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1

Susceptibility

 

Immunity

 

Innate immunity

 

Adaptive immunity

Lack of resistance to a disease

 

Ability to fight off a disease

 

Defense against any pathogens

 

Resistance to a specific pathogen (immunity)

2


Physical vs Chemical

Physical - Prevention entry

 

Chemical - Substance in the body that inhibits microbial growth

3


Plasma vs Formed elements


Plasma - Fluid component

 

Formed Elements - Cellular component (Leukocytes) for both innate and adaptive immune system

4


Granulocytes vs Agranulocytes


Granulocytes

Basophil

Neutrophil aka polymorphonuclear leukocytes (PMN)

Eosinophil

 

Agranulocytes

Lymphocyte - NK (innate), T cells & B cells (adaptive)

Monocyte - when stimulated, leaves blood stream and enters tissues and turns into macrophages

5


Phagocytosis


Clears away debris (dead cells & denatured proteins)

 

Removes foreign materials (microbial infection)

 

Diapedisis - phagocytes squeeze b/t endothelial cells

6


Fixed vs Free macrophages


Fixed - do not leave tissures

Kupffer's cells - Liver macrophages

Alveolar - Lung macrophages

Microglial Cell - Nervous system

 

Free - wanderers

Roams around and gather at the site of infection/inflammation

7


Inflammation


Redness

Edema

Pain

Heat

Loss of Function

8


Complement System


over 30 proteins

produced in liver circulates all over

Not adaptavle and does not change

Destroys microbes by

  • Cytolysis
  • Inflammation
  • Phagocytosis

Inactive until split into fragments

i.e. C1, C2, C3

 

9


How does the innate immune system recognize foreign materials such as bacteria?

Toll-like receptors (TLR) attaches to the Pathogen-associated molecular patterns (PAMP)

 

TLR induces cytokines - regulates intensity and duration of immune responses

 

Innate Immue

  • TLR on host cells recognizes & attaches to the PAMP of bacterial cell
  • TLR induces cytokines - sends out signal

 

Adatptive Immune system

  • APC (b cells, macrophages, dentritic cell)
  • Engulf pathogen
  • Remenants of pathogen is presented on the surface by MCH I and MCH II
  • MCH I attracts T Cytotoxic cell via TCR - CD8 - recognizes infected cells aka target cells and sends signal (perforin & granzymes) for apoptosis.
  • MCH II attracts TCR (t cell receptors) on the T-helper cell - CD4 - and binds to B cells and release cytokines to activate macrophage to engulf pathogen. Also, B-cells starts to divide into plasma cells -> antibodies & memory cells (clonal expansion)

 

10


Bone Marrow


Produces Lymphocytes

  • One group of lymphocytes migrates to thymus - creating T-cells (Cellular)

 

  • Second group matures in bone marrow - creating B-cells (Humoral)

 

 

 

11


Humoral vs Cellular Immunity

Humoral

Blood, phlegm, black bile, yellow bile

B cells (Bone Marrow), carries Ig.

  • Bursa of Fabricius in Birds
  • produces antibodies
  • divides into 2 daughter cells (plasma & Memory) which synthesize and secretes antibodies (clonal expansion)
  1. Plasma cells - produces antibodies
  2. Memory cells - Long lived and secondary response cells.
  • Activation typically requires T helper cell (T dependent antigen)
  • Fragments combined with MHC (major histocompatibility Complex)
  • Antigen processing & Presentation, marks for destruction


Cellular

T cells (Thymus)

  • Responds to antigen by T cell receptors (TCR)
  • requires antigen presenting cells (APC) by MCH class I or II
  • T helper cells helps humoral immunity
  • T cytotoxic cell can become cytotoxic T lymphoctye (CTL) and recognize/destroy infected cells/cancer cels
  • classified by glycoproteins
  • T helper cells are CD4 (Binds to MHC Class II on b cells & antigen presenting cells
  • T cytotoxic cells are CD8 (binds to MHC class I)
  • Target cells are self carrying endogenous antigens
  • CTLs recognizes Antigen & MCH I which induces apoptosis to the target cell and releases perforin/granzymes

 

12


How does innate immune system recognize foreign materials/ bacterias?

 

How does antibodies recognize antigens?

Host Toll like receptors (TLR) attaches to the pathogen assoiciated molecular patterns (PAMP)

 

Epitopes

13

Antigens

Proteins or polysaccharide

  • Capsule
  • Cell wall
  • Flagella
  • Fimbriae
  • Toxin
  • Viral Coat

Not all antigens are from microbes, could be pollen, egg whites, Surface of blood cells, Serum from another species or surface transplanted tissue/organs

 

14


Epitope vs Hapten


Epitope - How antibodies recognize antigens

 

Hapten - Needs to bind with carrier molecue = Hapten-carrier conjugate

 

15


Antibody


Globular protein

aka Ig

Has 2 identical site that binds to epitopes (antigen binding site)

Has variable region and constant region

Stem is Fc region

16

IgG

IgM

IgA

IgD

IgE

IgG - fix complement, most abundant, enhances phagocytosis, nuetralizes toxins/viruses, protects fetus and newborn

 

IgM -  Fix complement, Agglutinates microbes, first to respond infection

 

IgA - Mucosal protection, in secretions

 

IgD - On B cells, initates immune response

 

IgE - On mast cells, basophils and blood, Allergic reactions, lysis parasites, least abundant

17

Antibody binding to antigen


Agglutination

Opsonization - enhances phagocytosis by coating antigen w/ antibody

Neutralization - blocks adhesion of bacteria/virus to mucosa

Activation of complement - causes inflammation & cell lysis

Cytoxocity - destruction of target cell by macrophages, eosinophils, NK cells

18


Precipitation Reactions


involves soluble antigens/antibodies, IgG or IgM

 

Antibody binds to antigens forming lattice structure and cloudy precipitate

 

Zone of equivalence: visible precipitate

19


Complement fixation


when antibody binds to antigen has the ability to start a cascade of events carried out by complement proteins

20


ELISA


Enzyme Linked Immunosorbent Assay

Enzyme linked to antibody as indicator

ie. pregnancy test

 

Direct ELISA

  • Antibody in well
  • Patient sample is added
  • Complementary antigen binds to antibody
  • Enzyme linked antibody is added and binds to antigen
  • Enzyme substrate is added and reaction produces color

Indirect ELISA

  • Antigen in well
  • Patient serum is added
  • Complementary antiboy binds to antigen
  • Enzyme linked anti HISG is added and binds to antibody
  • Enzyme substrate is added and reaction causes color

 

21


Hypersensitivity Reactions


Response to antigens (allergens) leading to damage

 

Anaphylatic

Cytotoxic

Immune comples

Cell mediated (delayed type)

 

22

Anaphylatic type I

IgE attaches to mast cells and basophils

Antigen binds to 2 adjacent IgE

Mast cells & basophils undergo degranulation and releases:  Histamine, Leukotrienes, Prostaglandin

serves as chemotactic agents

attracts neutrophils and eosinophils causing inflammatory symptoms:

  • swelling
  • distention of capillaries
  • Increased mucous secretion
  • Involuntary smooth muscle contraction

 

23


Anaphylactic Type I

 

Systemic vs Localized


Systemic

  • dramtic drop in blood pressure
  • Cirulatory collapse and death in minutes

 

Localized

  • Ingested or inhaled allergens
  • Hives, Hay fever, asthma

 

 

24

 Anaphylatic Type IV


Delayed type hypersensitivity due to T cells

Delay due to the time required for T cells to migrate to site of allergen

 

Cytokines attracts macrophages and TC cells and initiates tissue damamge

 

25


HIV


Transmission via needle sharing is efficient = 0.67% risk

80% of transmission via sexual intercourse

Env - comprised of gp120 & gp41. 

GP120 binds to CD4 on T cell surface

Coreceptor:  CCR5

GP41 pulls viral envelope closer proximity with plasma membrane triggering fusion allowing viral core to enter cell.

Genomic RNA is reverse transcribed by viral reverse transcriptase

vDNA is imported into host nucleus and integration takes place by viral enzyme, integrase

 

26


Acute HIV


First serveral weeks of HIV infection

aka primary phase

large quantities of virus are produced

 

symptoms

  • flu like
  • fever
  • sore throat
  • malaise
  • swollen lymph nodes
  • headache
  • diarrhea

 

27

Symptomatic HIV stage


When CD4 T cells fall below 400 cells per 1 mL of blood

(normal: 500)

 

Signs

  • Weight loss
  • fever
  • fatigue
  • loss of appetite
  • diarrhea
  • headaches
  • swollen lymph nodes

28


Advnaced HIV Stage


AIDS

CD4 T cells falls below 200 per 1mL of blood

Onset of opportunistic infections

HAART: Highly Active Antiretroviral Therapy is used.  Helps suppress the virus

 

29


Restriction Enzymes


Cuts DNA to specific sequences

aka restriction sites

 

30


Plasmid Vector


Plasmid can be inserted into living cell - Transformation

 

Vector must have a gene that express a selectable phenotype i.e. antibiotic resistance to verify that the cell taken the vector