ Type 2
‣ Type 3
‣ Type 4

IMMUNODEFICIENCY
OVERVIEW
‣ Immunodeficiency describes the failure of the immune
system to protect the body from infection, due to either
a defect in immune function or a deficiency in a
component of the immune system
‣ Learning Goal
‣ To discuss primary and secondary immunodeficiencies,
with reference to their pathophysiology and clinical
presentation

IMMUNODEFICIENCY
TYPES OF IMMUNODEFICIENCY
‣ Primary immunodeficiencies are rare and inherited
‣ They present early in life with severe, frequent or opportunistic infections
‣ They can be due to impaired production of components of the immune system or
due to a defect within existing parts of the immune system
‣ Secondary immunodeficiencies are more common than primary
‣ They may occur as a consequence of infection (e.g. HIV), immunosuppression (e.g.
chemotherapy) or malignancy
‣ They can also be secondary to disease states including diabetes
‣ These factors put stress on the body and weaken the immune system
‣ The signs and symptoms are the similar to primary immunodeficiencies, with
frequent, recurrent, and unusual infections

IMMUNODEFICIENCY
PRIMARY IMMUNODEFICIENCIES – B CELL
‣ B cell immunodeficiencies can be due to a failure in B cell
production, a failure to produce high affinity memory cells in
germinal centres, or failure to produce the usual spectrum
of antibodies
‣ They rarely cause illness until levels of maternal IgG fall at 4-6
months
‣ It typically presents with recurrent respiratory tract infections,
particularly with encapsulated pyogenic bacteria such as
Streptococcus pneumoniae and Haemophilus influenza B

https://teachmephysiology.com/immune-system/immune-responses/immunodeficiency/

IMMUNODEFICIENCY
PRIMARY IMMUNODEFICIENCIES – T CELL
‣ T cell deficiency can be due to reduced T cell counts, or
impaired activity
‣ This predisposes the sufferer to severe infections by
intracellular parasites, bacteria and viruses
‣ This can present with failure to thrive and/or diarrhea in
early life
‣ It is also associated with mucosal infection by yeasts such
as candida (the organism that causes thrush)

IMMUNODEFICIENCY
PRIMARY IMMUNODEFICIENCIES – NEUTROPHILS
‣ Neutrophil defects can be due to a deficiency in
neutrophil counts, or an impairment of neutrophil function
‣ Affected individuals present with severe extracellular and
gram negative bacterial infections that can be fatal, as they
respond very poorly to antibiotics
‣ These patients are especially prone to skin infections and
sepsis

IMMUNODEFICIENCY
PRIMARY IMMUNODEFICIENCIES – COMPLEMENT
‣ Defects in each of the complement pathways have different implications for the immune
system
‣ Deficiency in the classical pathway causes a build up of immune complexes in tissues and an
associated inflammatory response
‣ This causes diseases such as systemic lupus erythematosus and an increase in infection by
encapsulated bacteria
‣ Deficiency in the alternative pathway can cause severe bacterial infections and renal disease
‣ C1 esterase inhibitor deficiency (hereditary angioedema) is an autosomal dominant
inherited disorder which leads to sudden uncontrolled activation of complement and
bradykinin pathways
‣ This leads to recurrent spontaneous attacks of non-itchy angioedema, which can be life-
threatening if affecting the airway

IMMUNODEFICIENCY
PRIMARY IMMUNODEFICIENCIES – COMPLEMENT
‣ Terminal complement deficiency affects the production of C5-C9 complexes
‣ It is autosomal recessive and causes an inability to produce antigen-antibody
complexes, leading to defective opsonization and phagocytosis
‣ There is an increased risk of infection, particularly by Neisseria meningitidis and
Neisseria gonorrhoeae
‣ C3 deficiency causes impaired opsonization due to reduced levels of the opsonin
C3b
‣ This results in recurrent severe childhood infections, particularly by
encapsulated bacteria such as Neisseria meningitidis and Hemophilus influenza
‣ C3 deficiency is also associated with autoimmune diseases and type III
hypersensitivity reactions

IMMUNODEFICIENCY
REVIEW QUESTIONS
‣ How is agammaglobulinemia inherited?
‣ Autosomal recessive
‣ Autosomal dominant
‣ X linked
‣ Mitochondrial

IMMUNODEFICIENCY
REVIEW QUESTIONS
‣ What is the most common primary immunodeficiency?
‣ Agammaglobulinemia
‣ C3 deficiency
‣ Chronic granulomatous disease
‣ Selective IgA deficiency

IMMUNODEFICIENCY
REVIEW QUESTIONS
‣ Which disorder is associated with delayed umbilical cord
separation?
‣ Leukocyte adhesion deficiency type I
‣ Severe Combined Immunodeficiency (SCID)
‣ C1 esterase inhibitor deficiency
‣ DiGeorge syndrome

IMMUNODEFICIENCY
REVIEW QUESTIONS
‣ C3 deficiency is associated with which type of
hypersensitivity reaction?
‣ I
‣ II
‣ III
‣ IV

IMMUNODEFICIENCY
REVIEW QUESTIONS
‣ The production of which complement complexes are
affected by terminal complement deficiency?
‣ C1-4
‣ C5-9
‣ C3-6
‣ C2-5

IMMUNODEFICIENCY
REVIEW QUESTIONS
‣ Which of the following is not an encapsulated bacteria?
‣ Neisseria meningitidis
‣ Streptococcus pneumoniae
‣ Haemophilus influenzae
‣ Clostridium difficile

References
These slide reflect a summary of the contents of
TeachMePhysiology.com and are to be used for educational
purposes only in compliance with the terms of use policy.
Specific portions referenced in this summary are as follows:
‣ https://teachmephysiology.com/immune-system/immune-responses/acute-inflammation/
‣ https://teachmephysiology.com/immune-system/immune-responses/chronic-inflammation/
‣ https://teachmephysiology.com/immune-system/immune-responses/autoimmunity/
‣ https://teachmephysiology.com/immune-system/immune-responses/hypersensitivity-
reactions/
‣ https://teachmephysiology.com/immune-system/immune-responses/immunodeficiency/
Additional sources are referenced on the slide containing that
specific content.

6. immune responses

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