Pathophysiology_of_imunitygooliiiiat.ppt

This power point is very important for both learners and teachers

1. Pathology of immunity

2. The immune system (IS)
Main physiologic role:
- primary role of IS is to discriminate self from
nonself and to eliminate the foreign substance

- finely tuned network that protects the host
against forein antigens, particularly infection
agents
Pathophysiologic changes of immune system:
- the mentioned network can be broken down,
causing IS to react inappropriatelly

3. Hypersensitivity
1) Exaggerated activity against environmental
antigens (allergy)
2) Misdirected activity against host’ s own cells
(autoimmunity)
3) Activity directed against benefitial foreign tissues,
e.g. transfusion, transplants (isoimunity)
Hyposensitivity
1) Activity insufficient for protection of the body
(immune deficiency)
Main forms of inappropriate reactions of
immune system

4. Types of hypersensitivity
– are differentiated by the sorce of the antigens
against which the hypersensitivity is directed
A)Allergy – it has two facets:
a) immune response which is benefitial
b) hypersensitivity which is harmful
Definition: Deleterious effects of hypersensitive
reactions to environmental (aerogenous)
antigens expressed by disease
B) Autoimmunity
– disturbance in the immunologic tolerance of
self-antigens
– immune system reacts against self –antigens
by creating autoantibodies- autoimmune diseases

5. Most diseases related to hypersensitivity
evolve because of interaction of at least
3 variables:
a) an original insult which alters immunologic
homeostasis
b) the individual’s genetic makeup which determins
susceptibility to the effects of the insult
c) immunologic process that amplyfies the insult

6. Mechanisms involved in development different
types of hypersensitivity
Type I: IgE – mediated allergic reactions
Type II: Tissue specific reactions
Type III: Immune-complexes mediated reactions
Type IV: Cell-mediated reactions
Immediate hypersensitivity reactionsImmediate hypersensitivity reactions – – within minutes
Delayed hypersensitivity reactionsDelayed hypersensitivity reactions – within sevral hours
and days from the time of exposure to antigen
Time corse of hypersensitivity reactions

8. Type I hypersensitivity
1) Anaphylaxis – rapid and severe reaction developed
within minutes
a) systemic (generalised):
itching, erithema, womiting, abdominal cramps,
diarhea, breathing difficulties, laryngeal edema,
angioedema, vascular collapse, shock, death
b) cutaneous (localised):
signes of local inflammation

9. 2) IgE – mediated reactions
Characteristics:Characteristics:
- production of antigen – specific IgE after exposure
to antigen
- the most common alleregic reactions are mediated
by IgE
- antigens which cause allergic reactions are called
allergens
3) Atopy
Characteristics:Characteristics:
- it expresses the proneness to allergy
- the atopic persons produce more than normal IgE
and have more Fc receptors on their mast cells
- subtle defect in T-Ly function (e.g. deficiency in
IgE-specific supressor cells) may account for
hightened IgE production

12. Type II hypersensitivity
Characteristics:Characteristics:
- destruction of target cells through the action of
antibodies against an antigen on the surface of cell
membrane
ExplanationExplanation::
- in addition to HLA system most tissue have tissue
specific antigens (TSA) = expressed only on the
plasma membrane of certain type of cells
- because of limited distribution of TSA, type II disease
are limited to those tissue and organs that expresse
the particular antigen

13. Mechanisms involved in cells destruction
in type II hypersensitivity
1) – Antibody (Atb) is bind to TSA
– Atb „fixes“ complement  initiation of
complement cascade (CCD)  lysis of the cell
- e.g. autoimmune hemolytic anemia, transfusion
reaction to donor blood cells
2) – Atb is bind to TSA
– macrophages are able to recognize and bind the
opsonised cells  phagocytosis  lysis of cells

14. 3) – Atb is bind to TSA
– Fc receptors on cytotoxic cells are able
to recognize the antigen on the target cells 
 binding of cytotoxic cells on target cells 
 cytotoxic cells release of toxic substances 
 lysis of target cells
4) – Atb is bind to TSA
– Atb occupy and alters receptors on target cells
 blockade of normal ligands for these receptors 
 changes in cellular functions
- e.g. Grave’s disease

15. Type III hypersensitivity
Characteristics:Characteristics:
- antigen-antibodies complexes (ANt-ATb-C) are createdantigen-antibodies complexes (ANt-ATb-C) are created
in circulating blood in circulating blood  deposition of ANt-Atb-C in the deposition of ANt-Atb-C in the
vessel wall or in other extracellular tissuesvessel wall or in other extracellular tissues
- this reaction is not organ – specificthis reaction is not organ – specific
- harmful effect of ANt-Atb-C is caused by activation of harmful effect of ANt-Atb-C is caused by activation of
complement and by attempt of NE-Le to ingest complement and by attempt of NE-Le to ingest
these complexes these complexes  releasing of lysosomal enzymes releasing of lysosomal enzymes 
 tissue damage tissue damage

16. Diseases caused by type III hypersensitivityDiseases caused by type III hypersensitivity
• Serum sickness (called according the foreign serum
used and symptoms and signs development)
- general deposition of immune-complexes in blood
vessels, joints, kydney
- symptoms and signs: fever, enlarged lymphonodes,
rash, pain
• Rayanaud’s phenomenon:
- temperature-dependent deposition of immune
complexes in peripheral vessel (cryoglobulins)
• Arthus phenomenon:
- example of localised immune-complexes-mediated
inflammatory response. It developes due to repeated
local exposure to exogenous antigen which reacts
with preformed antibodies in the vessel wall

17. Type IV hypersensitivity

Characteristics:Characteristics:
- it is mediated by specifically sensitised T-Ly- it is mediated by specifically sensitised T-Ly
- it does not involve antibodiesit does not involve antibodies
- types of sensitised Ly ivolved in reaction:types of sensitised Ly ivolved in reaction:
- cytotoxic T-Ly- cytotoxic T-Ly
- lymphokine-producing T-cells- lymphokine-producing T-cells
Pathologic processes induced Pathologic processes induced
by type IV hypersensitivity by type IV hypersensitivity
- - graft rejection - tumor rejection graft rejection - tumor rejection
- tuberculin reaction - reaction to contact - tuberculin reaction - reaction to contact
with e.g. metals or ivy with e.g. metals or ivy

19. Diseases caused by type IV Diseases caused by type IV
hypersensitivityhypersensitivity
•• Rheumatoid arthritisRheumatoid arthritis - antigen - antigen is type II collagen in
joint tissue
• Hashimoto’s disease - antigen is protein present in
thyroid cells
• Diabetes mellitus-type 1- antigen is a protein of the
-cells of Langerhans islets

20. Pathogenesis of hyposensitivity
This disorder results from deficiciences in immunity
and leads to development of different clinical
manifestations. These manifestations are the result of
impaired function of one or more components of the
immune system – e.g. B-cells,T-cells, phagocytic cells,
complement
Classification:Classification:
1) Congenital (primary) immune deficiency1) Congenital (primary) immune deficiency
- due to genetic disorders- due to genetic disorders
2) Acquired (secondary) immune deficiency2) Acquired (secondary) immune deficiency
- due to another illness-e.g. cancer, viral infection - due to another illness-e.g. cancer, viral infection
- due to physiologic changes- e.g. ageing- due to physiologic changes- e.g. ageing

21. Diseases caused by immune deficiencyDiseases caused by immune deficiency
• Primary T-cell defects
- severe combined immune deficiency (SCID)
- Di George syndrome (thymic aplasia or hypoplasia)
• Primary B-cells defects
- agammaglobulinemia
- selective IgA, IgM, IgE deficiencies
• Phagocytic defects
a) quantitative defects -e.g. congenital splenic aplasia,
Sickle cell anemia,
congenital neutropenia
b) chemotactic defects – lazy leucocyte sy.
c) microbicidal defect – chronic granulomatous disease
– myeloperoxidase deficiency
• Complement defects

23. ImmunoDefiency
Syndromes (-IDS)
•PRIMARY (GENETIC) (P-
IDS?)
•SECONDARY
(ACQUIRED) (A-IDS)

24. PRIMARY
•CHILDREN with repeated, often severe
infections, cellular AND/OR humoral
immunity problems, autoimmune defects
•BRUTON (X-linked agammaglobulinemia)
•COMMON VARIABLE
•IgA deficiency
•Hyper -IgM
•DI GEORGE (THYMIC HYPOPLASIA) *22q11.2
•SCID (Severe Combined Immuno Deficiency)
•….with thrombocytopenia and eczema
(WISKOTT-ALDRICH)
•COMPLEMENT DEFICIENCIES

25. ADA=
ADENOSINE
DEAMINASE

26. Examples of Infections in Immunodeficiencies
Pathogen Type T-Cell-Defect B-Cell Defect
Granulocyte
Defect Complement Defect
Bacteria Bacterial sepsis Streptococci,
staphylococci,
Haemophilus
Staph,
Pseudomo
nas
Neisserial
infections,
other
pyogenic
infections
Viruses
Cytomegalovirus,
Epstein-Barr virus,
severe varicella,
chronic infections
with respiratory and
intestinal viruses
Enteroviral
encephalitis
Fungi and
parasites
Candida, Pneumocystis
carinii
Severe intestinal
giardiasis
Candida,
Nocardia,
Aspergillus
Special featuresAggressive disease with
opportunistic pathogens,
failure to clear infections
Recurrent
sinopulmonary
infections, sepsis,
chronic meningitis

27. (A)IDS(SECONDARY IDS)
•Etiology: HIV
•Pathogenesis: Infection, Latency,
Progressive T-Cell loss
•Morphology: MANY
•Clinical Expressions: Infections,
Neoplasms, Progressive Immune Failure,
Death, HIV+, HIV-RNA (Viral Load)

28. EPIDEMIOLOGY
•HOMOSEXUAL (40%, and
declining)
•INTRAVENOUS DRUG
USAGE (25%)
•HETEROSEXUAL SEX (10%
and rising)

29. ETIOLOGY

30. PATHOGENESIS
ATTACHING BUDDING

31. PATHOGENESIS
EARLY BUDDING

32. PATHOGENESIS
LATE BUDDING

33. PATHOGENESIS
MATURE NEW VIRIONS

34. REVERSE TRANSCRIPTASE
•The enzyme reverse transcriptase
(RT) is used by retroviruses to
transcribe their single-stranded
RNA genome into single-stranded
DNA and to subsequently construct
a complementary strand of DNA,
providing a DNA double helix
capable of integration into host cell
chromosomes.

35. PATHOGENESIS

36. PATHOGENESIS
1) PRIMARY INFECTION
2) LYMPHOID INFECTION
3) ACUTE SYNDROME 4-8
weeks)
4) IMMUNE RESPONSE
5) LATENCY
6) AIDS

38. GENERAL IMMUNE
ABNORMALITIES
•LYMPHOPENIA
•DECREASED T-CELL
FUNCTION
•B-CELL ACTIVATION,
POLYCLONAL
•ALTERED
MONOCYTE/MACROPHAGE
FUNCTION

39. INFECTIONS
•Protozoal/Helminthic:
Cryptosporidium, PCP (Pneumocystis
Carinii (really Jiroveci) Pneumonia),
Toxoplasmosis
•Fungal: Candida, and the usual 3
•Bacterial: TB, Nocardia, Salmonella
•Viral: CMV, HSV, VZ (Herpes Family), HPV

40. PCP

41. CRYPTOSPORIDIUM

42. CASEATING GRANULOMA

43. CANCERS of AIDS
•KAPOSI SARCOMA (Herpes-8)
•B-CELL LYMPHOMAS
•CNS LYMPHOMAS
•CERVIX CANCER, SQUAMOUS
CELL (HPV)