1. General Pathology
Lecture/4
Immunity &Hypersensitivity
By
Associate Professor
Dr. Wadhah Mahdi Al-Badir

2. • Allergen: An antigen that has the capability of inducing IgE rather than IgG
or A production in an individual, resulting in an allergic response.
• Allergy: A largely IgE-mediated, inflammatory response to non-pathogenic
antigens resulting in pathological changes that may be damaging to the
host.
• Allogeneic: Term referring to genetically different members of the same
species.
• Allograft: A tissue graft between two members of the same species who
are not genetically identical
• Atopy: Usually used synonymously with allergy. It is used to describe IgE
mediated hypersensitivity responses.
• Autograft: Transplantation of tissue from one area to another on the same
• individual.
• Autoimmunity: An immune response to self antigens which may be
confined to a particular tissue or may be expressed systemically or
throughout the body. Such a response may have a range of pathological
effects resulting in autoimmune disease.

3. • Accessory cell: Term used for a cell (often an antigen presenting cell), which plays a
B lymphocyte (B cell): Mature products of the lymphoid progenitor cell that
• when stimulated by antigen may proliferate and differentiate into memory
cellsvital role in a specific immune response but cannot by itself mediate the same
Antibody-dependent cellular cytotoxicity (ADCC): Cells expressing foreign
antigen (e.g. viral antigens) become the target of antigen-specific antibodies.
These antibody-labelled target cells may then be destroyed by specialised killer
cells (including some large granular lymphocytes and macrophages) which have
receptors for the Fc part of the antibody (Fc receptors, FcR) and bind to the
target cell.
Antigen-presenting cell (APC): Cells that express molecules coded for by the
Class II genes of the major histocompatibility complex (MHC). They are
capable of processing and presenting antigen to T cells. APC include dendritic
cells, macrophages and B lymphocytes
B lymphocyte (B cell): Mature products of the lymphoid progenitor cell that
when stimulated by antigen may proliferate and differentiate into memory cells or
terminally differentiated plasma cells, which secrete antibody of the same
specificity as that on the originally activated parent cell.

4. Table /Characteristics that distinguish T from B lymphocytes
Characteristic Tcells B cells
Cell type Mononuclear Mononuclear
leukocyte/lymphocyte leukocyte/lymphocyte
Membrane molecules that Tcell antigen receptor Immunoglobulin/CD79a/b
Allow binding of antigen (TCR)/CD3 B cell antigen receptor
^ the antigen receptor (BCR)
Characteristic surface CD3, CD4 or CD8 Membrane
Membrane molecules Immunoglobulins
(mIg), CD19, CD20, CD40
Chief secretory products Lymphokines Antibodies

5. CELLS AND TISSUES OF THE IMMUNE SYSTEM 3
Figure 1.1 Representation of the developmental lineage of immunologically active cells

6. Figure 1.4 Antibody-dependent cellular cytotoxicity
In a virally infected cell, some of the viral proteins are expressed on the cell membrane allowing
virus-specific antibodies to bind to them. A killer cell can attach to this antibody using its Fc
receptor and is thereby activated and kills the virally infected target cell. This activity is known as
antibody-dependent cellular cytotoxicity (ADCC).

7. • Antigenic determinant: That part of an antigen which binds to antigen-binding
sites on the T or B cell antigen receptors. Also known as an epitope. Complex
antigens may have many different antigenic determinants or epitopes, each of
which can be recognised by different T or B cells.
• Antigen processing: The pathways (endogenous or exogenous) by which large
molecules are broken down within antigen presenting cells so that they can associate
with the products of the major histocompatibility complex genes and be
presented on the surface of the antigen-presenting cell.
• Carrier: A large molecule, which when attached to a smaller, non-immunogenic
molecule (hapten) allows the latter to stimulate an immune response.
• Cell-mediated cytotoxicity: The killing of another cell by an effector cell (e.g.
cytotoxic T cell, natural killer cell, macrophage).
• Cell-mediated immunity (CMI): All those immune responses in which antibody
plays little or no part. Largely mediated by T cells, macrophages and NK cells.
• Chemotaxin: A chemical capable of attracting cells through binding of specific
receptors on the cell surface and promoting their chemotaxis.
• Chemotaxis: The directed migration of cells up a concentration gradient of an

8. Inflammation versus Infection/ protection x invasion
• Inflammations either A. acute, B. chronic
• Changes in acute inflammation include
1.vascular events (hemodynamic& inc permeability)
2.cellular events (leukocytes exudates& phagocytosis)
• Components of immune system
1. Innate, natural immunity. Non specific, No Ag specificity
A).humoral ; complement system.
B). cellular; by PMNs, Macrophages, natural killer cells, NK
2. Adaptive immunity , specific.; Ag specific
A).humoral; Ab formed by B lymphocytes
B). cellular mediated by T lymphocytes forming cytokines
• Lymphocytes appear morphologically homogenous group, but functionally are of 2
major types B.-lymphocytes which differentiate into plasma cells Abs production
& T- lymphocytes proliferate in contact with appropriate Ag, after that accessory cells
(PMNs&macrophages) play critical role in completion of the immunological reaction.
These 2 types can be only differentiated by immunological methods,B cells by specific
Ab secretion, T cells by surface molecule, monoclonal Ab according to cluster differen –
tiation(CD)

9. Macrophages are monocytes & tissues macrophages;Their functions are:
1. Ag recognition & presentation to B &T lymphocytes
2. Phagocytic action due to presence of surface receptor for Fc fragment of IgG&C3
complement
3. IL-1 production play a role in B&T cells differentiation.
4. Lysing action on tumor cells by toxic metabolites.
5. As effector cells in cell mediated immunity e.g. delayed hypersensitivity reaction.
Act as mediator of inflammation in release ot PGs ,,activation of coagulation factors&
in secretion of acute phase reactant proteins by the liver
• -------------------------------------------------------------------------------------------------------
• Human Leucocyte Antigen(HLA) System
It is not a component of Immunity system, but regulate it& play role in tissue matching
and transplantation, most transplantation genes are present in ch.6of all nucleated
cells of the body& platelets called Major Histocompatability Complex(MHC) or (HLA)
complex on loci A,B,C&D on P arm of ch 6 w marked variation in allelic gene in each
locus,so it is highly polymorphic
MHC divided into
1.Class I MHC Ag have loci as HLA A,B&C. CD8 lymphocytes carry receptor for Class I
HLA Ag and used to identify it

10. MHC
2. Class II MHC Ag has single locus HLA D w further 3 loci DR.DQ,DP..It is identified byB
cells&CD4+T or T helper cells.
3.ClassIII Ag: some component of complement system C2,C4.codedon HLA complex Ag ,it
doesn't associate w HLA expression(useless in T matching).The polymorphism of Class I&II by
numbered loci eg.HLA-A1,A2..etc.
Roles of HLA complex in
1) Organ transplantation 2)regulation of immune system, humoral & cellular immunity
A) I Ag regulates function of cytotoxic cells (CD8+} eg. Viral infection.
B) II Ag regulates function of helper T cells(CD 4)
3)Association of disease w HLA
a. inflam..ankylosing spondylitis
b. Autoimmune dis..Rheumatoid arthritis.
c. Inherited disorders of metabolism..idiopathic hemochromatosis
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Diseases of Immunity
Immunity = Resistance to protect the body
Hypersensitivity is interchangeable w allergy
Diseases of immunity are of 4 types

11. Diseases of Immunity
1. Immunodeficiency disorders: Primary ,or Secondary eg.AIDS.
2. Hypersensitivity Reactions an exagurated immune response leading to various types
of T injury.
3. Autoimmune diseases: failure to recognize self from non self( collagen diseases)
4. Possible immunity disorders: may be due to immunological disorder in their
etiopathogenesis eg. Amyloidosis.
Primary Immunodeficiency
1. Combined B & T cells and Igs (bone marrow disorders)
2. T cells defects, Thymic hypoplasia.
3. B cells defects, Ab deficiency diseases.
4. Common variable immunodeficiency,decrease Ab production.
Secondary immunodeficiency
1. Infections 2.cancer 3.lymphoid diseases 4.Malnutrition 5.sarcoidosis
6.Autoimmune disease 7.transplantation
AIDS /Acquired Immunodeficiency Syndrome
,A human T cell leukemia-lymphoma virus,a s cytopathic virus has tropism to CD4 T
lymphocytes causing lysis of cells..it is of two types HIV1&HIV2.the viron consists
of core protein p24&p18,2 strands of RNA & the enz. reverse transcriptase

12. AIDS
WHO definition: existence of at least 2 major signs w at least one minor sign
Major signs: 1)wht loss >10% of body wht, 2) ch. diarrhea >1m, 3)fever >1m.
Minor signs: 1) rec orapharyngeal candidiasis 2)persistant generalized
lymphadenopathy 3) persistent cough >1m
Mode of transmission; 1)sexual 75% 2) paranteral 25% 3) perinatal transmission
Virus isolated from; semen vaginal ,cervical secretion, breast milk, synovial ,pericardial
peritoneal and amniotic fluid
AIDS cannot transmitted by non sexual casual contact, or sharing household facilities.
Sterilization & disinfection: by usual chemical germicidal w low conc. As formaldehyde
5% , ethanol 70%,chlorine bleaching,gluteraldehyde2%.
Phases of AIDS are three
1. Acute HIV syndrome (3—12w) seroconversion illness.
a)viremia (high level) b)seroconversion in3-6 w(virus specific imm response),c) inc.
CD8+T cells, d) selflimited nonspecific viral infection(flue like).
2.Middle chronic phase (10—12 yr)competition bet HIV & immune system
a) Viremia b) ch stage ,duration depends on host imm syst, c) CD4+ T cells continue to
prolif but the end result is dec.in No ofCD4+T,d) CD8+T cell count remain high,
f) Clinically a stage of latency,(CDC stage II) or w constitutional sympt+persistant
gen.lymph (CDC stageIII)

13. AIDS. cont.
3)Final stage characterized by profound immunosuppression& onset of full-blownAIDS
w the following features a) marked inc in viremia,b) time fom inf to eull blown
stage is 7—10 yrs death.c)CD4+T cell count dec.(<200/ul),d)clinically the features
of 5 subgroups (CDC stage IV)
1.subgr.A constit sympt of fever>1m,wht loss>10% B Wht, ch diarrhea >1m.
2.Subgr B neurogenic disease( vir meningoencephalitis’aseptic meningitis,periph
neuropathy& AIDS dementia.
3. Subgr C secondary opportunistic inf.(viral,bact & fungal or parasitic)
4.Subgr D s econdary neoplasm; (Kaposi sar, HL&NHL,Burkitt lymphoblastoma,, prim
CNS lymphomas)
5. Subgr E: CD4+T cells<200 ,pul TB,& rec pneumonia.
Average survival at onset of stage 3=18—24 m.
PATHOLIGICAL CHANGES: morphological changes are stage dependent
1.Lymphoid tissues early,B cells hyperplasia(nonsp follicular hyperpl+ plaslacytosis in
medulla of LN
Full blown AIDS;universal lymphoid depletionappor inf&malig lymphoma
2.Wide spread apport inf
3.AIDs associated cancer,uterus vagina cervix anus
4.Neurological manifestations
5.AIDS nephropathy,segmental glomerulonephritis.

14. LAB DIAGNOSIS
1. initial testing forAb HIV by ELISA
2. Confirmation by Western blot OR immunofluorescent test.of 2 types
1) specific test, i.serologicaltest ELISA,Western blot,& immunofl.
Ii Ag detection tests using envelope&core pt of HIV by recombent DNA
technique
Iii.Virus isolation in culture
iv.Polymerasr chain reaction PCR
2)indirect tests ; iCD4&CD8 cells count,reversal CD4/CD8 ratio
ii.Lymphopenia iiiLN biopsy iv thrombocytopenia Vincrease
B2microglobulin.
AUTOIMMUNE DIDEASES

15. EXAMPLES
i.Systemic anaphylaxis
(antisera,drugs,sting)
ii.Local anphylaxis(hay fever,
br asthma,food allergy)
i.Autoim hemolytic an,ITP,
trasf reaction, eryth fetalis,
leucopenia, drug induced
ii. Mysth gravis, male sterility
iii. Tumor cells,parasites
i.ATS inj,farmer’s lung
ii.Glomerioneph, collagen dis,
sk dis,uveitis
Type IV I. Clasical delayed hypersensitivity i.tuberculin,TB,Tb leprosy,
(Cell mediated) mediated by CD4 + t lymphocytes typhoid, contact dermatitis
II.T cell mediated cytotoxicity by CD8+ ii virus infected cells,tumor

16. Autoimmune Diseases
Immune system fail to distinguish between self & non self,it is the opposite of immune
tolerance
immune tolerance is a normal phenomenon since fetal life, it is the ability to recognize
Self tissue antigens, Through
1. Clonal elimination of T lymphocytes