Immune response

• Immune response is a complex of

protective reactions, which helps organism
to maintain antigenic peculiarities and
cellular homeostasis during contacts with
external environment
 Immune response
Non specific (Innate immunity)
– It acts against various antigens.
– It is genetically determined and is characteristic for
species.
Specifc (Adaptive immunity)
– Reactions are specific against antigen. Immune
response is acquired by individual during its
contacts with various antigens.
It can be:
– Humoral
– Cellular
 Barriers against infection
• The simplest way to avoid infection is to
prevent the microorganism to enter the
organism:
• Skin
• Mucous membranes (gastrointestinal,
urogenital, respiratory)
 Mechanisms of Protection
• Mechanical:
• tight junctions between epithelial cells
• longitudinal flow of air or fluids;
• cilia of epithelial cells;
• mucus;
• peristalsis

• Chemical:
• acid in gastric juice,
• lysozyme in tears, nasal secretions, saliva;
• acidic environment on the skin;
• Microbial:
• competition between normal flora and pathogens for nutrients.
 Inflammation
• Inflammation is a complex of vascular
reactions in the connective tissue to the
exogenous and endogenous injurious
agents
Injury by
• Biological factors (microorganisms)
• Chemical factors
• Physical factors
Necrosis
 Inflammation
The signs of inflammation
by Celsus (25 BC—50 AD)
• Rubor
• Tumor
• Calor
• Dolor
by Virchow:
• Functio laesa
 Inflammation
Vascular phase:
• Transient vasoconstriction (few seconds)
• Vasodilatation - involves arterioles and
opening of capillary beds in the area
(histamine, NO.... ).
• Increased vascular permeability due to
formation of endothelial gaps in the
venules of microcirculation (histamine,
bradykinin, leukotriens…)
 Inflammation
Increased vascular permeability
Exudation of fluid from capillaries helps:
• Dilute toxic or irritating agents
• To bring antibodies, complement,
leukocytes...
 Inflammation
• An exudate is an inflammatory extravascular
fluid that has a high protein concentration, much
cellular debris, and a specific gravity above
1.020.
• A transudate is a fluid with low protein content,
most albumin, and specific gravity less than
1.012. It results from hydrostatic imbalance
across vascular endothelium, while permeability
of endothelium is normal
Edema – denotes an excess of fluid (exudate or
transudate) in the interstitial tissue
 Inflammation
Leukocytic events in inflammation:
A. Migration
• In the lumen of the vessel: margination, rolling,
adhesion
• Transmigration across endothelium
• Migration in interstitial tissues toward a chemotactic
agent
B. Phagocytosis
• Recognition and attachment (opsonization by C3b, IgG)
• Engulfment and formation phagosome and
phagolysosome
• Killing or degradation by toxic oxygen and nitrogen
products, lysozymes, proteases etc
 Inflammation
The inflammatory response involves vascular and cellular
events mediated by variuos mediators:
• Cytokines (produced by macrophagesTNF-alfa, IL-1, IL-
6, IL-8, IL-12…)
• Plasma factors (produced by liver) – acute phase
proteins, complement system, kinin system, coagulation
factors…..
• Vasoactive amines – histamine (mast cells, platelets,
basophils); serotonin (platelets); causes dilatation of
arterioles and increases permeability of venules.
• Arachidonic acid metabolites – prostaglandins and
thromboxane (cyclooxygenase pathway) leukotriens
(lipoxygenase pathway)
 Terminology
• Organ or tissue + itis
Bronchitis, myocarditis……
Exception pneumonia
 According to the exudate
inflammation is classified in:

Serous inflammation
(inflammatio serosa)
Purulent inflammation
(inflammatio purulenta)
Fibrinous inflammation
(inflammatio fibrinosa):
Hemorrhagic inflammation
(inflammatio haemorrhagica)
Types of inflammation according to exudate

Serous inflammation (inflammatio serosa)

Exudate is transparent with small amount of
desquamated epithelium or mesothelium
Causes: viruses (blisters in herpetic infection),
physical agents
Catarrhal inflammation (inflammatio
catarrhalis) is a serous inflammation in
mucous membranes. Catarrhus of upper
respirotary tract – rhinitis, nasopharingitis
Outcomes- healing or progress to other type,
most commonly purulent
Types of inflammation according to exudate

Purulent inflammation (inflammatio purulenta)

Pus or purulent exudate consists of neutrophils,
necrotic cells, bacteria, plasma proteins
Causes – pyogenic bacteria (staphylococcus,
streptococcus, Neiseria meningitidis, Neiseria
gonorrhoeae)
Forms of purulent inflammation
• Abscess (it has pyogenic capsule)
• Phlegmone
• Empyema
Outcomes: Healing; Abscessus can drain through
fistula; when tissue defect large – formation of
connective tissue or scarring; can develop sepsis; in
chronc inflammation can develop amyloidosis;
Abscessus cerebri
Appendicitis phlegmonosa
Empyema vesicae felleae
Empyema of the gallblader
Types of inflammation according to exudate

Fibrinous inflammation (inflammatio fibrinosa)

When is greater vascular permeability larger
molecules such as fibrinogen passes the
vascular barrier and fibrinogen is converted
to fibrin
Causes – bacteria (streptococcus pneumonia,
corynebacterium diphteriae, mycobacteria
tuberculosis, shigella dysenteriae), toxic
agents (uraemia)
Types of inflammation according to exudate
Fibrinous inflammation
Fibrinous inflammation can be in
• serous body cavities lined by mesothelium,
• mucous membranes,
• parenchymal organs (lungs)
Fibrinous inflammation is classified to:
• Fibrinous inflammation. It occures in serous body cavities and lungs
• Fibrinous ulcerative (dyphteric or pseudomembraneous
inflammation); it develops in diphteria, dysentery, uremia,
Outcomes – resolution (fibrinous exudate removed by fibrinolysis,
and other debris by macrophages; can be restored normal tissue
structure); organisation (fibrinous exudate is converted to
connective tissue; it leads to synechiae or adhesion formation in
serous cavities, can develop obliteration of the cavity);
Fibrinous ulcerative inflammation in respiratory tract can lead to
asphyxia;
Fibrinous ulcerative inflammation leads to scarring of mucous linings
 Pericardial adhesions
Obliteration of pericardial cavity
Types of inflammation according to exudate
Hemorrhagic inflammation
• Hemorrhagic inflammation (inflammatio
haemorrhagica) – exudate with great amount of
RBC
• Haemorrhagic feature can have other types of
inflammation (serous, fibrinous) when other
pathological states affecting small vessels
present; It can be in vit. C deficiency,
thrombocytopenia
• Causes: viruses, bacterial toxins (antrax, pestis);
medicines
• Outcomes depends on the main disease
Tracheitis haemorrhagica
 Course of non specific inflammation

Features Acute inflammation Chronic inflammation

Time From minutes till days Weeks, months, years
Signs Increased permeability of Proliferation of BV and
BV, leading to exudation, fibroblasts, formation of
accumulation of exudate granulation tissue
Dominating cells Neutrophils, eosinophils Macrophages,
lymphocytes, plasma
cells, mast cells.
 Lymphoid organs
Central or primary lymphoid organs
• Bone marrow and thymus
Peripheral or secondary lymphoid organs
• Lymph nodes, spleen, mucosa associated
lymphoid tissue

The peripheral lymphoid organs are the site

of lymphocytes activation by antigen
 Lymph node
• Lymphatics drain extracellular fluid (or
lymph) from peripheral tissues, through
lymph nodes

• Lymph carries antigen and antigen bearing

cells to the lymph nodes
Specific immune response cells
• T lymphocytes (T helpers: Th1 and Th2; T
cytotoxic cells)
• B lymphocytes → plasma cells→ IgG, IgM,
IgA, IgE, IgD
• Antigen presenting cells
Dendritic cells
Macrophages
B cells
 Major histocompatibility molecules

• The main physiologic function of the cell surface histocompatibility

molecules is to bind peptide fragments of foreign proteins for
presentation to T cells
• Class MHC I and MHC II are cell surface glycoproteins involved in
antigen presentation
• Class MHC I molecules are expressed on all nucleated cells and
platelets. It binds and displays peptides that are derived from proteins
( for ex. viral antigens) synthesized within the cell. CD8+ cytotoxic
cells can recognize peptides only presented as a complex with self
class I molecules.
• Class MHC II molecules are expressed on antigen presenting cells.
Class II molecules present exogenous antigens that are first
processed in the phagolysosomes. CD4+ can recognize peptides
presented as a complex with self class II molecules.
Nobel prize-2011 in
Phisiology and Medicine
Prof R.Steinman for dendritic
cells investigation

lmmunobiology : the immune system in health

and disease /
Charles A. Janeway, Jr. . [et al.].—5th ed.
lmmunobiology : the immune system in health and disease /
Charles A. Janeway, Jr. ... [et al.].—5th ed.
 Spleen
Red pulp – RBC destruction

White pulp
• Periarteriolar lymphoid
sheath _ T lymphocytes
• Follicles_B lymphocytes

lmmunobiology : the immune system in health and disease /

Charles A. Janeway, Jr. ... [et al.].—5th ed.
 NB!

• Spleen collects antigen from the blood

• Lymph nodes collects antigen from sites of

infection of tissues
 Humoral immune response
• Humoral immunity is mediated by antibodies,
which are produced by plasma cells deriving
from B lymphocytes
• It eliminates extracellular microbes and microbial
toxins:
neutralization,
opsonization,
complement system activation
• Antibodies : IgA, IgE, IgD, IgG, IgM
Pathophysiology, 8th ed, Editor CM Porth, 2009
• Activation of naÏve T cells requires 2
independent signals
1.Binding of peptid-MHC complex by T cell
receptor
2.Co-stimulatory signal delivered by the same APC
• Cytotoxic cells requires:
1. Activation by dendritic cell
2. Requires presence of CD4Tcells
TH2 drives B cells to differentiate to plasma cells
and produce Ig
H+E Myocarditis virosa

H+E

CD3 CD68 CD20

Infarctus myocardii
non specific immune response
 Immune granulomas
• Certain microorganisms having been
phagocytosed by macrophages avoid
intracellular killing and survive
• In such case T helpers (TH1) are
producing gamma interferon or other
macrophage activating factor
• Immune granuloma will be formed in
places where persistent antigen or toxic
materials occurs
 Immune granuloma
Composed of
Epitheliod cells – derived from macrophages
Giant cells – formed by fusion of macrophages
(epithelioid cells)
Necrosis – caused by lysosomal enzymes
released by macrophages or cytotoxic materials
as TNF
Lymphocytes
Other cells : can be also plasma cells, neutrophils,
eosinophils
Immune granuloma
Tubercle
 Formation of Immune Granulomas
induce:
• Mycobacterium tuberculosis
• Treponema pallidum
• Mycobacterium leprae
• Yersinia pseudoturbeculosis
• Echinococcus
• Foreign body granuloma (foreign body
giant cells – non Langhans type giant
cells)